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Objective To assess the effect of filgotinib, which preferentially inhibits Janus kinase 1 (JAK1), on MRI measures of structural change in the SI joint in patients with active AS in the TORTUGA trial. Methods Adults with active AS and inadequate response/intolerance to two or more NSAIDs were randomized 1:1 to filgotinib 200 mg (n = 58) or placebo (n = 58) once daily for 12 weeks. In this post hoc analysis, T1-weighted MRI scans of the SI joint were evaluated by two independent readers using Spondyloarthritis Research Consortium of Canada (SPARCC) Sacroiliac Joint Structural Score (SSS) definitions for erosion, backfill, fat metaplasia and ankylosis. Correlations between SPARCC SSS and improvement in clinical outcomes were also assessed. Results MRI scans from 87 patients (48 filgotinib, 39 placebo) were evaluated. At baseline there were no notable differences between filgotinib and placebo for any MRI structural lesion types. From baseline to week 12, filgotinib was associated with a significant reduction in SI joint erosion score (P = 0.02) and an increase in backfill score (P = 0.005) vs placebo, with no significant between-group differences for ankylosis (P = 0.46) or fat metaplasia (P = 0.17). At week 12, the change in SPARCC MRI SI joint inflammation scores correlated positively with erosion scores but negatively with backfill scores. Conclusion The significant changes in MRI structural lesions induced by filgotinib in the SI joint by week 12 demonstrate that tissue repair can be observed very soon after starting treatment with a JAK1 preferential inhibitor. This could have prognostic implications for development of ankylosis. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT03117270

ObjectiveTo characterise safety of the Janus kinase-1 preferential inhibitor filgotinib in patients with moderately to severely active rheumatoid arthritis.MethodsData were integrated from seven trials (NCT01668641, NCT01894516, NCT02889796, NCT02873936, NCT02886728, NCT02065700, NCT03025308). Results are from placebo (PBO)-controlled (through week (W)12) and long-term, as-treated (all available data for patients receiving ≥1 dose filgotinib 200 (FIL200) or 100 mg (FIL100) daily) datasets. We calculated exposure-adjusted incidence rates (EAIRs)/100 patient-years filgotinib exposure (100PYE) for treatment-emergent adverse events (TEAEs).Results3691 patients received filgotinib for 6080.7 PYE (median 1.6, maximum 5.6 years). During the PBO-controlled period, TEAEs, including those of grade ≥3, occurred at comparable rates with filgotinib or PBO; long-term EAIRs of TEAEs grade ≥3 were 6.4 and 7.6/100PYE for FIL200 and FIL100. EAIRs for deaths were 0.6/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 0.5 and 0.3/100PYE for FIL200 and FIL100. EAIRs for serious infection were 3.9, 3.3 and 2.4/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 1.6 and 3.1/100PYE for FIL200 and FIL100. EAIRs for herpes zoster were 0.6, 1.1, and 1.1/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 1.8 and 1.1/100PYE for FIL200 and FIL100. EAIRs for major adverse cardiovascular events were 0, 1.7 and 1.1/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 0.4 and 0.6/100PYE for FIL200 and FIL100. No venous thromboembolism occurred during the PBO-controlled period; long-term EAIRs were 0.2 and 0/100PYE for FIL200 and FIL100.ConclusionsOver a median of 1.6 and maximum of 5.6 years of exposure, safety/tolerability of FIL200 and FIL100 were similar, with a lower incidence of infections with FIL200 among the long-term, as-treated dataset.

Objectives To assess the effects of filgotinib on inflammatory and structural changes at various spinal locations, based on MRI measures in patients with active AS in the TORTUGA trial. Methods In the TORTUGA trial, patients with AS received filgotinib 200 mg (n = 58) or placebo (n = 58) once daily for 12 weeks. In this post hoc analysis, spine MRIs were evaluated using the Canada–Denmark (CANDEN) MRI scoring system to assess changes from baseline to week 12 in total spine and subscores for inflammation, fat, erosion and new bone formation (NBF) at various anatomical locations. Correlations were assessed between CANDEN inflammation and clinical outcomes and Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores and between baseline CANDEN NBF and baseline BASFI and BASMI scores. Results MRIs from 47 filgotinib- and 41 placebo-treated patients were evaluated. There were significantly larger reductions with filgotinib vs placebo in total spine inflammation score and most inflammation subscores, including posterolateral elements (costovertebral joints, transverse/spinous processes, soft tissues), facet joints and vertebral bodies. No significant differences were observed for corner or non-corner vertebral body inflammation subscores, spine fat lesion, bone erosion or NBF scores. In the filgotinib group, the change from baseline in the total inflammation score correlated positively with the SPARCC spine score. Baseline NBF scores correlated with baseline BASMI but not BASFI scores. Conclusions Compared with placebo, filgotinib treatment was associated with significant reductions in MRI measures of spinal inflammation, including in vertebral bodies, facet joints and posterolateral elements. Trial registration ClinicalTrials.gov (https://clinicaltrials.gov), NCT03117270.

ObjectiveThe long-term safety and efficacy of filgotinib (from phase II studies), with or without methotrexate (MTX), for the treatment of patients with rheumatoid arthritis was assessed in DARWIN 3, a long-term, open-label extension study (ClinicalTrials.gov: NCT02065700).MethodsEligible patients completing the 24-week DARWIN 1 (filgotinib + MTX) and DARWIN 2 (filgotinib monotherapy) studies entered DARWIN 3, where they received filgotinib 200 mg/day, except for 15 men who received filgotinib 100 mg/day. Safety analyses were performed using the safety analysis set and the exposure-adjusted incidence rate (EAIR) of treatment-emergent adverse events (TEAEs) was calculated. Efficacy was assessed from baseline in the parent studies.ResultsOf 790 patients completing the phase II parent studies, 739 enrolled in the study. Through April 2019, 59.5% of patients had received ≥ 4 years of the study drug. Mean (SD) exposure to filgotinib was 3.55 (1.57) years in the filgotinib + MTX group and 3.38 (1.59) years in the filgotinib monotherapy group. EAIR per 100 patient-years of exposure for TEAEs was 24.6 in the filgotinib + MTX group and 25.8 in the filgotinib monotherapy group, and for serious TEAEs, the EAIR was 3.1 and 4.3, respectively. American College of Rheumatology 20/50/70 responses among patients remaining in the study could be maintained through 4 years, with 89.3%/69.6%/49.1% of the filgotinib + MTX group and 91.8%/69.4%/44.4% of the monotherapy group maintaining ACR20/50/70 responses, respectively, based on observed data.ConclusionFilgotinib was well tolerated with a 4-year safety profile comparable to that of the parent trials, both in patients receiving combination therapy with MTX or as monotherapy.

Aims The SELECTION (NCT02914522) Induction Studies evaluated the efficacy/safety of filgotinib (FIL), a preferential JAK1 inhibitor, as induction therapy for patients (pts) with moderately to severely active ulcerative colitis (UC) who were biologic-naïve but failed conventional therapy (Induction Study A) or failed prior biologics (Induction Study B). Methods Pts were randomized 2:2:1 to once–daily FIL 200mg, FIL 100mg or placebo (PBO). The primary (clinical remission), key secondary (Mayo Clinic Score [MCS] remission, endoscopic remission, and histologic remission), and exploratory endpoints (MCS response and endoscopic improvement) were assessed at Week 10. Results In both studies, baseline demographics and disease characteristics were similar across treatment groups. In Study A, 659 pts were randomized and treated. Baseline mean MCS was 8.6 and 56% had a Mayo endoscopic subscore (ES)=3. A significantly higher proportion of biologic-naïve pts on FIL 200mg achieved clinical remission vs PBO and all key secondary endpoints (Table). In Study B, 689 pts were randomized and treated. Baseline mean MCS was 9.3 and 78% had ES=3. Prior treatment failures were: anti-TNF (86%), vedolizumab (52%) and both (dual-refractory; 43%). A significantly higher proportion of biologic-experienced pts on FIL 200mg achieved clinical remission vs PBO. In Studies A and B, a greater proportion of pts on FIL 200 mg achieved an MCS response and endoscopic improvement vs PBO. The rates of AEs, serious AEs and discontinuations due to AEs were similar across FIL and PBO groups during induction. In the PBO, FIL 100mg and FIL 200mg groups, serious infections occurred in 0.7%, 0.7% and 0.4% pts in Study A and 1.4%, 1.4% and 0.8% pts in Study B; H Zoster occurred in Conclusions SELECTION included a high proportion of dual-refractory pts, and pts with severe endoscopic disease. Both doses of FIL were well tolerated. Filgotinib 200mg was effective induction therapy for both biologic-naïve/-experienced pts with moderately to severely active UC. Funding Agencies None

BackgroundThe preferential Janus kinase-1 inhibitor FIL significantly improved signs and symptoms of RA in Phase 2 and 3 trials.1–5 FIL is approved for treatment of moderate to severe active RA in Europe and Japan. Integrated safety analysis of FIL with patient data through 2019 was presented at the 2020 ACR virtual meeting.6ObjectivesTo report updated, as-treated data from the FIL integrated safety analysis with increased study drug exposure.MethodsData were integrated from 2 Phase 2 (NCT01668641, NCT01894516), 3 Phase 3 (NCT02889796, NCT02873936, NCT02886728), and 2 long-term extension (LTE) (NCT02065700, NCT03025308) trials. Phase 2 and 3 LTE data were through Nov 2020 and Jan 2021, respectively. The as-treated analysis set included all available data for pts receiving ≥1 dose FIL 200 (FIL200) or 100 mg (FIL100), including those rerandomized to FIL for LTE. Exposure-adjusted incidence rates (EAIR)/100 patient-y exposure (PYE) of treatment-emergent adverse events (TEAEs; onset after first dose and no later than 30 days after last dose or new drug first dose date −1 day) and TEAEs of special interest (AESIs) are presented.Results3691 pts received FIL200 or FIL100 for 8085.1 PYE (median 2.2, maximum 6.8 y). In the as-treated set, 61% of FIL200 and 45% of FIL100 pts received FIL for ≥2 y, 19% and 5% for ≥3 y, and 11% and 0.5% for ≥4.5 y, respectively. EAIR for TEAEs was higher with FIL100 than FIL200; EAIRs for deaths were 0.5 and 0.3 for FIL200 and FIL100 (Figure 1). Incidences of infections and serious infections were numerically greater for FIL100 vs FIL200, while EAIRs for other AESIs were comparable between doses (Table 1). EAIRs for AESIs tended to decrease since the previous update, except for venous thromboembolism (total FIL 0.1 to 0.2) and malignancies excluding NMSC (total FIL 0.5 to 0.6).Table 1.TEAEs of special interest, as-treated setTEAE, n (%) and EAIR per 100 PYE (95% CI)FIL 200 mgn=2267PYE=5302.5FIL 100 mgn=1647PYE=2782.6Total FILN=3691PYE=8085.1Infectious AEs1206 (53.2)747 (45.4)1927 (52.2)EAIR21.1 (19.7, 22.5)30.2 (26.8, 34.0)21.0 (19.9, 22.3)Serious infectious AEs80 (3.5)57 (3.5)137 (3.7)EAIR1.5 (1.1, 1.9)2.7 (1.9, 3.9)1.6 (1.3, 2.0)Opportunistic infections5 (0.2)4 (0.2)9 (0.2)EAIR0.1 (0, 0.2)*0.1 (0.1, 0.4)*0.1 (0.1, 0.2)*Active tuberculosis03 (0.2)3 (EAIR00.1 (0, 0.3)*0 (0, 0.1)*Herpes zoster84 (3.7)30 (1.8)114 (3.1)EAIR1.6 (1.2, 2.0)1.1 (0.8, 1.5)*1.4 (1.1, 1.7)Major adverse cardiovascular eventsa19 (0.8)14 (0.9)33 (0.9)EAIR0.3 (0.2, 0.5)0.5 (0.3, 0.8)*0.4 (0.2, 0.6)Venous thromboembolismb11 (0.5)4 (0.2)15 (0.4)EAIR0.2 (0.1, 0.4)*0.1 (0.1, 0.4)*0.2 (0.1, 0.3)*Atrial systemic thrombotic eventsa1 (1 (2 (EAIR0 (0, 0.1)0 (0, 0.3)0 (0, 0.1)Malignancy excluding NMSC32 (1.4)17 (1.0)49 (1.3)EAIR0.6 (0.4, 0.9)0.6 (0.4, 1.0)*0.6 (0.4, 0.8)NMSC15 (0.7)5 (0.3)20 (0.5)EAIR0.3 (0.2, 0.5)*0.2 (0.1, 0.4)*0.2 (0.2, 0.4)*Gastrointestinal perforations3 (0.1)1 (4 (0.1)EAIR0.1 (0, 0.2)*0 (0, 0.3)*0 (0, 0.1)**Except when any study had 0 event within the treatment, the Poisson model was not adjusted by study. PYE was defined as (last dose date − first dose date + 1)/365.25.aPositively adjudicated.bAdjudicated as deep vein thrombosis or pulmonary embolism.NMSC, nonmelanoma skin cancerConclusionWith 1 additional year of exposure since the 2020 report, FIL continues to be well tolerated with no new safety concerns emerging. EAIRs of TEAEs, including deaths, and AESIs remained stable or decreased since the 2020 report, except for slight increases in rates of NMSC and malignancies excluding NMSC. In the context of demonstrated efficacy, both FIL doses had an acceptable risk/benefit profile.References[1]Westhovens R et al. Ann Rheum Dis 2017;76:998–1008.[2]Kavanaugh A et al. Ann Rheum Dis 2017;76:1009–19.[3]Combe B et al. Ann Rheum Dis 2021;80:848–58.[4]Genovese MC et al. JAMA 2019;322:315–25.[5]Westhovens R et al. Ann Rheum Dis 2021;80:727–38.[6]Winthrop K et al. Arthritis Rheumatol 2020;72(suppl 10); abstract 0229.AcknowledgementsFunding for DARWIN 1 and 2 was provided by Galapagos NV, and funding for DARWIN 3, FINCH 1, 2, 3, and 4 was provided by Gilead Sciences, Inc., Foster City, CA. Funding for this analysis was provided by Gilead Sciences, Inc. The sponsors participated in the planning, execution, and interpretation of the research. Medical writing support was provided by Gregory Bezkorovainy, MA, of AlphaScientia, LLC, San Francisco, CA; and funded by Gilead Sciences, Inc., Foster City, CA.Disclosure of InterestsKevin Winthrop Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly and Co., Galapagos NV, Gilead Sciences, Inc., GlaxoSmithKline, Pfizer, Roche, Regeneron, Sanofi, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, and Pfizer, Yoshiya Tanaka Speakers bureau: Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol Myers Squibb, Eisai, Chugai, AbbVie, Astellas, Pfizer, Sanofi, Asahi-Kasei, GSK, Mitsubishi-Tanabe, Gilead Sciences, Inc., and Janssen, Consultant of: AbbVie, Ayumi, Daiichi-Sankyo, Eli Lilly, GSK, Taisho, and Sanofi, Grant/research support from: AbbVie, Asahi-Kasei, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, and Takeda, Tsutomu Takeuchi Speakers bureau: AbbVie, AYUMI, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Eli Lilly Japan, Gilead Sciences, Inc., Mitsubishi-Tanabe, Novartis, Pfizer Japan, and Sanofi, Consultant of: Astellas, Chugai, and Eli Lilly Japan, Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi Sankyo, Eisai, Mitsubishi-Tanabe, Shionogi, Takeda, and UCB Japan, Alan Kivitz Shareholder of: Amgen, Gilead Sciences, Inc., GlaxoSmithKline, Pfizer, and Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, and Sanofi, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, and Sanofi, Consultant of: AbbVie, Boehringer Ingelheim, Flexion, Genzyme, Gilead Sciences, Inc., Janssen, Novartis, Pfizer, Regeneron, Sanofi, and SUN Pharma Advanced Research, Mark C. Genovese Shareholder of: Gilead Sciences, Inc., Consultant of: AbbVie, Amgen, Beigene, Eli Lilly and Co., Genentech, Inc., Gilead Sciences, Inc., Sanofi Genzyme, RPharm, and SetPoint, Employee of: Gilead Sciences, Inc., Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Franziska Matzkies Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Beatrix Bartok Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Kun Chen Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Deyuan Jiang Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Iyabode Tiamiyu Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos BV, Employee of: Galapagos BV, Sander Strengholt Shareholder of: Galapagos BV, Employee of: Galapagos BV, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Eli Lilly and Co., Galapagos, Gilead Sciences, Inc., and Pfizer, Consultant of: AbbVie, Eli Lilly and Co., Galapagos, Gilead Sciences, Inc., and Pfizer, Jacques-Eric Gottenberg Speakers bureau: AbbVie, Eli Lilly and Co., Galapagos BV, Gilead Sciences, Inc., Roche, Sanofi Genzyme, and UCB, Consultant of: Bristol Myers Squibb, Sanofi Genzyme, and UCB, Grant/research support from: Bristol Myers Squibb and Pfizer

Introduction Filgotinib (FIL), inhibiteur preferentiel de JAK1 per os, a ameliore les signes et les symptomes de la polyarthrite rhumatoide (PR) dans 3 essais de phase 3. [1] , [2] , [3] . Les patients (pts) PR ont une augmentation du risque de reactivation du zona vs la population generale. L’inhibition de JAK est associee a une incidence accrue des infections, y compris de zona [4] . Objectifs Evaluer la tolerance a long terme pour le zona dans l’ensemble du programme clinique du FIL. Patients et methodes Les pts dans l’analyse poolee des etudes DARWIN1–2, FINCH1–3 et des extensions DARWIN3 et FINCH4 ont ete inclus. L’ensemble des donnees controlees vs PBO incluait les pts recevant FIL100, FIL200 ou PBO jusqu’a S12 et l’ensemble controle par traitement actif comprenait les pts recevant FIL100, FIL200, adalimumab (ADA) ou methotrexate (MTX) jusqu’a S52. L’ensemble des donnees a long terme incluait les patients recevant FIL100 ou FIL200, ADA, MTX ou PBO dans les 7 etudes ; les donnees apres re-randomisation ont ete incluses et ont contribuees au traitement recu. Les taux d’incidence ajustes en fonction de l’exposition (TIAE) pour 100 patients-annees, jusqu’au dernier jour de suivi, et les IC95 % ont ete calcules a l’aide de la regression de Poisson. Un modele de regression logistique a ete utilise pour l’analyse des facteurs de risque de zona apparu sous traitement, et les risques relatifs (RR) (IC95 %) et les p valeurs ont ete fournis. Resultats Le Tableau 1 montre les TIAE de zona apparus sous traitement dans l’analyse poolee. Les taux de zona etaient inferieurs pour FIL200 vs PBO dans l’analyse controlee vs PBO de 12S. A S52, les taux de zona etaient plus eleves pour FIL200/100 vs controle par traitement actif. Les taux de zona a long terme sont plus eleves pour FIL200 vs FIL100. La Fig. 1 montre les facteurs de risque de zona apparu sous traitement selon un modele de regression logistique multivariee. Dans l’analyse a long terme, sur 104 pts avec un zona apparu sous traitement, 5 recevant FIL200 avaient des ATCD de zona ; le TIAE (IC95 %) etait de 8,7 (3,6–21,0). En Asie, dans l’analyse a long terme, les TIAE (IC95 %) de zona sous traitement etaient : 3,7 (1,7–8,1) pour FIL200, n = 197 ; 2,8 (1,3–6,3) pour FIL100, n = 158 ; 0 pour ADA, n = 40 ; 2,8 (0,4–19,6) pour MTX, n = 43 ; et 3,4 (0,5–23,8) pour PBO, n = 77. Dans l’analyse a long terme du reste du monde, les TIAE (IC95 %) etaient : 1,6 (1,2–2,1) pour FIL200, n = 2070 ; 0,9 (0,6–1,5) pour FIL100, n = 1489 ; 0,8 (0,2–3,1) pour ADA, n = 285 ; 0,9 (0,3–2,9) pour MTX, n = 373 ; et 0,7 (0,2–2,9) pour PBO, n = 704. La plupart des zona apparus sous traitement etait d’intensite legere a moderee et sans gravite ; 6 etaient graves ; 2 etaient des recidives. Aucun zona visceral n’est survenu au cours du programme ; il y a eu 1 zona genital, 1 zona dissemine et 1 zona ophtalmique. Le zona dissemine est survenu chez un pt avec un ATCD de zona. La lymphopenie n’etait pas associee au zona dans l’analyse controlee vs PBO de 12S. Conclusion Le zona etait plus frequent dans les 2 groupes FIL vs ADA ou MTX jusqu’a 52S mais comparable au PBO dans l’analyse controlee par PBO de 12S. Dans les analyses multivariees, les ATCD de zona, la region asiatique et l’âge ≥ 50 ans etaient associes a un risque accru de zona.

