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Background/Aims In PREVENT (NCT02696031), secukinumab decreased sacroiliac joints (SIJ) bone marrow oedema (BMO) in patients with non-radiographic axial spondyloarthritis (nr-axSpA) through 52 weeks. We report radiographic progression and inflammation (BMO) assessed by X-ray and magnetic resonance imaging (MRI) of SIJ and spine over 2 years in PREVENT. Methods Patients (N = 555) were randomised (1:1:1) to secukinumab 150 mg, with loading dose (LD) or without (NL), or placebo. Switching to open-label secukinumab or standard of care (SoC) was permitted after Week (W) 20. By W52, all patients received open-label secukinumab or SoC. SIJ and spinal radiographs were collected at baseline and W104 and SIJ and spinal MR scans at baseline, W16, W52 and W104. Spinal radiographs were scored using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and SIJ radiographs using modified New York criteria (mNYC). SIJ and spinal BMO was assessed using Berlin Active Inflammatory Lesions Scoring and Berlin MRI scoring, respectively. Average scores of two blinded central readers were used. W104 reading data are presented as observed. Results Radiographs showed most patients (88% secukinumab, 86% placebo) had no SIJ progression (defined as change ≤ smallest detectable change [SDC, 0.46] in total mNYC score) by W104; no patient had an increase ≥2. At W104, screening radiographs of eligible patients were re-evaluated alongside post-baseline images; ∼25% of screening radiographs (68/277 secukinumab; 34/139 placebo) were re-evaluated as mNYC-positive by > 1 reader. Of these, 11/68 patients in the secukinumab (16.2%) and 5/34 in the placebo (14.7%) groups were evaluated as mNYC-negative at W104. Most patients who were mNYC-negative at screening remained mNYC-negative through W104 (202 secukinumab [96.7%]; 102 placebo [97.1%]). Almost all patients (98%) treated with secukinumab 150 mg (pooled LD and NL) showed no structural progression (change in total mSASSS ≤ SDC, [80% agreement level] of 0.76 over 2 years. At baseline, 62 patients (43 secukinumab, 19 placebo) presented with ≥1 syndesmophyte (≥1 vertebral unit scored by ≥ 1 reader). Of those 16 (9 secukinumab [20.9%]; 7 placebo [36.8%]) developed ≥1 new syndesmophyte by W104. Whilst of 354 patients (237 secukinumab, 117 placebo) without syndesmophytes at baseline, only 8 (4 secukinumab [1.7%]; 4 placebo [3.4%]) developed ≥1 new syndesmophyte by W104. Secukinumab reduced SIJ BMO score at W16 (-1.2) and W52 (-1.5) with sustained reduction through W104 (-1.7) in the overall population; greater reduction was observed in patients with baseline score >2 (W16, -4.0; W52, -4.7; W104, -5.4). Baseline spinal inflammation on MRI was low (mean Berlin score: 0.82, secukinumab; 1.07, placebo) with no meaningful change up to W104 (0.56, secukinumab). Conclusion Most patients showed no radiographic progression through 2 years. There was some discrepancy between SIJ eligibility and efficacy reads. Secukinumab reduced SIJ inflammation (BMO) on MRI in patients with active nr-axSpA. Disclosure H. Marzo-Ortega: Consultancies; H.M.O. has received consultancy fees from AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Takeda and UCB. Member of speakers’ bureau; H.M.O. has received speakers bureau fees from AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Takeda and UCB. Grants/research support; H.M.O. has received grant/research support from Janssen, Novartis and UCB. J. Braun: Consultancies; J.B. has received consultancy fees from AbbVie (Abbott), Amgen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Centocor, Chugai, Eli Lilly, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB. Member of speakers’ bureau; J.B. has received speakers bureau fees from AbbVie (Abbott), Amgen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Centocor, Chugai, Eli Lilly, Medac, MSD (Schering-Plough), Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB. Grants/research support; J.B. has received grant/research support from AbbVie (Abbott), Amgen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Centocor, Chugai, Eli Lilly, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB. R. Blanco: Member of speakers’ bureau; R.B. has received speakers bureau fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, MSD, Pfizer, Roche and UCB. Grants/research support; R.B. has received grant/research support from AbbVie, MSD and Roche. L.S. Gensler: Consultancies; L.S.G. has received consultancy fees from AbbVie, Eli Lilly, Gilead, Janssen, MoonLake, Novartis, Pfizer and UCB. Grants/research support; L.S.G. has received grant/research support from Janssen, Novartis and UCB. F. van den Bosch: Consultancies; F.v.d.B. has received consultancy fees from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer and UCB. Member of speakers’ bureau; F.v.d.B. has received speakers bureau fees from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer and UCB. Grants/research support; F.v.d.B. has received grant/research support from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer and UCB. S. Hall: Member of speakers’ bureau; S.H. has received speakers bureau fees from Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB; consultancy fees from Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB. Grants/research support; S.H. has received and grant/research support from AbbVie, Janssen, Merck and UCB. H. Kameda: Consultancies; H.K. has received consultancy fees from AbbVie, Eli Lilly, Gilead Sciences, Janssen, Novartis, Pfizer, Sanofi, Taisho and UCB. Member of speakers’ bureau; H.K. has received speakers bureau fees from AbbVie, Asahi-Kasei, AstraZeneca, Boehringer Ingelheim, BMS, Chugai, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Novartis and Pfizer. Grants/research support; H.K. has received grant/research support from AbbVie, Asahi-Kasei, Boehringer Ingelheim, Chugai, Eisai, Mitsubishi Tanabe and Taisho. D. Poddubnyy: Consultancies; D.P. has received consultancy fees from AbbVie, Biocad, BMS, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Samsung Bioepis and UCB. Member of speakers’ bureau; D.P. has received speakers bureau fees from AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer and UCB. Grants/research support; D.P. has received grant/research support from AbbVie, Eli Lilly, MSD, Novartis and Pfizer. M.G.H. van de Sande: Consultancies; M.G.H.v.d.S. has received consultancy fees from AbbVie, Eli Lilly, Novartis and UCB. Member of speakers’ bureau; M.G.H.v.d.S. has received speakers bureau fees from Novartis and UCB. Grants/research support; M.G.H.v.d.S. has received grant/research support from Eli Lilly, Janssen, Novartis and UCB. D. van der Heidje: Other; D.v.d.H. has worked as a paid instructor for AbbVie, Bayer, BMS, Cyxone, Eisai, Eli Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Novartis, Pfizer and UCB; and as a Director of Imaging Rheumatology at BV. T. Zhuang: Shareholder/stock ownership; T.Z. is a shareholder of Novartis. Other; T.Z. is an employee of Novartis. A. Stefanska: Shareholder/stock ownership; A.S. is a shareholder of Novartis. Other; A.S. is an employee of Novartis. A. Readie: Shareholder/stock ownership; A.R. is a shareholder of Novartis. Other; A.R. is an employee of Novartis. H. Richards: Shareholder/stock ownership; H.R. is a shareholder of Novartis. Other; H.R. is an employee of Novartis. A. Deodhar: Consultancies; A.D. has received consultancy fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, Novartis, Pfizer and UCB. Member of speakers’ bureau; A. D. has received speakers bureau fees from AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Pfizer and UCB. Grants/research support; A.D. has received grant/research support from AbbVie, Eli Lilly, GSK, Novartis, Pfizer and UCB.

Background/Aims Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to ≥ 1 biologic disease-modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study. We aimed to evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECT-PsA 2. Methods Pts were randomized to UPA 15 mg (UPA15), UPA 30 mg (UPA30), or placebo (PBO) for 24 wks; PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized for pts who received ≥1 dose of study drug using visit-based cut-off at wk 104. Results A total of 641 pts received ≥1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks. Similarly, mean change from baseline in HAQ-DI, patient’s assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 were consistent with that reported at wk 56. Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information; however, the patient had recently been diagnosed with ovarian cancer) and two with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion In PsA pts with prior inadequate response or intolerance to ≥ 1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to two years of treatment. No new safety signals were identified in this long-term extension. Disclosure P.J. Mease: Consultancies; Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB. Member of speakers’ bureau; Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB. Grants/research support; Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB. A. Setty: Shareholder/stock ownership; Financial Disclosures: Employee of AbbVie and may hold stock or options. K. Papp: Consultancies; Consultant of: AbbVie, Akros, Allergan, Almirall, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche. Member of speakers’ bureau; Speakers bureau: AbbVie, Akros, Allergan, Almirall, Amgen, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, Janssen, Kyowa. Grants/research support; Grant/research support from: AbbVie, Akros, Allergan, Almirall, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, G. F. Van den Bosch: Consultancies; Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB. Member of speakers’ bureau; Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB. S. Tsuji: Consultancies; Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, and UCB. Member of speakers’ bureau; Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, and UCB. Grants/research support; Grant/research support from: AbbVie, Eli Lilly, Janssen, Novartis, and UCB. M. Keiserman: Consultancies; Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB. Member of speakers’ bureau; Speakers bureau: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB. Grants/research support; Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB. X. Bu: Shareholder/stock ownership; Financial Disclosures: Employee of AbbVie and may hold stock or options. L. Chen: Shareholder/stock ownership; Financial Disclosures: Employee of AbbVie and may hold stock or options. R. Mccaskill: Shareholder/stock ownership; Financial Disclosures: Employee of AbbVie and may hold stock or options. E. Mcdearmon-Blondell: Shareholder/stock ownership; Financial Disclosures: Employee of AbbVie and may hold stock or options. P. Wung: Shareholder/stock ownership; Financial Disclosures: Employee of AbbVie and may hold stock or options. W. Tillett: Consultancies; Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, MSD, Novartis, Pfizer, and UCB. Member of speakers’ bureau; Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. Grants/research support; Grant/research support from: AbbVie, Celgene, Eli Lilly, and Janssen.

Objectives To assess whether two cluster analysis-based axial SpA (axSpA) endotypes (A for purely axial; B for both axial and peripheral) are stable over time and are associated with different long-term disease outcomes. Methods K-means cluster analysis was performed at each visit (until 5 years) on 584 patients from the DESIR cohort, who completed all planned visits, and validated in 232 consecutive axSpA patients from the BeGiant cohort. Cluster stability overtime was assessed by kappa statistics. A generalized linear mixed-effect analysis was applied to compare outcomes between clusters. Classification and regression tree (CART) analysis was performed to determine a decision rule able to assign a given patient to a definite cluster at onset. Results Both endotypes remained remarkably stable over time. In the DESIR cohort, patients in cluster B showed higher disease activity, worse functional outcome and higher need for anti-rheumatic drugs than patients in cluster A. CART analysis yielded three main clinical features (arthritis, enthesitis and dactylitis) that accurately determined cluster assignment. These results could be replicated in the Be-GIANT cohort. Conclusion Cluster-based axSpA endotypes were reproducible in two different cohorts, stable over time and associated with different long-term outcome. The axSpA endotype with additional peripheral disease manifestations is associated with more severe disease and requires more intensive drug therapy Clinical trial registration clinicaltrials.gov, https://clinicaltrials.gov, NCT01648907.

Objectives To delineate the impact of peripheral musculoskeletal manifestations on stratification of disease phenotype and outcome in new-onset spondyloarthritis (SpA), using a prospective observational nationwide inception cohort, the BelGian Inflammatory Arthritis and spoNdylitis cohorT (Be-Giant). Methods Newly diagnosed adult SpA patients, fulfilling the Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral SpA, were included in Be-Giant and prospectively followed every six months. Peripheral involvement (defined as arthritis, enthesitis and/or dactylitis) was determined in relation to clinically similar patient subsets at baseline and disease activity patterns during two-year follow-up, identified through K-means cluster analysis and latent class growth analysis. Results From November 2010 to March 2020, 367 patients were enrolled in Be-Giant, of whom 162 (44%) had peripheral manifestations. Two patient clusters [A, axial predominant (n = 248) and B, peripheral predominant (n = 119)] were identified at diagnosis. Longitudinal analysis (n = 115) revealed two trajectories of disease activity in each cluster: one with persistently high disease activity over time (‘High’), the other rapidly evolving to low disease activity (‘Low’). In cluster A patients, peripheral manifestations predisposed to the ‘High’ trajectory [odds ratio (OR) = 2.0, 95% CI: 1.3, 3.1, P = 0.001], despite more rapid initiation of biologics compared with patients without peripheral manifestations (hazard ratio (HR) = 2.1, 95% CI: 1.0, 4.4, P = 0.04 – Cox proportional-hazards model). Conclusion Peripheral musculoskeletal manifestations are major determinants of phenotypical diversity in new-onset SpA. Intriguingly, stratification of axial SpA according to concomitant peripheral involvement identified an endotype with an unfavorable outcome despite more prompt therapeutic intensification with biologics. These observations justify an endotype-tailored approach beyond current ASAS/EULAR management recommendations.