Aims SELECTION (NCT02914522) Maintenance evaluated filgotinib (FIL), a preferential JAK1 inhibitor, as maintenance therapy for patients (pts) with moderately to severely active ulcerative colitis (UC) who achieved clinical remission or Mayo Clinic Score (MCS) response after 10 weeks of FIL 200mg QD, FIL 100mg QD or placebo (PBO) induction. Methods Pts randomized to FIL induction were rerandomized 2:1 to their induction FIL dose or PBO; pts randomized to PBO induction continued PBO maintenance. Steroid tapering was mandatory. The primary endpoint was clinical remission at Week 58. Key secondary endpoints and exploratory endpoints were assessed at Week 58. Results 664 pts were treated in the Maintenance Study (n=93, 270, and 301 from induction with PBO, FIL 100mg and FIL 200mg); efficacy analyses included only FIL induction pts. Baseline demographics and disease characteristics were generally balanced across treatment arms; 40% were biologic experienced. Significantly higher proportion of pts on FIL 200mg or FIL 100mg were in clinical remission vs PBO. Significantly higher proportions of pts achieved key secondary endpoints with FIL 200mg vs PBO. More pts on FIL 200 mg or FIL 100mg achieved an MCS response and endoscopic improvement vs PBO. Incidences of adverse events (AEs), serious AEs and discontinuations due to AEs were similar across arms. Serious infection ( Conclusions FIL 200mg and FIL 100mg were effective as maintenance treatment for pts with moderately to severely active UC who had achieved clinical response to FIL induction treatment. FIL 200 mg met all key secondary endpoints including endoscopic, histologic and 6-month corticosteroid-free remission. FIL was well tolerated in pts with moderate to severely active UC. Funding Agencies None

The global prevalence of ulcerative colitis is increasing, and induction and maintenance of remission is a crucial therapeutic goal. We assessed the efficacy and safety of filgotinib, a once-daily, oral Janus kinase 1 preferential inhibitor, for treatment of ulcerative colitis.This phase 2b/3, double-blind, randomised, placebo-controlled trial including two induction studies and one maintenance study was done in 341 study centres in 40 countries. Eligible patients were aged 18-75 years with moderately to severely active ulcerative colitis for at least 6 months before enrolment (induction study A: inadequate clinical response, loss of response to or intolerance to corticosteroids or immunosuppressants, naive to tumour necrosis factor [TNF] antagonists and vedolizumab [biologic-naive]; induction study B: inadequate clinical response, loss of response to or intolerance to any TNF antagonist or vedolizumab, no TNF antagonist or vedolizumab use within 8 weeks before screening [biologic-experienced]). Patients were randomly assigned 2:2:1 to receive oral filgotinib 200 mg, filgotinib 100 mg, or placebo once per day for 11 weeks. Patients who had either clinical remission or a Mayo Clinic Score response at week 10 in either induction study entered the maintenance study. Patients who received induction filgotinib were rerandomised 2:1 to continue their induction filgotinib regimen or to placebo. Patients who received induction placebo continued receiving placebo. The primary endpoint was clinical remission by Mayo endoscopic, rectal bleeding, and stool frequency subscores at weeks 10 and 58. For the induction studies, efficacy was assessed in all randomised patients who received at least one dose of study drug or placebo within that study. For the maintenance study, efficacy was assessed in all patients randomised to any filgotinib treatment group in the induction studies who received at least one dose of study drug or placebo in the maintenance study. Patients who received placebo throughout the induction and maintenance study were not included in the full analysis set for the maintenance study. Safety was assessed in all patients who received at least one dose of the study drug or placebo within each study. This trial is registered with ClinicalTrials.gov, NCT02914522.Between Nov 14, 2016, and March 31, 2020, we screened 2040 patients for eligibility. 659 patients enrolled in induction study A were randomly assigned to receive filgotinib 100 mg (n=277), filgotinib 200 mg (n=245), or placebo (n=137). 689 patients enrolled into induction study B were randomly assigned to receive filgotinib 100 mg (n=285), filgotinib 200 mg (n=262), or placebo (n=142). 34 patients in induction study A and 54 patients in induction study B discontinued the study drug before week 10. After efficacy assessment at week 10, 664 patients entered the maintenance study (391 from induction study A, 273 from induction study B). 93 patients continued to receive placebo. 270 patients who had received filgotinib 100 mg in the induction study were randomly assigned to receive filgotinib 100 mg (n=179) or placebo (n=91). 301 patients who had received filgotinib 200 mg in the induction study were randomly assigned to receive filgotinib 200 mg (n=202) or placebo (n=99). 263 patients discontinued treatment in the maintenance study. At week 10, a greater proportion of patients given filgotinib 200 mg had clinical remission than those given placebo (induction study A 26·1% vs 15·3%, difference 10·8%; 95% CI 2·1-19·5, p=0·0157; induction study B 11·5% vs 4·2%, 7·2%; 1·6-12·8, p=0·0103). At week 58, 37·2% of patients given filgotinib 200 mg had clinical remission versus 11·2% in the respective placebo group (difference 26·0%, 95% CI 16·0-35·9; p0·0001). Clinical remission was not significantly different between filgotinib 100 mg and placebo at week 10, but was significant by week 58 (23·8% vs 13·5%, 10·4%; 0·0-20·7, p=0·0420). The incidence of serious adverse events and adverse events of interest was similar between treatment groups. In the induction studies, serious adverse events occurred in 28 (5·0%) of 562 patients given filgotinib 100 mg, 22 (4·3%) of 507 patients given filgotinib 200 mg, and 13 (4·7%) of 279 patients given placebo. In the maintenance study, serious adverse events were reported in eight (4·5%) of 179 patients given filgotinib 100 mg, seven (7·7%) of 91 patients in the respective placebo group, nine (4·5%) of 202 patients in the filgotinib 200 mg group, and no patients in the respective placebo group. No deaths were reported during either induction study. Two patients died during the maintenance study; neither was related to treatment.Filgotinib 200 mg was well tolerated, and efficacious in inducing and maintaining clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis.Gilead Sciences.

Background Filgotinib (FIL) is an orally administered, selective janus kinase 1 (JAK1) inhibitor in development for psoriatic arthritis (PsA). Efficacy and safety of FIL in patients with active PsA were evaluated in a 16-week phase 2 study (EQUATOR, NCT03101670). After 16 weeks, patients could roll-over to an Open Label Extension (OLE) Study (EQUATOR2, NCT03320876) for the purpose of evaluating long-term safety and efficacy. The aim of this analysis was to assess safety and efficacy through 52 weeks of exposure to filgotinib. Methods Patients who completed the randomised, double-blind, placebo-controlled study were eligible for participation in the OLE, during which all patients received once daily (qd) open-label FIL 200mg. In this interim analysis of OLE, for the safety analysis, all data were included from the screening in the core study up to the data cut of 18 April 2019 in the OLE. For the efficacy analysis, all data until OLE Week 52 visit for each patient were included (observed case analysis). Results Of the 131 patients randomised and dosed in EQUATOR, 124 (95%) completed the study and 122 (93%) enrolled in EQUATOR2; 50% were female and mean age was 50. At this interim analysis, 106/122 (87%) remained in the OLE (premature discontinuations during OLE due to: 4 for safety, 11 withdrew consent, and 1 for other reasons). Cumulative patient years of exposure (PYE) on FIL were 160, median time on FIL was 66 weeks. Key safety data are summarised in Table 1. Key ≥Grade 2 treatment-emergent laboratory abnormalities seen with FIL arm (N = 128) compared with PBO (N = 66) were lymphocyte decrease 11.1% vs 4.5%, neutrophil decrease 5.5% vs 0%, ALT increase 1.6% vs 1.5% and creatinine increase 0.8% vs 0%, respectively. At week 52, 34% of the patients fulfilled criteria for minimal disease activity and 81%, 55%, and 33% of patients, respectively, achieved ACR20/50/70 responses. Conclusion FIL 200mg qd was generally well tolerated and the safety profile in PsA was comparable to that observed in the FIL rheumatoid arthritis studies. The data from this interim analysis suggest that further improvement of the patient condition can be expected beyond 16 weeks of treatment. Disclosures L. Coates: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Lilly, Novartis, Pfizer, Prothena, Sun pharma, and UCB. P. Mease: Other; Received support from Abbvie, Amgen, BMS, Celgene, Galapagos, Genentech, Gilead, Janssen, Eli Lilly, Merck, Novartis, Pfizer, SUN, and UCB. D. Gladman: Other; Received support from Abbvie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB, BMS, and Galapagos. F. Van den Bosch: Other; Received support from Abbvie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, and UCB. A. Rychlewska-Hanczewska: Other; Received support from Galapagos and Gilead Sciences. C. Tasset: Corporate appointments; Employee of Galapagos NV. L. Meuleners: Corporate appointments; Employee of Galapagos NV. M. Trivedi: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Employee of Gilead Sciences, Inc... Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. R. Besuyen: Other; Employee of Galapagos NV. P. Helliwell: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Novartis, Pfizer, and UCB.

Background Anaemia, thrombocytopenia and leukopenia in rheumatoid arthritis (RA) patients treated with non-Janus Kinase 1 (JAK1) selective inhibitors may be due to inhibition of haematopoietic growth factors signalling through JAK2. Therefore, we investigated anaemia, thrombocytopenia and leukopenia in patients with active RA with prior inadequate response/intolerance to biologic disease-modifying anti-rheumatic drugs (bDMARDs) treated with filgotinib (FIL), a selective JAK1 inhibitor (FINCH-2; NCT02873936). Methods In the randomised, double-blind, placebo-controlled Phase 3 FINCH-2 trial, patients were randomised 1:1:1 to oral FIL 200 mg, 100 mg, or placebo (PBO) once daily plus conventional synthetic DMARDs for 24 weeks. In this subgroup analysis, we assessed shifts from baseline (BL) in haemoglobin (hgb), platelets (plt), neutrophils and lymphocytes. Results A total of 448 patients were treated; FIL 200 mg, n = 147; FIL 100 mg, n = 153; PBO, n = 148. Hgb, plt, lymphocyte and neutrophil counts remained consistent throughout the study. At BL, 28.8%, 0.9%, 2.2% and 5.8% patients had mild–moderate low hgb, plt, neutrophil and lymphocyte, respectively, and 1.1% had severely low lymphocyte levels. Of patients with mild–moderate hgb levels at BL, 13.1% with FIL 200 mg, 9.5% FIL 100 mg, and 7.6% PBO achieved normal hgb at Week 24, respectively (Table). Of those with normal BL hgb, only 6–9.8% had mild low levels at Week 24. Patients with BL mild-moderate low plts and neutrophils had normal levels at Week 24, except one with mild neutropenia on FIL 100 mg. Of patients with normal plt and neutrophil levels at BL, >94% maintained these at Week 24 in all treatment groups. By Week 24, 3.2%, 5.2% and 2.2% of patients treated with FIL 200 mg, FIL 100 mg and PBO, respectively, in the mild–moderate subgroup and 1.7% in the severe subgroup treated with FIL 100 mg had normal lymphocyte counts. Conclusion In this subgroup analysis, most patients with normal hgb, plt, lymphocyte and neutrophil at BL maintained them over 24 weeks of FIL treatment. Of the patients with mild–moderately low hgb at BL, >9% shifted towards normalisation. Similar patterns of improvement were observed for plt, lymphocyte and neutrophil counts. These results suggest that FIL does not increase the incidence of anaemia, thrombocytopenia or leukopenia in patients who entered the study with active RA despite prior bDMARDs.

Background:The Janus kinase-1 preferential inhibitor filgotinib (FIL) improved signs and symptoms of rheumatoid arthritis (RA) across the FIL clinical program.1–3Objectives:To assess FIL efficacy across geographic regions.Methods:Pooled data from patients (pts) meeting 2010 ACR/EULAR RA criteria randomised to once-daily FIL 200 mg (FIL200), FIL100 mg (FIL100), or placebo (PBO) with background conventional synthetic disease-modifying antirheumatic drugs in DARWIN 1 (P2; up to week [W]12) and FINCH 1–2 (P3; up to W24) studies were evaluated. Data were analysed by region: North America, South and Central America, Western Europe, Eastern Europe, Asia, South East (SE) Asia, and Other. W12 American College of Rheumatology 20% improvement (ACR20) and W24 Disease Activity Score in 28 joints (C-reactive protein) (DAS28[CRP]) Results:Despite high PBO response rates in Eastern Europe and South and Central America, greater proportions of pts receiving FIL200 or FIL100 vs PBO achieved ACR20 at W12 (P P Table 1.Proportion of pts achieving ACR20 and LSM change from baseline HAQ-DI at week 1ACR20HAQ-DIFIL200FIL100FIL200FIL100FIL200FIL100North America64.8*58.3*33.8−0.63*−0.58*−0.34n = 455(56.7, 72.9)(50.3, 66.4)(26.0, 41.6)(−0.70, −0.56)(−0.65, −0.51)(−0.41, −0.27)South and Central America77.277.357.4−0.77*−0.67*−0.43n = 283(68.1, 86.3)†(65.8, 86.2)†(46.9, 68.0)(−0.85, −0.68)(−0.75, −0.59)(−0.52, −0.35)Western Europe69.4*68.3*24.4−0.69*−0.61*−0.28n = 135(55.5, 83.3)(52.8, 83.8)(10.8. 38.1)(−0.80, −0.58)(−0.73, −0.49)(−0.40, −0.17)Eastern Europe77.1*69.1*54.6−0.62*−0.51*−0.34n = 822(71.9, 82.3)(63.5, 74.7)(48.5, 60.7)(−0.68, −0.56)(−0.57, −0.45)(−0.40, −0.28)Asia81.0*60.0†37.7−0.83*−0.61†−0.42n = 236(71.7, 90.3)(48.6, 71.4)(26.2, 49.1)(−0.92, −0.73)(−0.70, −0.52)(−0.52, −0.33)South East Asia70.2†71.1†39.5−0.61−0.57−0.45n = 135(56.1, 84.4)(56.8, 85.5)(23.8, 55.3)(−0.73, −0.49)(−0.69, −0.45)(−0.58, −0.33)Other60.052.439.1−0.56‡−0.60‡−0.33n = 69(38.8, 81.2)(28.6, 76.1)(17.0, 61.2)(−0.72, −41)(−0.76, −0.43)(−0.49, −0.17)Overall73.4*66.4*45.3−0.71*−0.61*−0.40N = 2135(70.1, 76.8)(62.9, 70.0)(41.5, 49.0)(−0.76, −0.66)(−0.66, −0.56)(−0.45, −0.35)Includes only patients initially randomised to the treatment groups in each study for the comparison of interest. ACR20 presented as percentage (95% CI); 95% CI was based on normal approximation method with a continuity correction; P values calculated from the logistic regression.HAQ-DI presented as LSM (95% CI); LSM, 95% CI, and P value calculated from a mixed-effects model for repeated measures.*P ACR20, American College of Rheumatology 20% improvement; CI, confidence interval; FIL, filgotinib; HAQ-DI, Health Assessment Questionnaire-Disability Index; LSM, least square mean; PBO, placebo.At W24, DAS28(CRP) P Conclusion:In exploratory analyses, ACR20, DAS28(CRP) References:[1]Genovese et al. JAMA. 2019;322:315–25.[2]Westhovens et al. Ann Rheum Dis. 2021; online first.[3]Combe et al. Ann Rheum Dis. 2021; online first.Disclosure of Interests:Maya H Buch Speakers bureau: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB, Consultant of: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB., Grant/research support from: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB., Tsukasa Matsubara Speakers bureau: Pfizer Japan, Nichi-Iko, Astellas, Meiji Seika, Bristol-Myers Squibb, AbbVie GK, Janssen, Chugai, Eisai, AYUMI, Bernard Combe Speakers bureau: BMS; Eli Lilly & Co.; Gilead Sciences, Inc.; MSD; Pfizer; Roche-Chugai; and UCB, Consultant of: AbbVie; Eli Lilly & Co.; Gilead Sciences, Inc.; Janssen; Pfizer; Roche-Chugai; and Sanofi, Grant/research support from: Novartis, Pfizer, and Roche-Chugai, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., YingMeei Tan Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Zhaoyu Yin Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Jaehyung Hong Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos, BV, Employee of: Galapagos, BV, Antonio Gomez-Centeno Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly & Co., Gebro, Janssen, Menarini, Merck Sharp & Dohme, Pfizer, Roche, Rubio, Sanofi, and UCB, Consultant of: AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Eli Lilly & Co., Gebro, Gilead Sciences, Inc., Hospira, Merck Sharp & Dohme, Pfizer, Roche, Rubio, Sandoz, Sanofi, Grant/research support from: Boehringer Ingelheim, Celltrion, Eli Lilly & Co., Galapagos NV, Gilead Sciences, Inc., Novartis, Pfizer, Roche, Sanofi, UCB, YL Biologics

Background:The Janus kinase (JAK)-1 preferential inhibitor filgotinib (FIL) improved rheumatoid arthritis (RA) signs and symptoms in 3 phase (P)3 trials.1–3 Like other RA therapies, JAK inhibition is associated with increased infection rates.4Objectives:To assess long-term safety across the FIL program regarding infections, including serious infections (SI).Methods:Patients (pts) meeting 2010 ACR/EULAR RA criteria in pooled analysis of P2 DARWIN 1–2 (D1–2), P3 FINCH 1–3 (F1–3), and long-term extension studies (DARWIN 3, FINCH 4) were included. The placebo (PBO)-controlled as-randomised data set included pts receiving FIL 100 mg (FIL100), FIL 200 mg (FIL200), or PBO up to week (W)12 (D1–2, F1–2). The active-controlled as-randomised data set included pts receiving FIL100, FIL200, adalimumab (ADA), or methotrexate (MTX) up to W52 (F1, F3). The long-term as-treated data set included pts in all 7 studies receiving FIL100 or FIL200; data after rerandomisation were included and contributed to treatment received.Exposure-adjusted incidence rates (EAIRs) per 100 patient-years exposure (PYE) and differences with 95% confidence intervals (CIs) were calculated using Poisson regression; EAIRs for tuberculosis (TB) in active controlled sets were calculated using an Exact Poisson method. Kaplan-Meier (KM) event probabilities with 95% CIs were provided for SI. If pts had multiple events within the same treatment period, only the first event was counted in EAIR calculation; PYE were calculated up to the last follow-up time or day before next treatment, including after first event. For KM analysis, time to event was calculated until the first event.Results:Of 2267/1647 pts in as-treated set receiving FIL200/FIL100, 1697 had treatment-emergent infection; 118 were SI. Baseline potential risk factors for pts with SI are in Table.Table 1.Baseline characteristics of pts with/without treatment emergent SIaParameter, n (%)SIN = 92No SIN = 2491Medical history Chronic lung disease13 (14.1)125 (5.0) Chronic renal disease3 (3.3)23 (0.9) Infections and infestations29 (31.5)499 (20.0)Baseline body mass index, kg/m2 64 (69.6)1749 (70.2) ≥3028 (30.4)742 (29.8)Age, years 67 (72.8)2006 (80.5) ≥6525 (27.2)485 (19.5)Former/current smoker30 (32.6)677 (27.2)Oral corticosteroids, mg 28 (56.0)731 (66.1) ≥7.522 (44.0)375 (33.9) Missing data421385aPhase 3 (FINCH 1-4) studies, as randomised.SI, serious infection.In 12W PBO-controlled period, infection rates were 17.9%/15.6%/13.3% for FIL200/FIL100/PBO. In 52W ADA-controlled period, infection EAIRs (95% CIs)/100 PYE were 46.9 (40.9, 53.7)/43.7 (38.0, 50.4)/43.4 (36.5, 51.5), FIL200/FIL100/ADA; and 38.5 (33.8, 43.9)/39.0 (31.1, 48.8)/42.2 (36.1, 49.3), FIL200/FIL100/MTX in 52W MTX-controlled period; 24.8 (23.1, 26.5)/34.4 (30.4, 38.8), FIL200/FIL100 in long-term analysis. In 12W PBO-controlled period, there was no active TB for FIL200/FIL100/PBO. In 52W ADA-controlled period, active TB EAIRs (95% CIs)/100 PYE were: 0 (0.0, 0.8)/0 (0.0, 0.8)/0.3 (0.0, 1.9), FIL200/FIL100/ADA and 0 (0.0, 0.6)/0 (0.0, 1.9)/0 (0.0, 1.0), FIL200/FIL100/MTX in 52W MTX-controlled period; 0/0.1 (0.0, 0.5), FIL200/FIL100 in long-term analysis.SI rate or EAIRs are in Figure. Most common infections were upper respiratory tract infection and nasopharyngitis; majority were low grade. Pneumonia was most common SI (Conclusion:EAIRs of infections and SI for FIL were similar to PBO, ADA, and MTX. At 52W, incidence rates of SI were comparable for FIL100 and FIL200. Long-term SI EAIR for FIL100 was slightly higher than for FIL200.References:[1]Genovese et al. JAMA. 2019;322:315–25.[2]Westhovens et al. Ann Rheum Dis. 2021; online first.[3]Combe et al. Ann Rheum Dis. 2021; online first.[4]Strand et al. Arthritis Res Ther. 2015;17:362.Disclosure of Interests:James Galloway Speakers bureau: Pfizer, Bristol-Myers Squibb, UCB and Celgene, Maya H Buch Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi, Grant/research support from: Pfizer, Roche, and UCB, Kunihiro Yamaoka Speakers bureau: AbbVie, Actelion Pharmaceuticals Japan, Asahikasei Pharma Corp, Astellas Pharma, AYUMI Pharma Co, Boehringer Ingelheim Japan, Bristol-Myers Squibb, Chugai Pharma, Daiichi Sankyo, Eisai Pharma, Eli Lilly, GlaxoSmithKline, Gilead G.K., Hisamitsu Pharma Co., Janssen Pharma, Mitsubishi-Tanabe Pharma, MSD, Nippon Kayaku, Nippon Shinyaku, Ono Pharma, Otsuka Pharma, Pfizer, Sanofi, and Takeda Industrial Pharma, Consultant of: Asahikasei Pharma Corp., AbbVie, Gilead G.K., Pfizer, Astellas Pharma Inc, Eli Lilly Japan K.K., and Japan Tobacco Inc., Grant/research support from: Takeda Industrial Pharma, Pfizer, Astellas Pharma, Daiichi Sankyo, Eli Lilly, Eisai Pharma, Teijin Pharma, MSD, Shionogi, Chugai Pharma, Nippon Kayaku, Mitsubishi-Tanabe Pharma, and AbbVie, Cianna Leatherwood Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Iyabode Tiamiyu Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Deyuan Jiang Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Lei Ye Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos BV, Employee of: Galapagos BV, Daniel Aletaha Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Grant/research support from: AbbVie, Novartis, Roche, Kevin Winthrop Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly and Co., Galapagos NV, Gilead Sciences, GlaxoSmithKline, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, and Pfizer

Background:The oral Janus kinase 1 preferential inhibitor filgotinib (FIL) significantly improved Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) inflammation scores (bone marrow oedema) in the spine and sacroiliac joints vs placebo (PBO) in the Phase 2 TORTUGA trial (NCT03117270) in patients with active ankylosing spondylitis (AS).1Objectives:This post-hoc analysis evaluated the effects of FIL on Canada-Denmark (CANDEN) MRI measures of spinal inflammation and structural lesions in patients from the TORTUGA trial.Methods:TORTUGA was a PBO-controlled, multicentre, double-blind, randomised trial. Patients with active AS (as per modified New York classification criteria, with sacroiliitis confirmed by central reading) were treated with FIL 200 mg (n=58) or PBO (n=58) once daily for 12 weeks. MRI of the total spine was conducted at baseline and at treatment end. Scans were re-evaluated post-hoc by 2 independent experts (blinded to time point and assigned treatment) using the CANDEN method;2 inter-reader discrepancies were resolved by an independent adjudicator. Observed changes from baseline were evaluated using analysis of covariance, with factors for treatment, baseline value, and randomisation stratification by prior tumour necrosis factor inhibitor use. Least-squares (LS) mean changes from baseline and between-group differences with 95% confidence intervals (CI) were calculated; P values are nominal.Results:MRI scans from 88 patients (47 FIL, 41 PBO) with an evaluable scan at baseline and Week 12 (or early termination) were re-evaluated. Baseline characteristics were generally similar between patients with/without an MRI scan. Of those with MRI scans, mean total spine inflammation score (which ranges from 0–614) was higher, and mean ankylosis score (which ranges from 0–460) was lower, in the FIL vs PBO group at baseline. Total spine inflammation scores decreased from baseline with FIL but not with PBO (Figure and Table; P=0.0003 for between-group difference). Cumulative probability plots favoured FIL over PBO for change from baseline in subregion inflammation scores, including posterolateral elements (i.e. sum of lesions in ribs, transverse processes, spinous processes, soft tissue inflammation, and postero-lateral vertebral body), facet joint, and vertebral body. Total spine fat lesion scores numerically increased from baseline in the FIL but not PBO group (P=0.0878 for between-group difference; Table). There were no significant differences between groups for changes in erosion (P=0.1956) or ankylosis (P=0.3888) scores (Table).Table 1.Change from baseline at Week 12 in CANDEN total spine inflammation, total spine fat, total spine bone erosion, and ankylosis scoresTreatment groupnSample mean (SE)LS mean (SE)95% CI of treatment meanLS mean of group difference (SE)95% CI of group differenceBetween-group P valueTotal spine inflammation scoreFilgotinib47–4.98 (0.96)–4.40 (1.13)–6.65, –2.15–4.49 (1.21)–6.85, –2.120.0003Placebo410.29 (0.78)0.09 (1.13)–2.17, 2.34Total spine fat scoreFilgotinib471.01 (0.62)1.09 (0.66)–0.22, 2.401.18 (0.69)–0.18, 2.550.0878Placebo41–0.25 (0.19)–0.09 (0.66)–1.40, 1.21Total spine bone erosion scoreFilgotinib470.01 (0.02)0.07 (0.03)0.00, 0.140.05 (0.04)–0.02, 0.120.1956Placebo41–0.02 (0.03)0.02 (0.03)–0.04, 0.09Total ankylosis scoreFilgotinib470.30 (0.29)0.23 (0.31)–0.40, 0.850.28 (0.34)–0.37, 0.940.3888Placebo41–0.01 (0.08)–0.06 (0.31)–0.68, 0.56SE, standard errorConclusion:This is the first PBO-controlled trial to demonstrate a decrease in inflammatory activity with FIL, not only in the spinal vertebrae but also in the postero-lateral elements of the spine and facet joints. As expected in a 12-week study period, no changes in erosion or ankylosis were seen, while fat lesions showed a tendency to increase with FIL. Larger trials are needed to confirm these results.References:[1]van der Heijde D, et al. Lancet 2018;392:2378–87.[2]Krabbe S, et al. RMD Open 2019;5:e001057.Acknowledgements:The TORTUGA trial was sponsored by Galapagos NV (Mechelen, Belgium) and co-funded by Galapagos NV and Gilead Sciences, Inc. (Foster City, CA, USA). Medical writing support was provided by Debbie Sherwood BSc, CMPP (Aspire Scientific Ltd, Bollington, UK), and funded by Galapagos NV.Disclosure of Interests:Xenofon Baraliakos Consultant of: AbbVie, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Hexal, Janssen, MSD, Novartis, Pfizer, Sandoz and UCB, Grant/research support from: AbbVie, Celgene, Novartis and UCB, Mikkel Østergaard Speakers bureau: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Orion, Pfizer, Roche, Sandoz, Sanofi and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Merck and Novartis, Robert B.M. Landewé Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Janssen (formerly Centocor), Merck, Pfizer, Roche, Schering and UCB, Consultant of: AbbVie, Ablynx, Amgen, AstraZeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, Roche, Schering, TiGenix and UCB, Grant/research support from: AbbVie, Amgen, Janssen (formerly Centocor), Novartis, Pfizer, Roche, Schering and UCB, Employee of: Director of Rheumatology Consultancy BV, William Barchuk Shareholder of: Gilead Sciences, Inc., Employee of: Currently employee of Gilead Sciences, Inc.; and former employee of AbbVie, Eli Lilly and Johnson & Johnson, Ke Liu Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Chantal Tasset Shareholder of: Galapagos, Employee of: Galapagos, Leen Gilles Employee of: Galapagos, Thijs Hendrikx Shareholder of: Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Walter P Maksymowych Speakers bureau: AbbVie, Janssen, Novartis, Pfizer and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Novartis, Pfizer and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited

Premenopausal bone loss increases fracture risk later in life. Depending on peak values, varying degrees of bone mass and microarchitectural loss can be tolerated. We suggest that risk-benefit assessments of drugs that cause premenopausal bone loss be individualized considering baseline status and subsequent BMD and TBS loss. It is logical that drug-induced loss of bone mass and microarchitecture in young adults increase fracture risk later in life. However, no existing data quantify how drug-induced bone loss in younger adults impacts fracture risk later in life. As such, no guidance exists to address the question “How much, if any, drug-induced bone loss in premenopausal women is acceptable?” Thus, we performed a systematic fracture risk modeling exercise examining various degrees of bone loss, and estimated the impact on 10-year major osteoporosis-related fracture risk later in life. The FRAX® tool was used in conjunction with BMD and trabecular bone score (TBS) adjustment to estimate major osteoporotic fracture probability later in life resulting from varying degrees of hypothetical premenopausal drug-induced BMD and TBS loss. The resulting 10-year fracture probabilities were assessed against the US and the UK treatment guidance to determine the amount of premenopausal BMD and TBS loss that would result in a recommendation to initiate medical treatment to reduce fracture risk later in life that would not otherwise have been recommended in the absence of premenopausal bone loss. For women whose peak bone mass is between the 5th and 50th percentiles, varying degrees of BMD and TBS loss could be tolerated without reaching treatment thresholds. The degree of tolerable bone loss was primarily dependent on baseline bone status. Those whose peak BMD and TBS are in the 50th percentile or above could tolerate a 10% reduction in BMD and TBS without reaching treatment thresholds by age 75, whereas those in the 5th percentile would reach treatment thresholds by age 75 with no drug-induced reduction in BMD or TBS. Women in the 25th percentile could tolerate a 4% BMD loss and 2% TBS decline without reaching treatment thresholds by age 75. For clinicians and regulatory bodies to assess the consequence of drug-induced premenopausal bone loss, we propose an individualized approach considering both loss of BMD and TBS in concert with baseline bone status and the resultant effect on fracture risk in later life using the assumption that such losses are irreversible.

Introduction De nombreux patients (pts) atteints de polyarthrite rhumatoide (PR) presentent une reponse inadequate aux bDMARDs. L’objectif de cette analyse est de determiner si la prise prealable d’un bDMARD affecte l’efficacite du FIL, inhibiteur selectif per os de JAK1. Patients et methodes L’etude internationale de phase 3 FINCH2 (NCT02873936) a inclus 448 pts atteints de PR active prealablement traites par bDMARD 1. Les pts ont ete randomises 1:1:1 pour recevoir FIL 200 ou 100 mg ou un placebo (PBO), 1×/j pendant 24 semaines. Le pourcentage de pts atteignant une faible activite de la maladie (LDA) ou une remission, mesures par le CDAI et le DAS28-CRP, a ete evalue a S24. Les resultats ont ete stratifies selon le nombre et le type de bDMARD prealablement recus. Resultats Sur les 448 pts inclus dans l’etude, 106 (23,7 %) avaient deja pris ≥ 3 bDMARDs. A S24, plus de pts recevant FIL ont atteint une LDA vs PBO, quel que soit le nombre et le type de bDMARD prealable. Pour les patients du bras FIL 200 (vs PBO), un score DAS28-CRP ≤ 3,2 a ete atteint a S24 respectivement par 52 % vs 26 %, 50 % vs 22 % et 40 % vs 9 % des pts ayant prealablement recu 1, 2 ou ≥ 3 bDMARD, et par respectivement 49 % vs 21 % et 46 % vs 16 % des pts ayant prealablement recu un anti-TNF ou un anti-IL6. A S24, les taux de remission etaient superieurs dans les bras FIL vs PBO. Pour le bras FIL 200 (vs PBO), un score DAS28-CRP Fig. 1 ). Les effets indesirables apparus sous traitement dans les sous-groupes etaient concordants avec ceux observes dans la population totale. Conclusion FIL a permis d’atteindre des taux de LDA et de remission plus eleves vs PBO chez les pts ayant prealablement recu un anti-IL-6 ou un anti-TNF ou 1, 2 ou ≥ 3 bDMARD, avec un profil de tolerance similaire a celui observe dans la population globale. La superiorite du FIL vs PBO chez des patients en echec de bDMARDs montre l’interet de l’inhibition selective de JAK1.

Introduction FIL, inhibiteur selectif de JAK1 par voie orale, associe au MTX, a montre dans l’etude FINCH1 une amelioration significative des signes et symptomes de la PR chez les patients [pts] MTX-IR [1] . L’objectif de cette analyse est d’evaluer dans cette etude, a l’aide de questionnaires patients (PRO), l’evolution de la douleur (EVA), de la fatigue (FACIT), des fonctions physiques (HAQ-DI) et de la qualite de vie (SF-36), dimensions importantes de la prise en charge pour les patients [2] , [3] . Patients et methodes Dans l’etude FINCH 1 ( NCT02889796 ), les patients presentant une PR active MTX-IR ont recu par voie orale FIL 200 mg + MTX (475 pts), FIL 100 mg + MTX (480 pts), placebo (PBO) + MTX (475 pts) ou adalimumab sous-cutane (ADA) 40 mg + MTX (325 pts) pendant ≤ 52 semaines. A S24, les patients qui recevaient le PBO ont ete rerandomises selon un rapport 1/1 pour recevoir FIL 100 ou 200 mg. Resultats Sur les 1755 patients inclus, 80,7 % ont recu le medicament a l’etude jusqu’a S52. Des S2 et jusqu’a S24, les pts FIL 200 ou 100 mg (vs PBO) ont eu une amelioration significativement superieure (p Fig. 1 A, B). Pour l’HAQ-DI, une proportion significativement plus grande de pts a atteint des S2 une difference minimale cliniquement importante (MCID, baisse ≥ 0,22 points) dans les deux groupes FIL 200 mg (52,5 % ; p Conclusion Dans l’etude FINCH1 menee sur 52 semaines chez des patients PR MTX-IR, FIL a ameliore rapidement et durablement l’etat fonctionnel, la douleur, la qualite de vie liee a la sante et la fatigue, par rapport au PBO et, dans certains cas, versus ADA.