IL-23 is a key cytokine in the pathogenesis of spondyloarthritides, including PsA and axial spondyloarthritis, as well as related conditions, such as psoriasis and IBD. Genetic associations, animal models and translational studies in humans demonstrate the key role played by IL-23, especially when coupled with downstream overexpression of IL-17 via stimulation of T helper 17 (Th17) and other cells by IL-23. Whereas IL-23 inhibition has shown clear-cut benefit in psoriasis and peripheral manifestations of PsA, trials of IL-23 inhibitors have failed in the treatment of ankylosing spondylitis. More recently, exploratory data from PsA patients with axial symptoms suggests that improvement may occur, but needs confirmation in dedicated axial spondyloarthritis (axSpA) trials. Hypotheses for these apparently conflicting findings about IL-23 inhibition in various forms of spondylitis are discussed.

Objectives Treatment with golimumab monotherapy in early peripheral SpA (pSpA) results in higher rates of clinical remission compared with treatment in more longstanding disease. When reaching remission, treat-to-target recommendations suggest tapering of treatment. We therefore explored whether addition of MTX would permit discontinuation of golimumab in patients with pSpA in sustained clinical remission. Methods After a 2-year extension phase with golimumab treatment, patients with pSpA reaching clinical remission in the CRESPA trial were offered a tapering strategy leading to discontinuation of golimumab and replacement by MTX monotherapy. Patients were prospectively followed to assess the rate of sustained biologic-free clinical remission. In case of relapse of arthritis, enthesitis or dactylitis under MTX monotherapy, golimumab was restarted. Results Of the original 60 pSpA patients, 25 entered the step-down strategy. Currently, only 4 patients (16%) are still in sustained remission under MTX monotherapy. In 21 patients (84%), golimumab was reinstalled because of relapse of disease activity (n = 19) or development of adverse events related to MTX (n = 2). Restarting golimumab treatment promptly restored clinical remission in all patients within 12 weeks. Conclusion In patients with early pSpA achieving clinical remission after 2 years of golimumab treatment, step-down therapy to monotherapy with MTX led to high rates of clinical relapse. This underscores the overall weak efficacy of MTX in maintaining clinical remission in pSpA. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT01426815.