Background:Despite effective treatments, many patients (pts) with rheumatoid arthritis (RA) have inadequate responses to biologic DMARDs (bDMARD-IR), highlighting an unmet need. It is unclear whether prior bDMARD use affects efficacy of the oral, selective JAK-1 inhibitor filgotinib (FIL).Objectives:To explore clinical response to FIL in bDMARD-IR pts stratified by mode of action (MOA) and number of prior bDMARDs.Methods:The global, phase 3 FINCH-2 (NCT02873936) study treated 448 bDMARD-IR pts with active RA.1Pts were randomised 1:1:1 to once-daily FIL 200 mg, FIL 100 mg, or placebo (PBO) for 24 weeks. Efficacy was assessed by percent of pts achieving low disease activity (LDA) or remission at week (W)24 as measured by CDAI and DAS28(CRP) stratified by number and MOA of prior bDMARDs. Comparisons were not adjusted for multiplicity. Nonresponder imputation was used.Results:In total, 448 bDMARD-IR pts were included, 105 with prior experience with ≥3 bDMARDs (Table). At W24, pts receiving FIL were in LDA at a higher proportion vs PBO, irrespective of number of prior bDMARDs or MOA (Figure 1). For pts receiving FIL 200 vs PBO, DAS28(CRP) ≤3.2 was achieved at W24 by 52% vs 26%, 51% vs 22%, and 38% vs 9% of pts with 1, 2, or ≥3 prior bDMARDs, respectively, and 49% vs 21% and 50% vs 13% of pts exposed to TNF or IL-6 inhibitors; for all subgroups, rates were significantly higher vs PBO (Figure 1). Delta between FIL 200 mg and PBO was maintained irrespective of number or type of prior bDMARDs. At W24, pts receiving FIL achieved remission at numerically higher rates vs PBO (Figure 2). For pts receiving FIL 200 mg vs PBO, DAS28(CRP) Table.Number and MOA of prior bDMARDsFIL 200 mgn = 147FIL 100 mgn = 153PBOn = 148TotalN = 448Prior bDMARDs 173 (49.7)86 (56.2)77 (52.0)236 (52.7) 237 (25.2)33 (21.6)36 (24.3)106 (23.7) ≥337 (25.2)34 (22.2)34 (23.0)105 (23.4)LOE ≥1 bDMARD125 (85.0)129 (84.3)126 (85.1)380 (84.8)Intolerance ≥1 bDMARD36 (24.5)34 (22.2)32 (21.6)102 (22.8)Prior TNFi121 (82.3)134 (87.6)124 (83.8)379 (84.6) LOE ≥1 TNFi97 (66.0)113 (73.9)103 (69.6)313 (69.9) Intolerance ≥1 TNFi25 (17.0)24 (15.7)24 (16.2)73 (16.3)Prior non-TNFi73 (49.7)62 (40.5)75 (50.7)210 (46.9) LOE ≥1 non-TNFi52 (35.4)43 (28.1)56 (37.8)151 (33.7) Intolerance ≥1 non-TNFi13 (8.8)13 (8.5)11 (7.4)37 (8.3)Prior IL-6i34 (23.1)35 (22.9)32 (21.6)101 (22.5) LOE ≥1 IL-6i25 (17.0)22 (14.4)21 (14.2)68 (15.2) Intolerance ≥1 IL-6i5 (3.4)10 (6.5)5 (3.4)20 (4.5)Data presented as n (%).i, inhibitor; LOE, lack of efficacy.Conclusion:Treatment with FIL vs PBO led to higher rates of LDA and remission in pts with IR to IL-6 or TNF inhibition, or to 1, 2, or ≥3 prior bDMARDs, with a similar safety profile to the overall study population. A significantly higher proportion of pts overall receiving FIL 200 mg vs PBO were in LDA at W24. Improved efficacy of FIL vs PBO in pts who previously failed multiple bDMARDs indicates distinct benefits of selective JAK-1 inhibition with FIL.References:[1]Genovese, et al.JAMA2019;322(4):315–25.Disclosure of Interests: :Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Grace C. Wright Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Exagen, Eli Lilly, Myriad Autoimmune, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, UCB, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Exagen, Eli Lilly, Myriad Autoimmune, Novartis, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, UCB, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd., Kenneth Kalunian Grant/research support from: Pfizer, Lupus Research Alliance, Sanford Consortium, Consultant of: Genentech, Nektar, BMS, Janssen, AstraZeneca, Biogen, Vielabio, Equillium, Eli Lilly, ILTOO, Abbvie, Amgen, Roche, Gilead, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Ying Guo Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Shangbang Rao Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., YingMeei Tan Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme

Background:EULAR guidelines recommend a treat-to-target approach focusing on reducing inflammation to prevent joint damage, physical disability, and mortality.1However, patients consider reduction in pain and fatigue, along with maintenance of physical function, and improvement in health-related quality of life (HRQoL) important areas for improvement with RA treatment.2In the FINCH 2 study, filgotinib (FIL)—a potent, selective, oral small molecule Janus kinase 1 inhibitor—in combination with conventional synthetic (cs)DMARD therapy significantly improved the signs and symptoms of rheumatoid arthritis (RA) in patients with an inadequate response to a biologic (b)DMARD compared with placebo (PBO).3In addition, patients experienced significant improvements in HAQ-DI at week (W)12 and W24 with FIL 100 mg (p 3Objectives:To evaluate the rate and magnitude of change in patient-reported outcomes (PROs) from FINCH 2 assessing pain, HRQoL, and fatigue.Methods:Patients in this double-blind, randomised study (NCT02873936) received FIL 200 mg, FIL 100 mg, or PBO while continuing csDMARD therapy. PROs were collected prospectively on day 1 and at the W2, W4, W8, W12, W14, W16, W20, and W24 visits for assessment of pain (VAS pain scale) and on day 1 and at W4, W12, and W24 for assessment of fatigue (FACIT-Fatigue) and HRQoL (SF-36). Changes from baseline for each PRO at each time point up to W24 were analysed longitudinally using a mixed-effects model for repeated measures. P values for the difference between each FIL arm and PBO at each time point were calculated.Results:Among the 448 patients randomised and treated (FIL 200 mg, n = 147; FIL 100 mg, n = 153; PBO, n = 148) 381 (85.0%) completed the study. Baseline mean (SD) VAS pain scale was 67 (21.0), SF-36 physical component summary (PCS) was 31.1 (7.89), SF-36 mental component summary (MCS) was 44.3 (11.6), and FACIT-Fatigue score was 24.4 (11.6); baseline values did not vary between treatment groups. Significantly greater improvements in VAS pain scores began at W2 and were maintained through W24 for patients who received either dose of FIL vs PBO (Fig 1A). FIL also significantly improved patients’ fatigue at W4, W12, and W24 compared with PBO for those receiving 200 mg doses, and at W4 and W12 for those receiving 100 mg doses (Fig 1B). HRQoL related to physical functioning (SF-36 PCS) was significantly enhanced at W4, W12, and W24 with both doses of FIL as compared with PBO (Fig 2A). Improvements to mental-health-related QoL (SF-36 MCS) were reported for FIL as early as W4 and maintained through W24, with statistically significant improvements at W4 and W12 for FIL 200 mg vs PBO (Fig 2B).Conclusion:In a patient population with refractory disease that had inadequate response to prior bDMARDs and had significant disease at baseline, FIL treatment—coadministered with csDMARD therapy—was able to provide rapid and sustained improvements in key measures of pain, HRQoL, and fatigue as reported by patients.References:[1]Smolen, et al.Ann Rheum Dis. 2017;76:960–77.[2]Fautrel, et al.Rheumatol Int.2018;38:935–47.[3]Genovese, et al.JAMA. 2019;322(4):315–25.Disclosure of Interests:David Walker Grant/research support from: Gilead, Consultant of: Gilead, Lilly, Pfizer, Roche, Speakers bureau: Lilly, Pfizer, Roche, Tsutomu Takeuchi Grant/research support from: AbbVie, Asahikasei Pharma Corp., Astellas Pharma, Inc., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Nipponkayaku Co. Ltd., Shionogi & Co., Ltd., Takeda Pharmaceutical Co., Ltd., UCB Japan, Consultant of: Astellas Pharma, Inc., Chugai Pharmaceutical Co, Ltd., Eli Lilly Japan,, Speakers bureau: Abbvie, AYUMI Pharmaceutical Corp., Bristol-Myers Squibb, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan, Gilead Sciences, Inc., Mitsubishi-Tanabe Pharma Corp., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd, Beatrix Bartok Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Shangbang Rao Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., I-Heng Lee Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme

Background:Filgotinib (FIL), an oral, potent, selective JAK-1 inhibitor, provided statistically significant and clinically meaningful improvement in rheumatoid arthritis (RA) signs and symptoms, physical function, radiographic progression, and quality of life in a comprehensive clinical program of 4 phase 3 (FINCH 1–4;NCT02889796,NCT02873936,NCT02886728,NCT03025308) and 3 phase 2 (DARWIN 1–3;NCT01668641,NCT01894516,NCT02065700) trials in patients (pts) with early and biologic-refractory RA.1–3Objectives:To assess long-term safety of FIL.Methods:Treatment-emergent adverse events (TEAEs) from the FIL clinical program were integrated and presented for pts receiving FIL 200 mg or FIL 100 mg QD (including pts who transitioned to FIL from placebo [PBO], methotrexate [MTX], adalimumab [ADA], or another dose of FIL) as well as pts receiving PBO, MTX, and ADA across all 7 studies. Exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY) were calculated for adverse events (AEs) of interest per treatment. Incidence was total number of pts with events, and PY exposure was time between first and last doses. Major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) were centrally adjudicated by an independent committee.Results:Across the 7 trials, 4057 pts with RA (2227 pts FIL 200 mg; 1600 pts FIL 100 mg) received >1 dose of treatment for 5493 total PY of exposure (3079.2 PY FIL 200 mg; 1465.3 PY FIL 100 mg) (Table). EAIRs of serious AEs and TEAEs leading to death in pts receiving FIL were comparable to those for PBO, ADA, or MTX, with no dose-dependent effect (Figure 1). EAIR for herpes zoster (HZ), serious, and opportunistic infections are shown in Figure 2. EAIR for HZ were low overall, but numerically slightly higher for FIL relative to PBO, ADA, and similar to MTX. Serious infection EAIRs were comparable between pts receiving FIL 100 mg and ADA, and numerically slightly lower for FIL 200 mg and MTX. Rates of opportunistic infections (including active tuberculosis) were low overall; EAIR for FIL doses were comparable to placebo and numerically lower than ADA or MTX. Rates of MACE and VTE were numerically lower for FIL relative to PBO (Figure 1). Malignancies, including nonmelanoma skin cancer, were rare overall, and rates were low in pts receiving FIL (Figure 1).Table.Total exposure to study treatments pooled from 7 studiesNumber of patientsPatient-years of exposureFIL 200 mg22273079.2FIL 100 mg16001465.3ADA325290.1MTX416356.2PBO781302.4Patients could contribute to >1 treatment group.ADA, adalimumab; FIL, filgotinib; MTX, methotrexate; PBO, placebo.Conclusion:In this integrated analysis, FIL was well-tolerated, and no new safety concerns were identified. No clinically meaningful dose-dependent safety effects were observed. MACE and VTE were uncommon. Serious infections rates were low; HZ reactivation was infrequent. Safety results were consistent with selective JAK-1 inhibition and highlight the favourable safety and tolerability of FIL in patients with RA.References:[1]Genovese, et al.JAMA2019;322(4):315–25.[2]Westhovens, et al.Ann Rheum Dis2017;76:998–1008.[3]Kavanaugh, et al.Ann Rheum Dis2017;76:1009–19.Disclosure of Interests:Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme, Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd., Alan Kivitz Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim,,Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, Franziska Matzkies Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Lei Ye Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Deyuan Jiang Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Ying Guo Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Beatrix Bartok Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB

ObjectiveTo examine the effects of filgotinib, an oral, selective Janus kinase 1 inhibitor, on health-related quality of life (HRQoL) using the Psoriatic Arthritis Impact of Disease (PsAID)9 questionnaire in active PsA.MethodsPatients were randomized 1 : 1 to filgotinib 200 mg or placebo once daily for 16 weeks in EQUATOR, a multicentre, double-blind, phase 2 randomized controlled trial. HRQoL was assessed with PsAID9 at Weeks 4 and 16. Change from baseline in total and individual domain scores, plus the proportions of patients achieving minimal clinically important improvement (MCII; ⩾3 points) and patient-accepted symptom status (PASS; score ResultsOne hundred and thirty-one patients were randomized to filgotinib or placebo. Filgotinib effects on PsAID9 were observed from Week 4. At Week 16, mean (s.d.) change from baseline in PsAID9 was –2.3 (1.8) and –0.8 (2.2) for filgotinib and placebo, respectively (least-squares mean of group difference –1.48 [95% CI –2.12, –0.84], P < 0.0001), with significant improvements in all domains vs placebo. Significantly more patients on filgotinib achieved MCII (group difference 25.4% [95% CI 8.92, 39.99], P = 0.0022) and PASS (group difference 29.6% [95% CI 10.65, 45.60], P = 0.0018) at Week 16 vs placebo. Similar improvements in SF-36 were observed, with moderate to strong negative correlation between PsAID9 and SF-36.ConclusionFilgotinib significantly improved HRQoL vs placebo in patients with active PsA, as measured by PsAID9. To our knowledge, EQUATOR is the first randomized controlled trial to evaluate PsAID9.Trial registrationClinicalTrials.gov, https://clinicaltrials.gov/ct2/show, NCT03101670.

Background: Filgotinib (FIL) is an oral, selective Janus kinase 1 inhibitor under clinical investigation in a number of inflammatory diseases. FIL significantly improved multiple disease domains vs placebo (PBO) in patients with active psoriatic arthritis (PsA) in the multicenter, double-blind, phase 2 EQUATOR trial (NCT03101670) [1]. Objectives: To evaluate the effect of FIL vs PBO on patient reported outcomes (PROs) in EQUATOR and the extent to which effects on composite disease endpoints translate to clinically relevant improvements for patients. Methods: Patients were randomized 1:1 to FIL 200 mg or PBO once daily for 16 weeks [1]. Patient’s Global Assessment of Disease Activity (PtGADA), pain intensity (visual analog scale), Pruritus Numerical Rating Scale (NRS), Health Assessment Questionnaire Disability Index (HAQ-DI), 36-Item Short Form Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS), and Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F) were assessed at week 16. Analysis of covariance was used to compare changes from baseline in outcomes between groups. Proportions of patients achieving normative PRO scores or minimal clinically important differences (MCIDs) were compared using Cochran-Mantel-Haenszel tests [2, 3]. Results: FIL significantly improved multiple PROs vs PBO at week 16 (Table). Proportions of patients reaching normative PRO values for FACIT-F and SF-36 PCS (=40 or 50, respectively), and achieving MCIDs in HAQ-DI and SF 36 PCS, were significantly greater for FIL vs PBO (Table). Significant improvement in 6/8 SF 36 domains was observed at week 16 with FIL vs PBO (Fig a). Improvement in most individual FACIT F items was also observed (Fig b). Conclusion: In EQUATOR, FIL-treated patients with active PsA reported greater and clinically meaningful improvements in most PROs at week 16 vs PBO, mirroring improvements previously reported with FIL in disease activity measures [1]. References [1] Mease P, et al. Lancet 2018;392:2367–77. [2] Mease P, et al. J Rheumatol 2011;38:2461–5. [3] Genovese M, et al. Arthritis Res Ther 2018;20:57. Acknowledgement: This study was funded by Galapagos NV (Mechelen, Belgium). Medical writing support was provided by Alice Wareham PhD, CMPP (Aspire Scientific Ltd, Bollington, UK) and funded by Galapagos NV. Disclosure of Interests: Laura C Coates Grant/research support from: AbbVie, Celgene, Lilly, Novartis and Pfizer, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead Sciences Inc., Janssen, Lilly, Novartis, Pfizer, Prothena Corp and UCB, Philip J Mease Grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: AbbVie, Amgen, BMS, Galapagos, Gilead Sciences, Inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer and UCB, Dafna D Gladman Grant/research support from: AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Filip van den Bosch Consultant for: AbbVie, BMS, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, BMS, Janssen, Lilly, Merck, Novartis, Pfizer and UCB., Chantal Tasset Shareholder of: Warrants from Galapagos, Employee of: Galapagos, Luc Meuleners Shareholder of: Warrants from Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Warrants from Galapagos, Employee of: Galapagos, Jingjing Gao Shareholder of: AbbVie and Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Mona Trivedi Shareholder of: Amgen and Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Thijs Hendrikx Shareholder of: Warrants from Galapagos, Employee of: Galapagos, Philip Helliwell Grant/research support from: Paid to charity: from AbbVie, Janssen and Novartis, Consultant for: Paid to charity: from AbbVie, Amgen, Pfizer, and UCB and Celgene. Paid to self: from Celgene and Galapagos

Background: Filgotinib (FIL) is an oral, selective Janus kinase 1 inhibitor that, compared with placebo (PBO), significantly improved patient-reported outcomes in active psoriatic arthritis (PsA) in the phase 2 EQUATOR randomized controlled trial (RCT; NCT03101670) [1]. PsA Impact of Disease (PsAID) is a validated, EULAR-developed, PsA-specific questionnaire for measurement of health–related quality of life (HRQoL) [2]. PsAID is less complex than generic HRQoL tools, such as the 36–Item Short Form Survey (SF–36). To our knowledge, this is the first RCT reporting efficacy results using PsAID9. Objectives: To determine the effect of FIL vs PBO on PsAID9 in participants of EQUATOR. Methods: EQUATOR was a multicenter, double-blind study in which patients were randomized 1:1 to FIL 200 mg or PBO once daily for 16 weeks [1]. HRQoL was assessed at weeks 4 and 16 with PsAID9 (total and individual domain scores [each scored 0–10]) and, for comparison, with the Physical Component Summary (PCS) and Mental Component Summary (MCS) of SF-36. Higher PsAID scores correspond to greater impact of PsA [2]. Analysis of covariance was used to compare outcomes between groups. Results: There were 131 participants in EQUATOR (FIL: n=65; PBO: n=66). Mean (standard deviation [SD]) age was 49 (12.2) and 50 (10.9) years and mean (SD) baseline PsAID9 scores were 5.8 (1.6) and 5.7 (2.0) for FIL and PBO, respectively. Effects of FIL on PsAID9 and SF-36 scores were observed as early as week 4. FIL significantly improved PsAID9 total scores vs PBO; at week 16, PsAID9 total scores were 3.5 (2.0) for FIL and 4.9 (2.2) for PBO. Mean change (SD) from baseline at week 16 was –2.3 (1.8) vs –0.8 (2.2), respectively (Figure 1a); least-squares (LS) mean of group difference (95% confidence interval) was –1.48 (–2.12, –0.84), p Conclusion: Compared with PBO, FIL significantly improved disease impact in patients with active PsA, as measured by the PsA-specific PsAID9 total score and individual domain scores. Significant improvement in SF-36 PCS score was also seen with FIL. Reference [1] Mease P, et al. Lancet 2018;392:2367–77. 2. Orbai AM, et al. J Rheumatol2018;doi: 10.3899/jrheum.181077. Acknowledgement: This study was funded by Galapagos NV (Mechelen, Belgium). Medical writing support was provided by Alice Wareham PhD, CMPP (Aspire Scientific Ltd, Bollington, UK) and funded by Galapagos NV. Disclosure of Interests: Ana-Maria Orbai Grant/research support from: AbbVie, Celgene, Horizon Pharma, Janssen, Lilly, and Novartis, Consultant for: Lilly, Janssen, Novartis, Pfizer, and UCB, Alexis Ogdie Grant/research support from: (To my university) Novartis, Pfizer, Grant/research support from: Novartis, Pfizer, Grant/research support from: Novartis, Pfizer, Grant/research support from: Novartis, Pfizer, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly and Company, Novartis, Pfizer, and Takeda, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Novartis, Pfizer Inc, Takeda, Consultant for: Abbvie, Amgen, BMS, Celgene, Corrona, Lilly, Novartis, Pfizer, Takeda, Consultant for: Abbvie, Amgen, BMS, Celgene, Corrona, Lilly, Novartis, Pfizer, Takeda, Laure Gossec Grant/research support from: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Sanofi, and UCB, Consultant for: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, MSD, Nordic Pharma, Novartis-Sandoz, Pfizer, Roche, Sanofi, and UCB, Consultant for: L Gossec has received honoraria from Celgene as investigator for this study, William Tillett Grant/research support from: AbbVie, Celgene, and Lilly, Consultant for: AbbVie, Celgene, Lilly, Novartis, and Pfizer, Speakers bureau: Abbvie, Celgene, Lilly, Janssen, Novartis, UCB, and Pfizer, Ying Ying Leung Grant/research support from: Abbvie, Novartis, Speakers bureau: Abbvie and Novartis, Speakers bureau: Novartis, Jingjing Gao Shareholder of: AbbVie and Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Mona Trivedi Shareholder of: Amgen and Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Chantal Tasset Shareholder of: Warrants from Galapagos, Employee of: Galapagos, Luc Meuleners Shareholder of: Warrants from Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Warrants from Galapagos, Employee of: Galapagos, Thijs Hendrikx Shareholder of: Warrants from Galapagos, Employee of: Galapagos, Laura C Coates Grant/research support from: AbbVie, Celgene, Lilly, Novartis and Pfizer, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead Sciences Inc., Janssen, Lilly, Novartis, Pfizer, Prothena Corp and UCB

Background Filgotinib (FIL) is an oral, selective Janus kinase 1 inhibitor in development for the treatment of several inflammatory diseases. In the phase 2 EQUATOR trial (NCT03101670), FIL was efficacious vs placebo (PBO) in patients with active psoriatic arthritis (PsA), and was well tolerated [1]. Objectives To evaluate the onset and maintenance of response to FIL vs PBO in EQUATOR by evaluating patient–level response over time. Methods EQUATOR was a 16-week, multicenter, double-blind study in which patients with active PsA were randomized 1:1 to FIL 200 mg or PBO once daily [1]. Disease activity was assessed at screening, day 1 and weeks 1, 2, 4, 8, 12 and 16, and the primary efficacy endpoint was the proportion of patients achieving 20% American College of Rheumatology (ACR20) response. The onset of response was assessed by calculating the median time to ACR20 response using the Kaplan-Meier method and compared between FIL and PBO using the log-rank test. Maintenance of response was assessed by analysing ACR20 response patterns over time in the FIL and PBO groups. Results Of 131 patients randomized (FIL: n=65; PBO: n=66), 124 (95%) completed the study. Demographics and baseline disease characteristics were similar between groups. The onset of response to FIL was early, with a median (95% confidence interval) time to first ACR20 response of 4.07 weeks (2.29, 4.14) in the FIL group compared with 12.29 weeks (12, not reached) in the PBO group (p Conclusion In general, patients treated with FIL achieved an ACR20 response earlier than those on PBO and these responses appeared to be more stable. In the PBO group, there were more occurrences of the response being lost over time and fewer cases of regaining a lost response. Reference [1] Mease P, et al. Lancet2018;392:2367–77. Acknowledgement This study was funded by Galapagos NV (Mechelen, Belgium). Medical writing support was provided by Alice Wareham PhD, CMPP (Aspire Scientific Ltd, Bollington, UK) and funded by Galapagos NV. Disclosure of Interests Philip J Mease Grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: AbbVie, Amgen, BMS, Galapagos, Gilead Sciences, Inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer and UCB, Dafna D Gladman Grant/research support from: AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Filip van den Bosch Consultant for: AbbVie, BMS, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, BMS, Janssen, Lilly, Merck, Novartis, Pfizer and UCB., Mykola Stanislavchuk Grant/research support from: AstraZeneca, Celltrion, Galapagos, Genentech, GlaxoSmithKline, Human Genome, Lilly, MedImmune, Pfizer, Roche and UCB, Anna Rychlewska-Hanczewska Grant/research support from: Galapagos and Gilead Sciences, Inc., Chantal Tasset Shareholder of: Warrants from Galapagos, Employee of: Galapagos, Luc Meuleners Shareholder of: Warrants from Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Warrants from Galapagos, Employee of: Galapagos, Jingjing Gao Shareholder of: AbbVie and Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Mona Trivedi Shareholder of: Amgen and Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Laura C Coates Grant/research support from: AbbVie, Celgene, Lilly, Novartis and Pfizer, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead Sciences Inc., Janssen, Lilly, Novartis, Pfizer, Prothena Corp and UCB, Philip Helliwell Grant/research support from: Paid to charity: from AbbVie, Janssen and Novartis, Consultant for: Paid to charity: from AbbVie, Amgen, Pfizer, and UCB and Celgene. Paid to self: from Celgene and Galapagos

Background:Filgotinib (FIL), a novel preferential Janus kinase 1 inhibitor, was assessed in patients with active psoriatic arthritis (PsA) in the 16-week, Phase 2, EQUATOR trial (NCT03101670).1 EQUATOR2 (NCT03320876) is the open-label extension (OLE). As previously reported, an interim analysis of the OLE showed that the majority of patients had clinical resolution of enthesitis by Week 52.2Objectives:This post-hoc analysis evaluated the effect of FIL on clinical enthesitis after 100 weeks of treatment in the OLE, as assessed using the Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index, and evaluated the discriminatory capacity of the two indices. In addition, we assessed which of the sites included in LEI and SPARCC were most frequently involved and whether treatment effect was consistent across sites.Methods:In EQUATOR, patients with active moderate-to-severe PsA (≥5 swollen joints and ≥5 tender joints, fulfilling Classification for PsA criteria) were randomised 1:1 to receive oral FIL 200 mg or placebo (PBO) once daily (QD) for 16 weeks. At Week 16, all patients could continue into the OLE, receiving FIL 200 mg QD for up to an additional 304 weeks. We compared changes from core baseline in LEI and SPARCC measures, the effect on enthesitis at sites included in LEI and SPARCC assessments and the discriminatory capacity of both enthesitis indices.Results:Of 131 patients randomised to EQUATOR, 122 entered the OLE. There was strong agreement between LEI and SPARCC at baseline. While most patients had enthesitis at baseline according to either index (76/131 [58.0%] by LEI; 85/131 [64.9%] by SPARCC), a minority had enthesitis at a large number of sites (6.9% with 5–6 LEI sites; 12.2% with ≥9 SPARCC sites). The sites most frequently involved at baseline were the lateral epicondyle humerus and Achilles tendon, sites common to both LEI and SPARCC. There was greater variability in the change from baseline to Week 16 in SPARCC compared with LEI (Table 1). LEI showed a greater discriminatory capacity than SPARCC when change from baseline was compared for FIL vs PBO at Week 16, as shown by higher absolute standardised mean difference: −0.70 (LEI) and −0.30 (SPARCC) (observed cases; Table 1). Subgroup analyses indicated that the treatment effect of FIL vs PBO at Week 16 for all sites was consistent with the overall treatment effect seen for LEI or SPARCC, and indicative of an improvement with FIL vs PBO for nearly all sites. The proportion of patients with enthesitis decreased from baseline up to OLE Week 100 (Figure 1). There were no major differences in long-term effect on enthesitis between sites.Conclusion:FIL improved enthesitis consistently across sites compared with PBO. Rapid improvement in enthesitis was seen up to Week 16 of the core study and improvements continued up to Week 52, after which responses were generally stable up to Week 100. LEI assesses fewer locations than SPARCC, but reassuringly captured the sites most commonly affected by enthesitis; LEI also had greater discriminatory capacity.References:[1]Mease P, et al. Lancet 2018;392:2367–77[2]Mease P, et al. Arthritis Rheumatol 2020;72(suppl 10): abstract 0910Figure 1.Acknowledgements:EQUATOR and EQUATOR2 were sponsored by Galapagos NV (Mechelen, Belgium) and co-funded by Galapagos NV and Gilead Sciences, Inc (Foster City, CA, USA). Eline Vetters, Leen Gilles, Benjamin Pett and his team, all employees of Galapagos, provided assistance with statistical analyses. Medical writing/editorial support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and funded by Galapagos NV.Disclosure of Interests:Philip Helliwell Speakers bureau: Janssen, Novartis, Paid instructor for: Pfizer, Consultant of: Eli Lilly, Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, and Pfizer, Filip van den Bosch Consultant of: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Merck and UCB, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Lien Gheyle Shareholder of: Galapagos, Employee of: Galapagos, Mona Trivedi Shareholder of: Gilead Sciences, Amgen, Employee of: Gilead Sciences, Muhsen Alani Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Franck Olivier Le Brun Shareholder of: Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer, SUN and UCB.

Background:The once daily, oral Janus kinase (JAK)-1 preferential inhibitor filgotinib (FIL) improved signs and symptoms of rheumatoid arthritis (RA) in phase (P)3 trials.1-3 Patients (pts) with RA have increased herpes zoster (HZ) reactivation risk vs the general population. JAK inhibition is associated with increased infection incidence, including HZ.4Objectives:To assess long-term safety of FIL across the global clinical program with respect to HZ.Methods:Pts meeting 2010 ACR/EULAR RA criteria in a pooled analysis of P2 DARWIN 1–2 (D1–2), P3 FINCH 1–3 (F1–3), and long-term extension studies (D3, F4) were included. Placebo (PBO)-controlled as-randomised analysis included pts receiving FIL 100 mg (FIL100), FIL 200 mg (FIL200), or PBO up to week (W)12 (D1–2, F1–2); active-controlled as-randomised analysis included pts receiving FIL100, FIL200, adalimumab (ADA), or methotrexate (MTX) up to W52 (F1, F3). Long-term as-treated analysis included pts in all 7 studies receiving FIL100, FIL200, ADA, MTX, or PBO; data after re-randomisation were included and contributed to treatment received. Exposure-adjusted incidence rates (EAIR)/100 patient-years, calculated up to the last follow-up time or day, and differences with 95% confidence intervals (CIs) were calculated from the Poisson model. Logistic regression model was used for treatment-emergent (TE) HZ risk factor analysis and odds ratio (95% CI) and P value were provided.Results:Table 1 shows TE HZ EAIRs in a pooled analysis. Rates of HZ were lower for FIL200 vs PBO during the 12W PBO-controlled period. At 52W, HZ rates were higher for FIL200/100 vs active control. Long-term HZ rates increased for FIL200 vs FIL100.Table 1.EAIR of treatment-emergent herpes zosterNPatient-years exposureEAIR(95% CI)EAIR diff(95% CI vs PBO/active control)12W PBO-controlled FIL200777179.80.6 (0.1, 3.9)−0.56 (−2.5, 1.3) FIL100788181.61.1 (0.3, 4.4)−0.02 (−2.2, 2.2) PBO781178.41.1 (0.3, 4.5)Active-controlled, as-randomiseda FIL200475439.71.4 (0.6, 3.0)0.69 (−0.7, 2.1) FIL100480443.40.9 (0.3, 2.4)0.23 (−1.1, 1.5) ADA325297.60.7 (0.2, 2.7)Active-controlled, as-randomiseda FIL200626578.01.7 (0.9, 3.2)0.65 (−0.8, 2.2) FIL100207195.01.5 (0.5, 4.8)0.46 (−1.6, 2.5) MTX416372.21.1 (0.4, 2.9)Long-term as-treatedb FIL20022674047.71.8 (1.4, 2.3)NC FIL10016472032.91.1 (0.8, 1.7)NCaup to W52. bdata cut for LTE FINCH 4, Sept 19, 2019; DARWIN 3, April 26 2019.ADA, adalimumab; CI, confidence interval; EAIR, exposure-adjusted incidence rate; FIL, filgotinib; MTX, methotrexate; NC, not calculated; PBO, placebo; W week.Figure 1 shows multivariate logistic regression model of TE risk factors.Of 104 pts with TE HZ in long-term as-treated analysis set, 5 receiving FIL200 had history of HZ; EAIR (95% CI) was 8.7 (3.6–21.0). Of 8 pts with multiple events, 3 had events of differing severity for the same HZ episode.EAIRs (95% CI) of TE HZ in Asia were: 3.7 (1.7–8.1) FIL200, n=197; 2.8 (1.3–6.3) FIL100, n=158; 0 ADA, n=40; 2.8 (0.4–19.6) MTX, n=43; and 3.4 (0.5–23.8) PBO, n=77 in long-term as-treated population. EAIRs (95% CI) in rest of the world were: 1.6 (1.2–2.1) FIL200, n=2070; 0.9 (0.6–1.5) FIL100, n=1489; 0.8 (0.2–3.1) ADA, n=285; 0.9 (0.3–2.9) MTX, n=373; and 0.7 (0.2–2.9) PBO, n=704 for all pts as-treated.Most TE HZ infections were mild to moderate and non-serious; 6 were serious; 2 were recurrences. No visceral TE HZ occurred across the FIL RA program; there was 1 case each of genital, disseminated, and ophthalmic HZ. The disseminated HZ occurred in a pt with prior HZ history. Lymphopenia was not associated with HZ during the PBO-controlled W12 period.Conclusion:HZ was more common in both FIL groups vs ADA or MTX up to 52 weeks but comparable vs PBO during the 12-week placebo-controlled period. In multivariate analyses, prior history of HZ, Asian region, and age ≥50 years were associated with increased HZ risk.References:[1]Genovese et al. JAMA. 2019;322:315–25.[2]Westhovens et al. Ann Rheum Dis. 2021; online first.[3]Combe et al. Ann Rheum Dis. 2021; online first.[4]Higarashi and Honda. Drugs. 2020;80:1183–201.Disclosure of Interests:Kevin Winthrop Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly and Co., Galapagos NV, Gilead Sciences, GlaxoSmithKline, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, and Pfizer, Maya H Buch Speakers bureau: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB, Consultant of: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB, Grant/research support from: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB, Jeffrey Curtis Grant/research support from: AbbVie, Amgen, BMS, Corrona, Eli Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, and UCB, Gerd Rüdiger Burmester Speakers bureau: AbbVie; Eli Lilly; Pfizer; and Gilead Sciences, Inc., Consultant of: AbbVie; Eli Lilly; Pfizer; and Gilead Sciences, Inc., Daniel Aletaha Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Medac, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, Sanofi/Genzyme, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, and Sanofi/Genzyme, Grant/research support from: AbbVie, Merck Sharp & Dohme, Novartis, and Roche, Koichi Amano Speakers bureau: AbbVie GK, Astellas, Chugai Pharmaceutical Co. Ltd., Eli Lilly, GlaxoSmithKline KK, Pfizer Japan, Mitsubishi-Tanabe Pharma, Grant/research support from: Asahi Kasei Pharma, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Iyabode Tiamiyu Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Cianna Leatherwood Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Lei Ye Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Qi Gong Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos, BV, Employee of: Galapagos, BV, James Galloway Speakers bureau: Pfizer, Bristol-Myers Squibb, UCB and Celgene

Background:The Janus kinase-1 preferential inhibitor filgotinib (FIL) improved signs and symptoms of rheumatoid arthritis (RA) in the FIL clinical program.1–3Objectives:To assess FIL safety across regions.Methods:This was an analysis of patients (pts) meeting 2010 ACR/EULAR RA criteria in pooled phase (P)2 DARWIN 1–2 (D1–2), P3 FINCH 1–3 (F1–3), and long-term extension studies (DARWIN 3, FINCH 4). Data were analyzed by region: North America, South and Central America, Western Europe, Eastern Europe, Asia, South East (SE) Asia, and Other. Week (W)12 placebo (PBO)-controlled analysis included data from pts receiving once-daily FIL 100 mg (FIL100), FIL 200 mg (FIL200), or PBO for ≤12W (D1–2, F1–2); long-term as-treated data included pts from all 7 studies receiving FIL100 or FIL200; data after rerandomization were included and contributed to treatment received. Data presented as exposure-adjusted incidence rates (EAIRs)/100 patient-years of exposure (PYE) of treatment-emergent (TE) adverse events (TEAEs).Results:Table 1 shows EAIRs of TEAEs in PBO-controlled analysis. EAIRs/100 PYE of all TEAEs in Western Europe, Asia, and Other were higher than in remaining regions and for PBO vs FIL arms; EAIRs for FIL200/FIL100 in North America and SE Asia were higher vs PBO. EAIRs/100 PYE of TE serious AEs were higher in SE Asia for FIL100 and for FIL200/FIL100 in Other, with high PBO EAIRs in Western Europe. EAIRs/100 PYE of TEAEs leading to study discontinuation were higher in FIL arms vs PBO in Western Europe and Other (FIL200); in Asia and SE Asia, EAIRs were higher for PBO vs FIL200/FIL100.Table 1.EAIR of TEAEs (placebo-controlled)North AmericaN = 481South and Central AmericaN = 350Western EuropeN = 141Eastern EuropeN = 933AsiaN = 236South East AsiaN= 135OtherN = 70TEAEFIL200a216.9 (162.5, 289.5)205.6 (155.1, 272.6)285.0 (188.6, 430.8)150.3 (119.3, 189.4)248.9 (180.6, 343.1)165.1 (104.0, 262.1)298.4 (150.3, 592.5)FIL100b182.2 (136.8, 242.7)159.2 (117.3, 216.1)285.7 (183.7, 444.3)146.4 (115.9, 185.0)246.9 (180.3, 338.1)153.7 (94.2, 251.0)263.5 (113.9, 609.2)PBOC174.5 (130.3, 233.7)162.1 (118.8, 221.2)314.9 (200.7, 493.9)148.4 (117.6, 187.4)259.0 (188.0, 356.8)81.6 (40.8, 163.3)306.0 (142.8, 655.7)TE serious AEFIL200a14.3 (6.0, 34.4)11.4 (3.7, 35.5)8.3 (1.2, 59.0)12.2 (5.2, 28.7)5.5 (0.8, 38.9)0.0 (0.0, ∞)49.6 (10.2, 144.9)FIL100b10.6 (4.0, 28.3)7.2 (1.8, 28.7)19.9 (5.0, 79.7)15.1 (6.8, 33.7)16.2 (5.2, 50.2)28.8 (9.3, 89.4)20.5 (0.5, 114.0)PBOC16.1 (7.2, 35.9)7.5 (1.9, 30.0)29.6 (9.5, 91.7)4.6 (1.3, 15.8)11.4 (2.8, 45.5)10.2 (1.4, 72.4)0.0 (0.0, 69.2)TEAE leading to discontinuationFIL200a8.6 (2.8, 26.6)3.8 (0.1, 21.2)16.6 (4.2, 66.5)12.9 (5.5, 30.5)0.0 (0.0, 20.2)9.2 (1.3, 65.1)16.5 (0.4, 92.1)FIL100b10.6 (4.0, 28.3)7.2 (0.9, 26.0)19.9 (5.0, 79.7)1.9 (0.2, 13.8)5.4 (0.1, 30.1)9.6 (1.4, 68.2)0.0 (0.0, 75.5)PBOC5.4 (1.3, 21.5)0.0 (0.0, 13.8)9.9 (1.4, 70.0)12.9 (5.4, 30.7)17.1 (3.5, 49.9)20.4 (5.1, 81.6)0.0 (0.0, 69.2)Data presented as EAIR (95% CI)/100 patient-yearsaN = 777, 179.8 PYE bN = 788, 181.6 PYE cN = 781, 178.4 PYEA subject may contribute to more than one treatment group if they received more than one treatment of interest.EAIR and corresponding 95% CI were estimated using Poisson regression model by treatment, including study and treatment with an offset of natural log of exposure time, except when 0 events occurred; Poisson model was not adjusted by study.AE, adverse event; CI, confidence interval; EAIR, exposure-adjusted incidence rate; FIL, filgotinib; PBO, placebo; PYE, patient-years of exposure; TE, treatment-emergentFigure shows serious infections (SI), venous thromboembolism (VTE) and herpes zoster (HZ) EAIRs.EAIRs for SI were highest in Other for FIL200 and SE Asia for FIL100. While VTE EAIRs were low, pts in 5/7 regions had VTE. HZ EAIRs were highest in Asia.Conclusion:Although EAIR of TEAEs varied between regions, no consistent trend was reflected in any particular region.References:[1]Genovese et al. JAMA. 2019;322:315–25.[2]Westhovens et al. Ann Rheum Dis. 2021; online first.[3]Combe et al. Ann Rheum Dis. 2021; online first.Disclosure of Interests:Bernard Combe Speakers bureau: BMS; Eli Lilly & Co.; Gilead Sciences, Inc.; MSD; Pfizer; Roche-Chugai; and UCB, Consultant of: AbbVie; Eli Lilly & Co.; Gilead Sciences, Inc.; Janssen; Pfizer; Roche-Chugai; and Sanofi, Grant/research support from: Novartis, Pfizer, and Roche-Chugai, Tsukasa Matsubara Speakers bureau: Pfizer Japan, Nichi-Iko, Astellas, Meiji Seika, Bristol-Myers Squibb, AbbVie GK, Janssen, Chugai, Eisai, AYUMI, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., YingMeei Tan Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Zhaoyu Yin Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Jaehyung Hong Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos, BV, Employee of: Galapagos, BV, Antonio Gomez-Centeno Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly & Co., Gebro, Janssen, Menarini, Merck Sharp & Dohme, Pfizer, Roche, Rubio, Sanofi, and UC, Consultant of: AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Eli Lilly & Co., Gebro, Gilead Sciences, Inc., Hospira, Merck Sharp & Dohme, Pfizer, Roche, Rubio, Sandoz, Sanofi, Grant/research support from: Boehringer Ingelheim, Celltrion, Eli Lilly & Co., Galapagos NV, Gilead Sciences, Inc., Novartis, Pfizer, Roche, Sanofi, UCB, YL Biologics, Maya H Buch Speakers bureau: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB, Consultant of: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB, Grant/research support from: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB

Background:Psoriatic arthritis (PsA) is a heterogeneous, inflammatory disease involving multiple clinical domains including arthritis/synovitis, enthesitis, dactylitis, spondylitis and psoriasis. Effects on each domain should be assessed to determine the overall quality of treatment. Filgotinib (FIL) is a novel preferential Janus kinase 1 inhibitor that is in development for inflammatory conditions including PsA. EQUATOR (NCT03101670) was a 16-week, Phase 2, double-blind, randomised, placebo (PBO)-controlled trial of FIL for patients with active PsA.1 EQUATOR2 (NCT03320876) is an open-label extension (OLE) of the study.Objectives:This post-hoc analysis of EQUATOR and EQUATOR2 assessed the patient-level correlation between changes over time in the three PsA clinical disease domains of skin, joint and enthesitis in patients treated with FIL.Methods:In EQUATOR, patients with active moderate-to-severe PsA (≥5 swollen joints and ≥5 tender joints, fulfilling Classification for PsA criteria) were randomised 1:1 to receive oral FIL 200 mg or PBO once daily (QD) for 16 weeks. At Week 16, patients could continue into the 304-week OLE, with all patients receiving FIL 200 mg QD regardless of previous treatment in EQUATOR. This post-hoc analysis was limited to patients with skin involvement (≥3% body surface area), joint involvement and enthesitis at baseline, with changes from baseline in the three domains assessed using the Psoriasis Area and Severity Index (PASI), swollen/tender joint count (S/TJC), and the Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index, respectively. Analyses that used LEI as the enthesitis index to assess change from baseline included patients with LEI score ≥1 at baseline; those using SPARCC included patients with SPARCC score ≥1 at baseline.Results:The EQUATOR study enrolled 131 patients and 122 patients continued into the EQUATOR2 OLE. Of the 131 patients enrolled in EQUATOR, 49 and 56 patients had PsA involving all three domains at core study baseline when enthesitis was assessed using LEI and SPARCC index, respectively. Pooled data for all patients receiving FIL during the OLE indicate that improvements from baseline in the clinical domains continued with long-term treatment, with 22/42 (52%) and 23/38 (61%) patients having both SJC66 and LEI resolution at Weeks 52 and 100, respectively. For the 22 patients with both SJC and LEI resolution at Week 52, the mean percent change from baseline for PASI was –64%; for the 23 patients with both SJC and LEI resolution at Week 100, the mean percent change from baseline for PASI was –60%. The Figure 1 shows correlation between SJC, LEI and PASI at Week 100. A relationship between the three clinical domains was observed at the individual level; within a single patient, an improvement in one domain was generally followed by improvements in the other two domains. With regard to the sequence in which changes were observed, joints improved first, followed by improvements in the skin and enthesitis. There were no notable differences between changes in LEI and SPARCC enthesitis index in terms of their correlation with improvements in joint and skin involvement. Similarly, there were no notable differences in correlation between the three domains when joints were assessed using TJC rather than SJC.Conclusion:Patients with improvements in skin, joints or enthesitis following treatment with FIL generally also had improvements in the other clinical domains of PsA. The joints were found to be the first of the three domains to improve.References:[1]Mease P et al. Lancet 2018;392:2367–77Acknowledgements:EQUATOR and EQUATOR2 were sponsored by Galapagos NV (Mechelen, Belgium) and co-funded by Galapagos NV and Gilead Sciences, Inc (Foster City, CA, USA). Medical writing/editorial support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), funded by Galapagos NV.Disclosure of Interests:Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer, SUN and UCB, Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, and Pfizer, Filip van den Bosch Consultant of: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Merck and UCB, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Lien Gheyle Shareholder of: Galapagos, Employee of: Galapagos, Mona Trivedi Shareholder of: Gilead Sciences, Amgen, Employee of: Gilead Sciences, Muhsen Alani Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Eline Vetters Employee of: Galapagos, Franck Olivier Le Brun Shareholder of: Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Philip Helliwell Speakers bureau: Janssen and Novartis, Paid instructor for: Pfizer, Consultant of: Eli Lilly.

Background:EQUATOR (NCT03101670) was a Phase 2, double-blind, randomised placebo (PBO)- controlled trial of the preferential Janus kinase 1 inhibitor filgotinib (FIL) for the treatment of psoriatic arthritis (PsA); EQUATOR2 (NCT03320876) is the open-label extension (OLE).Objectives:This post-hoc analysis assessed the effect of FIL on individual Psoriatic Arthritis Disease Activity Score (PASDAS) components; and the association between PASDAS disease activity (DA) levels and DA levels achieved for each PASDAS component and patient-reported outcomes (PROs) up to OLE Week (Wk) 100.Methods:In EQUATOR, patients with active moderate-to-severe PsA were randomised 1:1 to oral FIL 200 mg or PBO once daily (QD) for 16 wks.1 At Wk 16, patients could continue into the 304-wk OLE, in which all patients received FIL 200 mg QD. The proportions of patients with PASDAS of very low DA (VLDA; ≤1.9), LDA (>1.9–Results:At OLE Wk 52, LDA and VLDA were achieved by 27.5% and 16.8% of randomised patients, respectively (44.3% combined). At OLE Wk 100, LDA and VLDA were achieved by 26.0% and 17.6% of patients (43.6% combined; Figure 1). Of patients with HDA at BL, 69% improved to MoDA/LDA/VLDA, Conclusion:The proportion of patients achieving PASDAS VLDA or LDA increased over time and remained stable between OLE Wk 52 and 100. Important factors in determining whether VLDA/LDA was met were PtGDA, PhGDA, and SF-36 PCS, although the low patient numbers is a limitation.References:[1]Mease P, et al. Lancet. 2018;392:2367–77Table 1.Mean % change from baseline in PASDAS components and PROs (observed cases)Core Wk 16 (FIL + PBO groups combined)n=122OLE Wk 52n=110OLE Wk 100n=97VLDAn=8(7%)LDAn=22(18%)Othersn=92(75%)VLDAn=22(20%)LDAn=36(33%)Othersn=52(47%)VLDA n=23(24%)LDAn=34(35%)Othersn=40(41%)PhGDA−93−75−44−94−82−56−96−84−54PtGDA−87−69−13−86−58−24−90−57−13Tender joint count 68−94−80−42−99−84−64−98−87−61Swollen joint count 66−99−80−64−99−96−78−99−94−80LEI−100−86−32−96−100−78−100−99−78Dactylitis−100−100−73−100−100−97−100−100−98C-reactive protein−66−2217138*−32−25−12−1324SF-36 PCS53261133239472316FACIT1195032975134994636HAQ-DI−84−68−18−85−51−18−88−45−19PASI−84−66−29−54−59−56−49−76−42Components or PRO measures in bold are those for which numerical differences between VLDA and LDA are greatest across timepoints*Due to outlier (3784)FACIT, Functional Assessment of Chronic Illness Therapy; HAQ-DI, Health Assessment Questionnaire Disability Index; LEI, Leeds Enthesitis Index; PASI, Psoriasis Area Severity Index; PhGDA, Physician Global Assessment of Disease Activity; PtGDA, Patient Global Assessment of Disease Activity; SF-36 PCS, Short Form-36 physical component summary; (V)LDA, (very) low disease activityAcknowledgements:EQUATOR and EQUATOR2 were sponsored by Galapagos NV Mechelen, Belgium) and co-funded by Galapagos NV and Gilead Sciences, Inc (Foster City, CA, USA). Benjamin Pett and his team, employees of Galapagos, provided assistance with statistical analyses. Medical writing/editorial support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and was funded by Galapagos NV.Disclosure of Interests:Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, and Pfizer, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer, SUN, and UCB, Philip Helliwell Paid instructor for: Janssen, Novartis, and Pfizer, Consultant of: Eli Lilly, Filip van den Bosch Consultant of: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Merck, and UCB, Mona Trivedi Shareholder of: Gilead Sciences, Amgen, Employee of: Gilead Sciences, Muhsen Alani Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Franck Olivier Le Brun Shareholder of: Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Lien Gheyle Shareholder of: Galapagos, Employee of: Galapagos, Emilia Gvozdenovic Employee of: Galapagos, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB., Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.

Introduction Dans la PR, l’EULAR recommande une approche « treat-to-target » avec pour objectif d’atteindre une faible activite ou une remission [1] . Pour les patients, la reduction de la douleur, de la fatigue, la preservation des fonctions physiques et l’amelioration de la qualite de vie (HRQoL) sont egalement des objectifs importants [2] . L’etude FINCH 2 ( NCT02873936 ) a montre que FIL, inhibiteur selectif per os de JAK1, associe a un medicament antirhumatismal synthetique conventionnel (csDMARD) a ameliore de maniere significative (vs PBO) les signes et symptomes de la PR chez des patients presentant une reponse insuffisante a ≥ 1 bDMARD [3] . De plus, une amelioration significative (vs PBO) du HAQ-DI a ete observe a S12 et S24 avec FIL 100 ou 200 mg [3] . Le but de cette analyse est d’evaluer par des questionnaires patients (PRO), l’amelioration de la douleur, de la fatigue et de la qualite de vie sous FIL dans l’etude FINCH 2. Patients et methodes Les patients inclus dans cette etude randomisee en double aveugle ont recu FIL 200 mg (n = 147), FIL 100 mg (n = 153) ou PBO (n = 148) en plus de leur traitement par csDMARD. Les PRO ont ete recueillis de maniere prospective a j1, S2, S4, S8, S12, S14, S16, S20 et S24 pour evaluer la douleur (EVA) ; a j1, S4, S12 et S24 pour evaluer la fatigue (FACIT–Fatigue) et la qualite de vie (SF-36). Resultats Au total, 448 patients ont ete randomises et traites, 381 (85,0 %) ont fini l’etude ( Fig. 1 ). Les valeurs moyennes (ET) des PRO a l’inclusion etaient : 67 (21,0) pour l’EVA douleur, 31 (7,89) pour la composante physique (PCS) du SF-36 et 44,3 (11,6) pour sa composante psychologique (MCS) et 24,4 (11,6) pour le FACIT. Une amelioration significative de l’EVA douleur a debute a S2 et s’est maintenue jusqu’a S24 pour les bras FIL vs PBO. Le score FACIT s’est significativement ameliore a S4, S12, S24 dans le bras FIL 200 mg et a S4 et S12 dans le bras 100 mg. Le sous-score PCS du SF-36 s’est significativement ameliore a S4, S12 et S24 dans les bras FIL vs PBO et le sous-score SF-36 MCS s’est significativement ameliore a S4 et S12 dans le bras FIL 200 vs PBO. Conclusion Associe a un csDMARD, le FIL a permis, chez des patients presentant une reponse insuffisante sous bDMARD, d’ameliorer rapidement et durablement la douleur, la qualite de vie et la fatigue evaluees a l’aide de scores patients valides.

Introduction Les comorbidites et les complications cardiovasculaires sont frequentes dans le rhumatisme psoriasique [1] . L’inhibition des JAK est associee a une augmentation des lipides seriques [2] . Patients et methodes Au cours de l’essai EQUATOR ( NCT03101670 ), 131 patients atteints de rhumatisme psoriasique actif ont recu du FIL 200 mg (n = 65) ou le placebo (PBO) (n = 66) 1 fois/jour pendant 16 semaines. Les patients ayant termine l’essai EQUATOR pouvaient integrer l’extension en ouvert EQUATOR2 ( NCT03320876 ), au cours duquel les patients ont recu du FIL 200 mg pendant une duree maximale de 148 semaines. Les effets du FIL sur le cholesterol total (CT), le HDL-C, le LDL-C et le rapport CT/HDL-C ont ete analyses lors de la semaine 52 de l’etude d’extension (soit 68 semaines apres le debut d’EQUATOR). Dans une analyse post hoc, les patients ont ete classes en sous-groupes selon la presence/l’absence d’obesite (IMC ≥ 30 vs Resultats Cent vingt-quatre patients (95 %) ont termine l’essai EQUATOR. Cent vingt-deux patients (93 %) ont integre EQUATOR2, dont 11 patients (9 %) ont interrompu le traitement avant S52. L’exposition mediane (intervalle) au FIL etait de 66,0 (0,4–104,1) semaines. Au cours d’EQUATOR2, les niveaux de CT, LDL-C et HDL-C ont augmente sous FIL par rapport a l’inclusion, avec pour consequence une baisse du rapport CT/HDL-C. Les variations des parametres lipidiques ont ete coherentes, independamment de la presence d’obesite (n = 56, Fig. 1 ), de DT2 (n = 53), d’HTA (n = 80), d’hyperlipidemie (n = 108) ou d’un syndrome metabolique (n = 36). Chez les patients ayant recu le PBO au cours d’EQUATOR, le taux de HDL-C a augmente sous FIL lors de l’extension en ouvert (de maniere similaire a l’augmentation observee chez les patients traites par FIL pendant EQUATOR). Les niveaux de triglycerides sont restes stables tout au long de l’essai dans tous les sous-groupes. L’effet du FIL sur le profil lipidique des patients prenant un traitement hypolipemiant a ete similaire a celui de la population globale. Conclusion Les effets de l’exposition au FIL pendant ≥ 52 semaines sur le profil lipidique ont ete coherents, quel que soit le risque cardiovasculaire a l’inclusion, avec une hausse du CT et du HDL-C, et une baisse du rapport CT/HDL-C.

Introduction Au cours de l’essai TORTUGA ( NCT03117270 ), etude de phase 2 randomisee en double aveugle, chez des patients atteints de AxSpA, filgotinib (FIL), un inhibiteur selectif de la Janus kinase 1 (JAK1i) per os, a permis d’ameliorer les symptomes ainsi que l’inflammation des ASI et du rachis. Cet essai a egalement montre que FIL permettait de reduire l’activite de la maladie [1] . L’effet des JAKi sur les lesions structurales de l’AxSpA sont inconnus et aucune methode d’analyse de la progression structurale par imagerie n’est etablie. Le but de cette analyse post-hoc etait d’evaluer chez les patients de l’essai TORTUGA, les effets du FIL sur les modifications structurales des ASI mesurees par IRM, selon le score SSS (SIJ Structural Score) developpe par le consortium Spondyloarthritis Research Consortium of Canada (SPARCC). Patients et methodes TORTUGA a suivi 116 patients atteints de AxSpA active, traites par FIL 200 mg (n = 58) ou placebo (PBO) (n = 58) 1 ×/j pendant 12 semaines. Une IRM a ete realisee a l’inclusion et a S12 (ou lors de la derniere consultation de l’etude). Les IRM ont ete reevaluees en post-hoc par 2 experts independants (ignorant la date de l’IRM et le bras de traitement) afin de determiner le score SSS ; les divergences de lectures ont ete arbitrees par un relecteur independant. Les variations du score entre l’inclusion et S12 ont ete evaluees a l’aide d’une analyse de la covariance pour les facteurs suivants : traitement, valeur du score a l’inclusion et stratification de la randomisation. Les moyennes des moindres carres des variations par rapport a l’inclusion et des differences entre les groupes ont ete calculees avec des intervalles de confiances a 95 %. Resultats Les IRM a l’inclusion et a S12 ont ete reevaluees chez 87 patients de l’essai (48 FIL, 39 PBO). Pour les lesions graisseuses et l’ankylose, aucune difference statistiquement significative du score SSS n’a ete observee entre les groupes a S12 (p = 0,17 et 0,46, respectivement). Pour les lesions d’erosion, le score a baisse dans le groupe FIL et augmente dans le groupe PBO (p = 0,02). Les scores relatifs au tissu de comblement ont augmente dans le groupe FIL mais pas dans le groupe placebo (p = 0,005). Conclusion Outre les diminutions de l’inflammation rapportees precedemment, cette analyse post hoc a montre que le FIL (vs PBO) etait associe a une baisse significative des scores d’erosion des ASI, ainsi qu’une augmentation significative des scores relatifs au tissu de comblement a S12. Les effets a long terme restent a determiner.

Introduction EQUATOR ( NCT03101670 ) est un essai de phase 2, randomise, multicentrique, en double aveugle, controle versus placebo, d’une duree de 16 semaines, evaluant l’efficacite du FIL, inhibiteur selectif de la janus kinase-1 per os, chez des patients atteints de rhumatisme psoriasique actif [1] . Cet essai a demontre l’efficacite rapide du FIL versus placebo sur plusieurs parametres, y compris sur le critere de reponse principal ACR20 a 16 semaines [1] . Les patients ayant termine EQUATOR pouvaient integrer l’extension en ouvert d’une duree de 148 semaines (EQUATOR2 ; NCT03320876 ). Cette analyse intermediaire post-hoc predefinie a S52 d’EQUATOR2 a evalue l’efficacite sur differents criteres d’activite de la maladie. Patients et methodes Les patients traites par placebo ont switche pour le FIL (200 mg 1 fois/jour) a S16 et ont integre l’extension en ouvert. Les patients qui recevaient deja FIL ont poursuivi ce traitement. Les profils de reponse ACR20/50/70 a S52 d’EQUATOR2 ont ete evalues selon le Psoriatic Arthritis Disease Activity Score (PASDAS) : faible activite de la maladie (LDA), activite minimale de la maladie (MDA) et MDA/tres faible activite de la maladie (VLDA). Resultats Cent vingt-quatre patients (95 %) ont termine l’essai EQUATOR. Cent vingt-deux patients (93 %) ont integre EQUATOR2, dont 11 patients (9 %) ont interrompu le traitement avant S52. L’exposition mediane (intervalle) au FIL etait de 66,0 (0,4–104,1) semaines. Chez les patients ayant recu initialement le FIL, une efficacite prolongee a ete constatee jusqu’a S52 pour la proportion de patients atteignant une reponse ACR20 (85,1 %), ACR50 (92,6 %), ACR70 (76,9 %), LDA (90,5 %), MDA (76,9 %) et MDA/VLDA (80,0 %). Les donnees PASDAS n’etaient pas disponibles a S16 pour un patient. Une proportion importante de patients n’ayant pas repondu au traitement lors d’EQUATOR a repondu plus tardivement au cours d’EQUATOR2, atteignant le score MDA et le critere ACR50 (22 % et 37 % respectivement). Les profils de reponse lors d’EQUATOR2 etaient similaires, quel que soit le traitement recu precedemment lors d’EQUATOR. Au total, a S52, 33,6 % des patients ont atteint un score MDA et 55,0 % ont atteint une reponse ACR50. Conclusion Ces donnees suggerent que le FIL est susceptible d’apporter une amelioration supplementaire au-dela de 16 semaines chez les patients atteints de rhumatisme psoriasique actif. Son efficacite prolongee a ete demontree a travers plusieurs criteres d’evaluation de l’activite de la maladie, dont le score MDA et l’ACR50.