Background/Aims Tumor necrosis factor inhibitors (TNFis) are effective treatments for radiographic axial spondyloarthritis (r-axSpA), but may be less effective in patients (pts) without elevated C-reactive protein (CRP). This study evaluated the efficacy of ixekizumab (IXE), a high-affinity monoclonal antibody selectively targeting interleukin-17A, in pts with r-axSpA at 52 weeks (wks) with nonelevated (≤5mg/L) and elevated (>5mg/L) baseline (BL) CRP. Methods COAST-V (NCT02696785) and COAST-W (NCT02696798) were phase 3, multicenter, randomised, double-blind, PBO-controlled trials investigating efficacy of 80-mg IXE every 4 wks and every 2 wks in pts who met ASAS criteria for raxSpA, had radiographic sacroiliitis according to mNY criteria, and were biological diseasemodifying antirheumatic drug (bDMARDs)-naïve (COAST-V) or TNFiexperienced (COAST-W). Data from 157 COAST-V pts and 188 COAST-W pts treated with IXE from Wk0 to 52 were analyzed. Patients were stratified based on nonelevated (≤5mg/L) vs elevated (>5 mg/L) BL CRP. Additional analysis was done with BL CRP ≤10.0mg/L vs > 10.0mg/L. Efficacy was assessed by ASAS40, ≥50% improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50), and change in Short Form 36 physical component summary (SF36 PCS) score. Missing data were imputed by nonresponder imputation for binary measures and modified BL observation carried forward for continuous measure. Week 16 data are presented for comparison. Results Of pts treated with IXE through Wk52, 34.4% had CRP ≤5.0mg/L, 65.6% had CRP >5.0mg/L, 61.8% had CRP ≤10.0mg/L, and 38.2% had CRP >10.0mg/L at BL in COASTV and 33.0% had CRP ≤5.0mg/L, 67.0% had CRP >5.0mg/L, 55.9% had CRP ≤10.0mg/L, and 44.1% had CRP >10.0mg/L at BL in COAST-W.At Wk16, the proportion of pts achieving ASAS40 in COAST-V was numerically higher with IXE in the ≤5mg/L group and significantly higher with IXE in the >5mg/L group vs PBO, as previously shown, and was significantly higher with IXE in the ≤10mg/L and >10mg/L groups vs PBO. Results were similar in COAST-W and significant in the >5mg/L and ≤10mg/L groups vs PBO. At Wk52, greater than 45% of COAST-V pts and greater than 35% of COAST-W pts treated with IXE achieved an ASAS40 response, greater than 40% of COAST-V pts and greater than 25% of COAST-W patients treated with IXE achieved a BASDAI50 response, and change from baseline in SF-36 PCS score in patients treated with IXE was greater than 5 points in both studies regardless of the BL CRP cutoffs evaluated. Conclusion A higher proportion of ASAS40 responders was observed in IXE treated arms versus PBO among bDMARD-naïve and TNFi-experienced pts with r-axSpA when the CRP cutoff of 10mg/L was evaluated, and the responses were consistent through Wk52. Furthermore, similar proportions of pts achieved BASDAI50 and SF-36 responses within each patient population regardless of the BL CRP cutoff evaluated. Disclosure J.D. Reveille: None. P. Rahman: None. D.M. Sandoval Calderon: Shareholder/stock ownership; D. Sandoval Calderon is a shareholder and employee of Eli Lilly and Company. T. Muram: Shareholder/stock ownership; T. Muram is a shareholder and employee of Eli Lilly and Company. A. Kronbergs: Shareholder/stock ownership; A. Kronbergs is a shareholder and employee of Eli Lilly and Company. R. Bolce: Shareholder/stock ownership; R.Bolce is a shareholder and employee of Eli Lilly and Company. V. Geneus: Shareholder/stock ownership; V. Geneus is a shareholder and employee of Eli Lilly and Company. T. Hunter: Shareholder/stock ownership; T. Hunter is a shareholder and employee of Eli Lilly and Company. S. Liu-Leage: Shareholder/stock ownership; S.L. League is a shareholder and employee of Eli Lilly and Company. M. Rudwaleit: None. J.A. Maldonado-Cocco: None. F. van den Bosch: None.