Introduction Dans le cadre d’un programme clinique compose de 4 essais de Phase 3 (FINCH 1-4 : NCT02889796 , NCT02873936 , NCT02886728 , NCT03025308 ) et 3 essais de Phase 2 (DARWIN 1–3 : NCT01668641 , NCT01894516 , NCT02065700 ), FIL, inhibiteur selectif de JAK1 per os, a entraine une amelioration statistiquement et cliniquement significative des signes et symptomes, de la fonction physique, de la progression radiographique et de la qualite de vie de patients [pts] atteints de PR active 1–3. Patients et methodes Les evenements indesirables apparus sous traitement [EIAST] ont ete integres et presentes pour les pts ayant recu FIL 200 mg 1 fois/j ou FIL 100 mg 1 fois/j (y compris les pts qui ont switche du placebo [PBO], du methotrexate [MTX] ou de l’adalimumab [ADA] ou d’une autre dose de FIL au FIL 100 ou 200 mg/j) ainsi que les pts ayant recu PBO, MTX et ADA dans les 7 etudes. Les taux d’incidence ajustes a l’exposition [TIAE] pour 100 patients-annee [p-a] ont ete calcules pour les evenements indesirables [EI] d’interet de chaque traitement. Resultats Dans les 7 essais, 4057 pts atteints de PR (2227 pts FIL 200 mg, 1600 pts FIL 100 mg, 325 pts ADA, 416 pts MTX et 781 pts PBO) ont recu > 1 dose de traitement pour une exposition totale de 5493 p-a. Les TIAE des EI graves et des EIAST entrainant le deces chez les patients ayant recu FIL ont ete comparables a ceux des patients ayant recu PBO, ADA ou MTX, sans effet dose-dependant. Le TIAE du zona a ete globalement faible, numeriquement superieur sous FIL a ADA et PBO, similaire au MTX : TIAE FIL 200 mg : 1,7 ; intervalle de confiance [IC] a 95 % : 1,3-2,3, FIL 100 mg : 1,1 ; IC : 0,7-1,8, ADA : 0,7 ; IC : 0,2-2,8, MTX : 1,1 ; IC : 0,4-3,0, PBO : 1,0 ; IC : 0,3-3,1. Les TIAE des infections graves ont ete comparables entre FIL 100 mg (3,3 ; IC : 2,2-4,9) et ADA (3,4 ; IC : 1,9-6,4), et numeriquement inferieurs pour FIL 200 mg (1,7 ; IC : 1,3-2,3) et MTX (2,2 ; IC : 1,1-4,5). Les taux d’infections opportunistes (y compris la tuberculose active) ont ete globalement faibles ; les TIAE pour FIL 100 mg (0,3 ; IC : 0,1-0,7) et FIL 200 mg (0,1 ; IC : 0,0-0,3) ont ete comparables au PBO et numeriquement inferieurs a ADA (0,7 ; IC : 0,2-2,8) ou MTX (0,6 ; IC : 0,1-2,2). Les taux d’evenements cardiovasculaires indesirables graves et de thromboembolie veineuse ont ete numeriquement inferieurs sous FIL vs PBO. Les tumeurs malignes, y compris les cancers de la peau hors melanomes, ont ete globalement rares, et les taux ont ete faibles chez les patients ayant recu FIL. Conclusion FIL a ete bien tolere et aucune nouvelle toxicite n’a ete identifiee. Les resultats de tolerance sont concordants avec l’inhibition selective de JAK1 et mettent en avant le profil de tolerance favorable du FIL chez les patients atteints de PR.

Background:EQUATOR (NCT03101670) was a 16-week, Phase 2, multicenter, double-blind, placebo-controlled, randomized controlled trial (RCT) of filgotinib in patients with active psoriatic arthritis.1Filgotinib demonstrated rapid efficacy compared with placebo across multiple domains, including the primary endpoint of Week 16 American College of Rheumatology (ACR) 20 response.1Patients completing the RCT could join an ongoing 148-week OLE (EQUATOR2;NCT03320876).Objectives:In this prespecified interim analysis at Week 52 of the OLE, individual patient responses with respect to disease activity were evaluated.Methods:Placebo-treated RCT patients switched to filgotinib (200 mg once daily) at Week 16 and entered the OLE; patients previously assigned to filgotinib continued. Individual response patterns at Week 52 of the OLE were evaluated for ACR20/50/70, Psoriatic Arthritis Disease Activity Score (PASDAS) low disease activity (LDA), minimal disease activity (MDA), and MDA/very low disease activity (VLDA).Results:124 patients (95%) completed EQUATOR; 122 (93%) enrolled in the OLE. At Week 52, 11 patients (9%) had discontinued treatment in the OLE. Median (range) exposure to filgotinib was 66.0 (0.4–104.1) weeks. In patients originally assigned to filgotinib, sustained efficacy was seen through to OLE Week 52 for ACR20, 50, and 70; PASDAS LDA; MDA (Table;Figure 1a); and MDA/VLDA. In total, 77% and 93% of those achieving MDA and ACR50 response in the RCT period maintained this at Week 52 (Table). A substantial proportion of RCT non-responders also achieved a treatment response in the OLE, meeting MDA and ACR50 criteria (22% and 37%, respectively;Table). Response patterns in the OLE were similar regardless of prior RCT treatment. In total, at Week 52 of the OLE, 33.6% of patients achieved MDA response (Figure 1a); 55.0% achieved ACR50 response. Figure 1bshows individual patient response over time for MDA.Conclusion:Data from this 52-week OLE interim analysis suggest that further improvement in disease activity can be expected with filgotinib beyond 16 weeks in patients with active psoriatic arthritis. Sustained efficacy was demonstrated across several measures of disease activity, including MDA and ACR50.References:[1]Mease P, et al. Lancet 2018;392:2367–77.Table.Responders at Week 52 of the OLE, by treatment and previous RCT responder status (observed cases).TreatmentFilgotinib (N=59) → Filgotinib (N=54)aPlacebo (N=63) → Filgotinib (N=57)an/N, %OLE responders/RCT respondersOLE responders/RCT non-respondersOLE responders/RCT respondersOLE responders/RCT non-respondersACR2040/47 (85.1)5/7 (71.4)17/18 (94.4)27/38 (71.1)ACR5025/27 (92.6)10/27 (37.0)5/8 (62.5)21/49 (42.9)ACR7010/13 (76.9)12/41 (29.3)3/4 (75.0)12/53 (22.6)PASDAS LDAb19/21 (90.5)12/32 (37.5)5/6 (83.3)21/48 (43.8)MDA10/13 (76.9)9/41 (22.0)4/5 (80.0)14/51 (27.5)aIndicates number remaining at OLE Week 52 interim analysis, after dropoutsbPASDAS information was not available for one patient at Week 16 of the RCTAcknowledgments:EQUATOR and EQUATOR2 were sponsored by Galapagos NV and co-funded by Galapagos NV and Gilead Sciences. Medical writing support was provided by Hannah Mace MPharmacol, CMPP (Aspire Scientific Ltd, Bollington, UK) and funded by Galapagos NV.Disclosure of Interests:Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Laura C Coates: None declared, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Philip Helliwell: None declared, Chantal Tasset Shareholder of: Galapagos (share/warrant holder), Employee of: Galapagos, Luc Meuleners Employee of: Galapagos, Leen Gilles Consultant of: Galapagos, Lien Gheyle Employee of: Galapagos, Mona Trivedi Shareholder of: Amgen and Gilead Sciences, Employee of: Gilead Sciences, Muhsen Alani Employee of: Gilead Sciences, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Background:Ankylosing spondylitis (AS) is a chronic, immune-mediated disease characterized by inflammation of the sacroiliac joints and spine, and a young age of onset of 20–40 years. In the recent TORTUGA study, filgotinib (FIL), an oral, selective Janus kinase 1 (JAK1) inhibitor, significantly reduced AS disease activity compared with placebo (PBO).1Selective JAK1 inhibition by FIL has the potential to simultaneously block multiple inflammatory pathways, thus we analyzed biomarker concentrations in serum samples from TORTUGA.Objectives:To evaluate the impact of selective JAK1 inhibition with FIL on circulating disease associated biomarkers in adult patients with active AS enrolled in the TORTUGA study.Methods:TORTUGA (Clinicaltrials.gov identifierNCT03117270) was a 12-week, randomized, double-blind, placebo-controlled, phase 2 study. Patients were randomized 1:1 to FIL 200 mg (n=58) or PBO (n=58) once-daily. Serum samples (FIL n=56, PBO n=53) were collected at baseline (BL) and weeks 1, 4 and 12, and analyzed using the Meso Scale Discovery immunoassay platform (Meso Scale Diagnostics, Rockville, MD, USA) to evaluate 135 biomarkers. Biomarker concentration changes from BL were analyzed on paired patient data and reported for weeks 1, 4 and 12, and clustering analysis was performed. Correlation between the 135 biomarkers and selected clinical scores at BL was assessed by Spearman rank correlation analysis.Results:FIL treatment produced significant reductions in serum concentrations of multiple biomarkers associated with AS disease activity. Five clusters of biomarker response were identified based on the kinetics and magnitude of percent changes from BL. These clusters also represented discrete biological functions: cluster 1 (rapid, strong >50% decrease in all three time points) included systemic inflammation biomarkers eg, CRP, SAA; cluster 2 (>20% decrease in at least one time point) included immune cell biomarkers eg, MIP3B, IL12p40; cluster 3 (Spearman rank correlation analyses showed that at BL, the systemic inflammation biomarkers CRP and SAA, as well as a number of biomarkers including ICAM-1 and MMP3, were positively correlated with BL AS disease activity score (ASDAS); conversely, only a few biomarkers showed a negative correlation with BL ASDAS, the cytokine receptor FLT3 and the chemotactic cytokine fractalkine (FRACTAL).Conclusion:In patients with active AS, FIL treatment significantly decreased levels of circulating biomarkers associated with active AS disease, including proinflammatory cytokines and chemokines, cell adhesion molecules, and markers of matrix remodelling. Clustering analysis revealed early and late biomarker changes associated with disease. These data are consistent with reduced AS disease activity in TORTUGA and suggest that FIL treatment leads to a rapid and sustained reduction of inflammation in AS.References:[1]van der Heijde Det al. Lancet2018;392:2378–87Acknowledgments:This study was funded by Gilead Sciences, Inc. Editorial support was provided by Fishawack Communications Inc and funded by Gilead Sciences, Inc.Disclosure of Interests:Walter P. Maksymowych Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, and UCB, Yuan Tian Employee of: Gilead Sciences Inc., Oh Kyu Yoon Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., William Barchuk Shareholder of: Gilead Sciences Inc and Eli Lilly, Employee of: Current employee of Gilead Sciences Inc and a former employee of AbbVie, Eli Lilly, and Johnson & Johnson, René Galien Shareholder of: Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Yihua Liu Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Amer M. Mirza Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Vlad Malkov Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Angie Hertz Shareholder of: Gilead Sciences Inc, Employee of: Gilead Sciences Inc

Background:Filgotinib, an oral selective Janus kinase (JAK) 1 inhibitor, reduced disease activity and improved symptoms and inflammation of the sacroiliac joint (SIJ) and spine in patients with active axial ankylosing spondylitis (AxSpA) in the Phase 2 TORTUGA trial (NCT03117270).1The effects of JAK inhibitors on structural lesions in active AxSpA are unknown and optimal methods for image analysis of structural disease progression are not established.Objectives:The aim of this post hoc analysis was to evaluate the effects of filgotinib on magnetic resonance imaging (MRI) measures of structural changes in the SIJ in patients from the TORTUGA trial, as assessed by Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ Structural Scores (SSS).Methods:TORTUGA was a multicenter, double-blind, randomized trial of 116 patients with active AxSpA treated with filgotinib 200 mg (n=58) or placebo (n=58) once daily for 12 weeks. MRI was conducted at baseline and Week 12 (or early discontinuation visit). MRIs were re-evaluated post hoc by two independent experts (blinded to time point and assigned treatment) to determine SPARCC SSS; inter-reader discrepancies were resolved by an independent adjudicator. Observed changes from baseline were evaluated using analysis of covariance with factors for treatment, baseline value, and randomization stratification. Least-squares mean changes from baseline and between-group differences with 95% confidence intervals were calculated.Results:MRI scans from 87 patients with an evaluable MRI at baseline and Week 12 (or early termination visit) were re-evaluated (48 filgotinib, 39 placebo). Erosion scores decreased in the filgotinib group and increased in the placebo group (p=0.02 for between-group difference; Table 1; Figure 1a). Backfill scores increased in the filgotinib group but not in the placebo group (p=0.005; Table 1; Figure 1b). There was no statistically significant between-group difference in SSS total ankylosis (p=0.46) or fat lesion (p=0.17) changes from baseline (Table 1).Table 1.Summary of Spondyloarthritis Research Consortium of Canada Sacroiliac Joint Structural Scores.ScoreMean (SD) BL scoreLSM change from BL (95% CI) at Week 12LSM group difference at Week 12 (95% CI)Erosion FIL 200 mg3.38 (5.34)–0.46 (–1.31, 0.40)–1.01 (–1.87, –0.16) PBO2.62 (3.76)0.56 (–0.31, 1.42)[p=0.02]Backfill FIL 200 mg1.02 (1.99)0.76 (0.07, 1.45)1.02 (0.32, 1.72) PBO1.35 (2.59)–0.26 (–0.97, 0.45)[p=0.005]Fat metaplasia FIL 200 mg4.19 (6.06)0.37 (–0.23, 0.97)0.43 (–0.18, 1.03) PBO4.35 (5.44)–0.06 (–0.67, 0.56)[p=0.17]Ankylosis FIL 200 mg9.58 (8.15)0.14 (–0.02, 0.30)0.06 (–0.10, 0.22) PBO9.83 (8.45)0.08 (–0.08, 0.25)[p=0.46]BL, baseline; CI, confidence interval; FIL, filgotinib; LSM, least-squares mean; PBO, placebo; SD, standard deviationConclusion:In addition to previously reported decreases in SPARCC inflammation, filgotinib was associated with significant reduction in SIJ erosion scores and increase in backfill scores at Week 12 of the TORTUGA trial, versus placebo. Long-term effects are to be determined.References:[1]van der Heijde D, et al. Lancet 2018;392:2378–87.Acknowledgments:We thank Robert Lambert for his review of the MRI scans in the role of adjudicator. The TORTUGA trial was sponsored by Galapagos NV and co-funded by Galapagos NV and Gilead Sciences. Medical writing support was provided by Hannah Mace MPharmacol, CMPP (Aspire Scientific Ltd, Bollington, UK) and funded by Galapagos NV (Mechelen, Belgium).Disclosure of Interests:Walter P. Maksymowych Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, and UCB, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Robert B.M. Landewé Consultant of: AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Co.; Galapagos NV; Novartis; Pfizer; UCB Pharma, William Barchuk Shareholder of: Gilead Sciences Inc and Eli Lilly, Employee of: Current employee of Gilead Sciences Inc and a former employee of AbbVie, Eli Lilly, and Johnson & Johnson, Ke Liu Shareholder of: Gilead Sciences Inc (stockholder), Employee of: Gilead Sciences Inc, Chantal Tasset Shareholder of: Galapagos (share/warrant holder), Employee of: Galapagos, Leen Gilles Consultant of: Galapagos, Thijs Hendrikx Shareholder of: Galapagos (share/warrant holder), Employee of: Galapagos, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen

Background:Cardiovascular (CV) comorbidities are common in psoriatic arthritis (PsA); patients are at high risk for major adverse cardiovascular events (MACE).1In the Phase 2, double-blind, randomized EQUATOR trial, significant improvements across multiple PsA domains were observed with the oral selective Janus kinase (JAK) 1 inhibitor filgotinib compared with placebo.2Inhibition of JAK signal transducer and activator of transcription signaling is associated with raised serum lipids.3Objectives:To evaluate the effects of filgotinib on the lipid profile of PsA patients and determine if those with higher MACE risk show similar changes in lipid profile compared with the overall population.Methods:In EQUATOR, 131 patients with active PsA received filgotinib 200 mg (n=65) or placebo (n=66) once daily for 16 weeks. Patients completing EQUATOR could enter the ongoing EQUATOR2 open-label extension (OLE;NCT03320876), in which patients receive filgotinib 200 mg for up to 148 weeks. Effects of filgotinib on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and TC/HDL-C ratio at OLE Week 52 (68 weeks after EQUATOR initiation) were analyzed. In a post hoc analysis, patients were classified into subgroups according to presence/absence of obesity (baseline body mass index [BMI]; ≥30 vs 2, respectively), diabetes mellitus, arterial hypertension (≥130/80 mmHg), hyperlipidemia, and metabolic syndrome. Changes in lipid levels were explored graphically.Results:124 patients (95%) completed EQUATOR; 122 (93%) enrolled in the OLE. Of these, 11 patients (9%) discontinued treatment by OLE Week 52. Median (range) exposure to filgotinib was 66.0 (0.4–104.1) weeks. In the OLE, TC, LDL-C, and HDL-C levels increased versus baseline with filgotinib, resulting in a decreased TC/HDL-C ratio. Changes in lipid levels were consistent irrespective of presence of obesity (n=56;Fig), diabetes (n=53), arterial hypertension (n=80), hyperlipidemia (n=108), or metabolic syndrome (n=36); baseline lipid values were greater in the higher risk groups. In patients who were assigned placebo in the randomized controlled trial (RCT), HDL-C increased on switching to filgotinib in the OLE (in a manner similar to that seen in filgotinib-treated patients during the RCT), and remained elevated compared with baseline (Fig). Triglyceride levels remained stable throughout, across all subgroups. Seventeen patients (13%) were taking lipid-lowering drugs (LLDs) prior to the start of the trial (and continued to do so); the effect of filgotinib on the lipid profile in these patients was similar to that in the overall population. During the RCT phase, another six patients in the filgotinib group and one in the placebo group began taking LLDs.Conclusion:In patients exposed to filgotinib for ≥52 weeks, the effects on lipid profile were consistent regardless of baseline CV risk. Lipid changes included an elevation in TC and HDL-C, with a decrease in TC/HDL-C ratio.References:[1]Haddad A & Zisman D. Rambam Maimonides Med J 2017;8:e0004[2]Mease P, et al. Lancet 2018;392:2367–77[3]Sands B, et al. Clin Gastroenterol Hepatol 2020;18:123–32Acknowledgments:Studies were sponsored by Galapagos NV; co-funded by Galapagos NV and Gilead Sciences. Writing support from Hannah Mace MPharmacol, CMPP (Aspire Scientific Ltd, Bollington, UK) was funded by Galapagos NV (Mechelen, Belgium).Disclosure of Interests:M Elaine Husni Grant/research support from: Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Regeneron, and UCB, Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Philip Helliwell: None declared, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Chantal Tasset Shareholder of: Galapagos (share/warrant holder), Employee of: Galapagos, Luc Meuleners Employee of: Galapagos, Leen Gilles Consultant of: Galapagos, Lien Gheyle Employee of: Galapagos, Mona Trivedi Shareholder of: Amgen and Gilead Sciences, Employee of: Gilead Sciences, Muhsen Alani Employee of: Gilead Sciences, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Background:In the FINCH 1 study, filgotinib (FIL)—an oral, potent, selective Janus kinase 1 inhibitor—in combination with methotrexate (MTX) provided significant improvements in the signs and symptoms of rheumatoid arthritis (RA) in patients (pts) with inadequate response to MTX.1While EULAR guidelines recommend a treat-to-target approach focusing on reducing inflammation to prevent joint damage, physical disability, and mortality, pts consider control of pain and fatigue, along with maintenance of physical function and health-related quality of life (HRQoL), to be important aspects for their care.2,3Objectives:To evaluate the rate and magnitude of change in patient-reported outcomes (PROs) from FINCH 1.Methods:In the FINCH 1 study (NCT02889796), pts with active RA received oral FIL 200 mg + MTX, FIL 100 mg + MTX, PBO + MTX, or subcutaneous adalimumab (ADA) 40 mg + MTX for up to 52 weeks (W); pts receiving PBO at W24 were rerandomised 1:1 to FIL 100 or 200 mg. PROs included the HAQ-DI and VAS pain scale, SF-36, and FACIT-Fatigue questionnaire. The change from baseline (CFB) at each time point was assessed up to W52 for each treatment group. The mixed-effects model for repeated measures was used to compare each FIL group with PBO for the CFB at each time point through W24. The logistic regression model was used to compare each FIL group with PBO for the proportion of pts achieving the minimum clinically important difference (MCID) of ≥0.22 reduction in CFB in HAQ-DI at each time point through W24.Results:Of 1755 pts randomised and treated (475 FIL 200 mg + MTX; 480 FIL 100 mg + MTX; 325 ADA + MTX; and 475 PBO + MTX), 1417 (80.7%) received study drug through W52. As early as W2 through W24, pts receiving either dose of FIL experienced nominally significantly greater (p A, B). At W2, compared with PBO (40.2%), a nominally significantly greater proportion of pts achieved the HAQ-DI MCID in both the FIL 200 (52.5%; p A, B). By W4, pts receiving either dose of FIL reported a nominally significantly greater mean CFB in FACIT-Fatigue scores vs PBO (p C). In general, CFB for HAQ-DI, VAS pain scale, and FACIT-Fatigue observed for the FIL groups was higher or comparable to ADA at various time points (Fig 1, 2).Conclusion:Both doses of FIL provided rapid and sustained improvements in functional status, pain, HRQoL, and fatigue compared with PBO for pts with RA and inadequate response to MTX throughout the 52-week period.References:[1]Combe BG, et al.Ann Rheum Dis.2019;78 (Suppl 2):A77.[2]Fautrel B, et al.Rheumatol Int.2018;38:935–47.[3]Smolen JS, et al.Ann Rheum Dis.2017;76:960–77.Disclosure of Interests:Alan Kivitz Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim,,Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Susan Lee Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Lei Ye Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Hao Hu Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB

Background:The oral, potent, selective JAK1 inhibitor filgotinib (FIL) showed favorable efficacy at week (W)12 and W24 of treatment for rheumatoid arthritis (RA) compared with methotrexate (MTX) monotherapy (mono) in FINCH 3 (NCT02886728) and with placebo (PBO) or adalimumab (ADA) in FINCH 1 (NCT02889796).Objectives:50% clinical improvement from baseline at W12 is a key checkpoint for RA treatment.1These post hoc analyses evaluated FIL treatment effect on improvement in ACR components at W12 and remission at W24 in FINCH 3 and FINCH 1.Methods:FINCH 3 and FINCH 1 were global, phase 3, double-blind studies in patients (pts) with active RA. In FINCH 3, MTX-naïve pts were randomised 2:1:1:2 to once-daily (QD) oral FIL 200 mg + weekly MTX, FIL 100 mg + MTX, FIL 200 mg mono + PBO, or PBO + MTX mono up to W52. In FINCH 1, pts with inadequate response to MTX (MTX-IR) on a background of stable MTX were randomised (3:3:2:3) to oral FIL 200 or 100 mg QD, subcutaneous ADA 40 mg Q2W, or PBO up to W52. Post hoc analyses evaluated proportions of pts with 50% improvement from baseline in each ACR component and in all 7 ACR components (ACR50c) at W12, and proportions of pts with ACR50c at W12 achieving clinical remission at W24. Comparisons between treatments were not adjusted for multiplicity; subgroup comparisons are descriptive.Results:Analyses included 1249 pts in FINCH 3 and 1755 pts in FINCH 1. Greater proportions of pts receiving FIL 200 mg + MTX, FIL 100 mg + MTX, or FIL mono (FINCH 3) vs MTX mono (FINCH 3) or PBO + MTX (FINCH 1)—and numerically higher proportions of pts receiving FIL 200 mg + MTX vs FIL 100 mg + MTX (both studies) or ADA + MTX (FINCH 1)—achieved ACR50c and individual components at W12 (Table). Proportions of pts achieving CDAI ≤2.8 (Figure 1) or Boolean remission (Figure 2) at W24 were higher for pts with vs without ACR50c at W12 (Figures 1–2).Table.Proportions of patients with 50% improvement in each ACR component and ACR50c at week 12ACR componentSJC66TJC68PainPGASGAHAQ-DIhsCRPACR50cFINCH 3FIL 200 mg + MTX82.2***76.9***59.2***72.8***56.5***54.9***59.1***26.2***FIL 100 mg + MTX81.2***74.4***48.5*68.1*46.9**49.5***58.5***19.3***FIL 200 mg mono82.9***75.7***47.6*66.2*47.1**47.3**59.5***22.9***MTX mono67.159.639.258.435.635.633.76.0FINCH 1FIL 200 mg + MTX83.2***,+77.9***,+50.1***,+67.4***48.2***42.1***,+67.2***,+++18.5***FIL 100 mg + MTX77.9***72.3***45.1***62.9***43.2***35.2***55.0***12.5***ADA + MTXa76.970.541.561.542.034.455.713.8PBO + MTX66.759.228.050.928.023.125.92.5aNot formally compared vs PBO + MTX.*, p **, p ***, p +, p +++, p ACR50c, 50% improvement from baseline in all ACR components; ADA, adalimumab; FIL, filgotinib; MTX, methotrexate; mono, monotherapy; PBO, placebo.Conclusion:In MTX-naïve and MTX-IR pts with RA, FIL treatment was more effective vs MTX (FINCH 3) or PBO (FINCH 1) for achieving ACR50c at W12—a potential predictor of remission at W24. Proportions of pts achieving ACR50c at W12 were numerically higher for pts receiving FIL 200 mg + MTX vs FIL 100 mg + MTX (both studies) or ADA + MTX (FINCH 1).References:[1]Smolen JS, et al.Ann Rheum Dis. 2017;76:960–77.Disclosure of Interests:Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Daniel Aletaha Grant/research support from: AbbVie, Novartis, Roche, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Patrick Durez Speakers bureau: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Pfizer, Sanofi, Antonio Gomez-Centeno: None declared, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Beatrix Bartok Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Franziska Matzkies Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Lei Ye Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Zhaoyu Yin Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, William Rigby Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Genentech, Pfizer, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB

Background:Treatment with the oral selective Janus kinase 1 inhibitor filgotinib was associated with rapid and significant improvements in multiple domains of active psoriatic arthritis versus placebo in the 16-week Phase 2, multicenter, double-blind, randomized EQUATOR trial (NCT03101670).1A significantly greater proportion of patients receiving filgotinib, versus placebo, achieved the primary endpoint of 20% improvement in American College of Rheumatology (ACR) 20 response at Week 16 (80% vs 33%, respectively).1Objectives:The aim of this predefined analysis was to evaluate the consistency of the response to filgotinib across predefined relevant subpopulations participating in the EQUATOR trial.Methods:In EQUATOR, patients with active psoriatic arthritis were treated with filgotinib 200 mg (n=65) or placebo (n=66) once daily for 16 weeks. Key clinical endpoints, including ACR20 and ACR50 (50% improvement) response rates, Psoriatic Arthritis Disease Activity Score (PASDAS), and Disease Activity Index for Psoriatic Arthritis (DAPSA) were evaluated according to the following baseline characteristics: sex, body mass index, disease duration, baseline disease severity, concurrent use of disease-modifying antirheumatic drug(s), and prior exposure to tumor necrosis factor inhibitor(s). For PASDAS and DAPSA scores, statistical analysis of changes from baseline was performed using analysis of covariance with factors for treatment, randomization stratification, subgroup, and an interaction between treatment and subgroup. Least-squares (LS) mean difference between treatment arms and the corresponding 95% confidence intervals (CI) were calculated. For ACR20 and ACR50 response rates, statistical analysis used the point estimate and corresponding 95% CI, based on the Newcombe method.Results:Sixty patients (92%) in the filgotinib group and 64 (97%) in the placebo group completed the study. The total number of patients in each subpopulation ranged from 18 to 104 (Figure 1). Differences in the proportions of patients achieving ACR20 consistently favored filgotinib, compared with placebo, across all subgroups (Figure 1); all differences reached statistical significance. Similarly, differences in the proportions of ACR50 responders and LS mean treatment differences for PASDAS and DAPSA consistently favored filgotinib, reaching statistical significance in most subgroups. No clinically relevant differences in the effect of filgotinib were observed across subgroups. Filgotinib was generally well tolerated and no new safety signals were identified.Conclusion:In the 16-week EQUATOR trial, the effects of filgotinib on key efficacy endpoints were generally consistent across a range of subgroups based on patient, disease, and treatment characteristics.References:[1]Mease P, et al. Lancet 2018;392:2367–77.Acknowledgments:The EQUATOR trial was sponsored by Galapagos NV and co-funded by Galapagos NV and Gilead Sciences. Medical writing support was provided by Hannah Mace MPharmacol, CMPP (Aspire Scientific Ltd, Bollington, UK) and funded by Galapagos NV (Mechelen, Belgium).Disclosure of Interests:Philip Helliwell: None declared, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Laura C Coates: None declared, Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Chantal Tasset Shareholder of: Galapagos (share/warrant holder), Employee of: Galapagos, Luc Meuleners Employee of: Galapagos, Leen Gilles Consultant of: Galapagos, Lien Gheyle Employee of: Galapagos, Mona Trivedi Shareholder of: Amgen and Gilead Sciences, Employee of: Gilead Sciences, Muhsen Alani Employee of: Gilead Sciences, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Background Filgotinib (FIL) is an oral, selective Janus Kinase 1 inhibitor under development for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. Safety and efficacy of FIL was investigated in the FINCH clinical program, which includes three Phase 3, randomised, multicentre studies in patients with moderate to severely active RA. FINCH1: patients with inadequate response to MTX (NCT02889796); FINCH2: patients receiving conventional disease-modifying antirheumatic drugs (csDMARDs) with inadequate response to biological DMARDs (NCT02873936); FINCH3: MTX-naïve patients initiating MTX ± FIL, or receiving FIL monotherapy (NCT02886728). We present pooled safety data up to 24 weeks (W24). Methods The FINCH studies enrolled patients with RA (2010 ACR/EULAR criteria), ≥6 swollen joints and ≥6 tender joints at screening and Day 1. Safety analyses included patients receiving ≥1 dose of study drug. Patients in FINCH 1 and 2 who did not experience at least a 20% improvement in both swollen joint count and tender joint count by W14 discontinued study drug and switched to a standard of care. W24 safety data from all studies were aggregated and summarised. Key safety endpoints were treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of interest, deaths and treatment-emergent laboratory abnormalities. Results 3452 patients were evaluated; 2088 received FIL. At W24, the frequency of TEAEs and TEAEs of interest were similar for those who received FIL and those in the control groups (Table 1). Most TEAEs were infections. Laboratory abnormality rates were similar between FIL and control groups, and were mild to moderate (grades 1 and 2). Overall, the frequency of major adverse cardiac events, herpes zoster virus, deep vein thrombosis and pulmonary embolism was low, and similar across groups. Conclusion Pooled data from this large database highlights the favourable safety and tolerability profile of FIL in patients with RA both as monotherapy and in combination with MTX/csDMARD.

The Janus kinase 1 (JAK1) pathway has been implicated in the pathogenesis of psoriatic arthritis. We aimed to investigate the efficacy and safety of filgotinib, a selective JAK1 inhibitor, for the treatment of psoriatic arthritis.The EQUATOR trial was a randomised, double-blind, placebo-controlled phase 2 trial that enrolled adults from 25 sites in seven countries (Belgium, Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine). Patients (aged ≥18 years) had active moderate-to-severe psoriatic arthritis (defined as at least five swollen joints and at least five tender joints) fulfilling Classification for psoriatic arthritis (CASPAR) criteria, active or a documented history of plaque psoriasis, and an insufficient response or intolerance to at least one conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). Patients continued to take csDMARDs during the study if they had received this treatment for at least 12 weeks before screening and were on a stable dose for at least 4 weeks before baseline. Using an interactive web-based system, we randomly allocated patients (1:1) to filgotinib 200 mg or placebo orally once daily for 16 weeks (stratified by current use of csDMARDs and previous use of anti-tumour necrosis factor). Patients, study team, and sponsor were masked to treatment assignment. The primary endpoint was proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR20) at week 16 in the full analysis set (patients who received at least one dose of study drug), which was compared between groups with the Cochran-Mantel-Haenszel test and non-responder imputation method. This trial is registered with ClincalTrials.gov, number NCT03101670.Between March 9, and Sept 27, 2017, 191 patients were screened and 131 were randomly allocated to treatment (65 to filgotinib and 66 to placebo). 60 (92%) patients in the filgotinib group and 64 (97%) patients in the placebo group completed the study; five patients (8%) in the filgotinib group and two patients (3%) in the placebo group discontinued treatment. 52 (80%) of 65 patients in the filgotinib group and 22 (33%) of 66 in the placebo group achieved ACR20 at week 16 (treatment difference 47% [95% CI 30·2-59·6], p0·0001). 37 (57%) patients who received filgotinib and 39 (59%) patients who received placebo had at least one treatment-emergent adverse event. Six participants had an event that was grade 3 or worse. The most common events were nasopharyngitis and headache, occurring at similar proportions in each group. One serious treatment-emergent adverse event was reported in each group (pneumonia and hip fracture after a fall), one of which (pneumonia) was fatal in the filgotinib group.Filgotinib is efficacious for the treatment of active psoriatic arthritis, and no new safety signals were identified.Galapagos and Gilead Sciences.

Background: At present, biological disease-modifying anti-rheumatic drugs (DMARDs) are the only treatment recommended for patients with ankylosing spondylitis who have not responded to first-line treatment with non-steroidal anti-inflammatory drugs (NSAIDs). The TORTUGA trial investigated the efficacy and safety of filgotinib, an oral selective Janus kinase 1 (JAK1) inhibitor, for the treatment of patients with active ankylosing spondylitis. Methods: In this completed, randomised, double-blind, placebo-controlled, phase 2 trial, we enrolled adult patients from 30 sites in seven countries (Belgium, Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine). Eligible patients had active ankylosing spondylitis and an inadequate response or intolerance to two or more NSAIDs. Patients were randomly assigned (1:1) with an interactive web-based response system to receive filgotinib 200 mg or placebo orally once daily for 12 weeks. Randomisation was stratified by current use of conventional synthetic DMARDs and previous receipt of anti-tumour necrosis factor therapy. The patients, study team, and study sponsor were masked to treatment assignment. The primary endpoint was the change from baseline in ankylosing spondylitis disease activity score (ASDAS) at week 12, which was assessed in the full analysis set (ie, all randomised patients who received at least one dose of study drug). Safety was assessed according to actual treatment received. This trial is registered with ClinicalTrials.gov, number NCT03117270. Findings: Between March 7, 2017, and July 2, 2018, 263 patients were screened and 116 randomly assigned to filgotinib (n=58) or placebo (n=58). 55 (95%) patients in the filgotinib group and 52 (90%) in the placebo group completed the study; three (5%) patients in the filgotinib group and six (10%) in the placebo group discontinued treatment. The mean ASDAS change from baseline to week 12 was −1·47 (SD 1·04) in the filgotinib group and −0·57 (0·82) in the placebo group, with a least squares mean difference between groups of −0·85 (95% CI −1·17 to −0·53; p

Background Filgotinib (FIL) is an oral, selective Janus kinase inhibitor, shown to be effective and well tolerated in patients (pt) with rheumatoid arthritis (RA) and other inflammatory diseases (IBD/AS/PsA). DARWIN 3, an ongoing, open-label, long-term extension of phase 2b studies evaluates the longer-term safety and efficacy of FIL in RA. Methods The study evaluated pt outcomes for methotrexate (MTX) inadequate responders completing the 24-week DARWIN 1 (FIL+MTX) and DARWIN 2 (FIL monotherapy) studies. We present an interim analysis at week 156 following FIL 200 or 100 mg/day treatment. Event rate: total events/total years of exposure of FIL; Exposure: until data cut-off in patients on the study at the time of analysis. Results Eight hundred and seventy-seven patients completed the parent studies. Seven hundred and thirty-nine enrolled in DARWIN 3 (497 DARWIN 1, 242 DARWIN 2); most DARWIN 1 and 2 patients were female (81.5%, 81.8%), white (75.3%, 74.8%); mean age was 53 and 52 years, respectively. Mean baseline MTX dose in the FIL+MTX group: 16.8mg/week. At week 156, 59.9% of patients remained on study. Most common reasons for discontinuation were adverse events (26.5%) and subject request (9.1%). Total exposure to FIL was 2203 pt-years; mean exposure ± standard deviation (SD): 3.04 ± 1.22 years for FIL+MTX and 2.86 ± 1.21 years for FIL monotherapy. Treatment-emergent adverse events (TEAEs): 419 (84.3%) patients on FIL+MTX and 203 (83.9%) patients on FIL monotherapy; serious TEAEs occurred in 45 (9.1%) and 33 (13.6%), respectively. Adverse event of special interest (AESI) rates remained low at week 156 (Table 1). Grade ≥3 toxicities in >1% of patients were decreased lymphocytes (4.2%/1%), decreased neutrophils (1.0/1.2%), increased fasting triglycerides (2.2/0%) and decreased fasting triglycerides (0/3.3%) for FIL+MTX/FIL monotherapy respectively. 5 deaths occurred (FIL+MTX: 2, FIL monotherapy: 3) none after week 132. Clinical efficacy was shown at week 156 in both FIL+MTX and FIL monotherapy groups, using observed cases as measured by ACR20 (87.2% and 89.7%)/ACR50 (72.4 and 63.0)/ACR70 (45.5 and 40.0) DAS28(CRP) ≤3.2 (69.0 and 64.7) and DAS28(CRP) Conclusion FIL was generally well tolerated; no new safety signals emerged. No safety differences observed in patients receiving FIL+MTX or FIL monotherapy. Efficacy was sustained up to week 156 in both treatment groups.