Background/Aims Upadacitinib (UPA) is a selective JAK inhibitor licensed for moderate-severe rheumatoid arthritis (RA), under evaluation for treating psoriatic arthritis (PsA). We aim to assess the efficacy and safety of UPA versus placebo (PBO) in PsA patients with prior inadequate response or intolerance to ≥ 1 biologic disease-modifying anti-rheumatic drug (bDMARD). This research was previously presented at EULAR; published in Annals of Rheumatic Diseases. Methods In SELECT-PsA-2, patients were randomised 1:1:1 to once-daily UPA 15mg (UPA15), UPA 30mg (UPA30), or PBO. Patients were stratified by baseline DMARD use, number of prior failed bDMARDs, and extent of psoriasis. Primary endpoint: the proportion of patients achieving ACR20 response at Wk12. Multiplicity controlled secondary endpoints: change in HAQ-DI, FACIT-Fatigue (FACIT-F), SF-36 Physical Component Summary (PCS) at Wk12, static Investigator Global Assessment (sIGA) of Psoriasis of 0/1 and at least a 2-point improvement from baseline, PASI75, change in Self-Assessment of Psoriasis Symptoms (SAPS) at Wk16 and proportion of patients achieving MDA at Wk24. Additional secondary endpoints: ACR50 and ACR70 at Wk12, ACR20 at Wk2. Treatment-emergent adverse events (TEAEs) reported for patients receiving ≥1 dose of study drug. Results 641 patients were randomized and received study drug; 54.3% were female with mean age of 53.4 years and mean duration since PsA diagnosis of 10.1 years, 61%,18%, 13% of patients failed 1, 2, ≥3 bDMARD respectively. 543 (84.6%) patients completed Wk24 study drug. At Wk12, a significantly greater proportion of patients receiving UPA15 and UPA30 vs PBO achieved ACR20 (56.9% and 63.8% vs 24.1%; p < 0.0001 for both comparisons). Statistically significant improvements were observed in UPA15 and UPA30 arms vs PBO in all multiplicity controlled secondary endpoints, including ΔHAQ-DI (PBO, -0.10; UPA15, -0.30; UPA30, -0.41), ΔSF-36 PCS (PBO, 1.6; UPA15, 5.2; UPA30, 7.1), ΔFACIT-F (PBO, 1.3; UPA15, 5.0; UPA30, 6.1), and ΔSAPS (PBO, -1.5; UPA15, -24.4; UPA30, -29.7; p < .0001 for all endpoints). In addition, a greater proportion of patients achieved ACR50 and ACR70 at Wk12 with UPA vs PBO. Generally, TEAEs were reported at similar frequencies in the PBO and UPA15 arms and at a higher frequency in the UPA30 arm. Numerically higher rates of serious AEs were reported in the UPA arms. Herpes zoster was more frequent with UPA30. Three malignancies occurred in each UPA arm. One adjudicated non-fatal myocardial infarction and one adjudicated pulmonary embolism were reported with UPA15. Conclusion In this bDMARD-IR PsA population, UPA15 and UPA30 demonstrated significant improvements across PsA domains including improvements in joint and skin signs and symptoms vs PBO through Wk24, with improvement observed by Wk2. A greater percentage of patients treated with UPA achieved MDA and ACR50/70, stringent composite measures of disease control. No new safety signals were identified compared to those with UPA in RA. Disclosure M.C. Genovese: Consultancies; M.G. is a consultant for AbbVie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme. Grants/research support; M.G. has received grants/research support from AbbVie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme. A. Lertratanakul: Shareholder/stock ownership; A.L. is a stock/shareholder of AbbVie Inc. J. Anderson: Shareholder/stock ownership; J.A. may be a stock/ shareholder of AbbVie Inc. K. Papp: Consultancies; K.P. is a consultant for AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma, *. Member of speakers’ bureau; K.P. is a member of the speakers bureau for AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma *. Grants/research support; K.P. has received grants/research support from AbbVie, Amgen, Astellas, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Galderma *. Other; * & Genentech, GlaxoSmithKline,Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono,Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Takeda, UCB and Valeant. W. Tillett: Consultancies; W.T. is a consultant of AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc. & UCB. Member of speakers’ bureau; W.T. is a member of the speakers bureau for AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc. & UCB. Grants/research support; W.T. has received grants/research support from AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB. F. van den Bosch: Consultancies; F.vdB. is a consultant of AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB. Member of speakers’ bureau; F.vdB. is a member of the speakers bureau for AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB. S. Tsuji: Member of speakers’ bureau; S.T. is a member of the speakers bureau for AbbVie, Asahi Kasei, Chugai, Daiichi Sankyo, Eli Lilly, Eisai, Mitsubishi Tanabe, Celgene, and Novartis Pharma K.K. Grants/research support; S.T. has received grants/research support from Eli Lilly. E. Dokoupilova: Grants/research support; E.D. has received grants/research support from Eli Lilly, AbbVie, Novartis, MAURO KEISERMAN. M. Keiserman: Honoraria; M.K. has received honoraria from Pfizer, Amgen, AstraZeneca, Anthera Pharmaceuticals, Bristol-Myers Squibb, Biogen Idec Inc, Celltrion Inc., Eli Lilly, Human Genome Sciences, Novartis, Roche, Sanofi,. Member of speakers’ bureau; M.K. is a member of the speakers bureau for Pfizer, Abbott, Actelion, AstraZeneca, Amgen, Roche, Bristol Myers Squibb, and Janssen. X. Wang: Shareholder/stock ownership; X.W. may be a shareholder of AbbVie Inc. S. Zhong: Shareholder/stock ownership; S.Z. may be a stock/ shareholder of AbbVie Inc. P. Zueger: Shareholder/stock ownership; P.Z. may be a stock/shareholder of AbbVie Inc. A. Pangan: Shareholder/stock ownership; A.P. may be a stock/shareholder of AbbVie Inc. P. Mease: Consultancies; P.M. is a consultant of Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB. Member of speakers’ bureau; P.M. is a member of the speakers bureau for Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB. Grants/research support; P.M. has received grants/research support from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB.

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 Enthesitis can be a debilitating extra-articular spondyloarthritis manifestation that causes considerable pain and reduced quality of life. We evaluated the effect of secukinumab on axial and peripheral enthesitis in ankylosing spondylitis (AS) patients with baseline enthesitis (BLE) across all MASES sites (N = 13), axial MASES sites (N = 11; 13 MASES minus Achilles tendons [AT] [AxS]), peripheral sites (N = 6; AT + lateral condyles of humerus/femur [PS]) and the AT (N = 2) at Weeks 16 and 52. Methods This post-hoc analysis pooled data across four AS studies (MEASURE 1-4) from patients originally randomised to secukinumab 150 mg (approved AS dose), 300 mg (MEASURE 3 only) or placebo with BLE (MASES >0). Evaluations included mean change from baseline in MASES score, complete resolution (CR; MASES=0) and improvement from baseline in MASES score ≥5 counts. Mixed-effect model repeat measurement analysis was performed on change from baseline in MASES score and non-responder imputation for resolution of enthesitis at Week 16; data are reported as observed at Week 52. Results 355 (70.4%), 58 (76.3%) and 280 (72%) patients had BLE in the 150 mg, 300 mg and placebo groups, respectively. Baseline characteristics were comparable across groups. At Week 16, mean change from baseline for overall MASES and at AxS was greater for secukinumab 150 mg (−2.4, −2.3) and 300 mg (−2.9, −2.9) vs placebo (−1.9, −1.8; P < 0.05, P < 0.01). At Week 16, patients treated with secukinumab 150 mg (40.8%, 42.7%) and 300 mg (36.2%, 42.1%) vs placebo (28.9%, 30.1%) achieved CR of enthesitis at overall MASES and AxS. Secukinumab 150 mg and 300 mg were consistently associated with a higher mean change in MASES and CR of enthesitis at PS and AT vs placebo. More patients treated with secukinumab 150/300 mg vs placebo achieved a higher threshold of improvement (≥5 counts) in overall MASES at Week 16. Further improvements were observed for all endpoints at Week 52 (Table 1). Conclusion Secukinumab 150 mg and 300 mg were associated with a higher mean change in MASES and CR of enthesitis for overall MASES and at AxS vs placebo in AS patients at Week 16, which further improved through Week 52. Disclosures N. Barkham Grants/research support; Novartis, Eli Lilly, UCB, Celgene. G. Schett None. X. Baraliakos Consultancies; AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB Pharma, Galapagos. Member of speakers’ bureau; AbbVie, Chugai, Janssen, Novartis, Pfizer, UCB Pharma. Grants/research support; AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer, Roche, UCB. F. van den Bosch Consultancies; AbbVie, Bristol-Myers Squibb, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Bristol-Myers Squibb, Janssen, Lilly, Merck, Novartis, Pfizer, UCB. A. Deodhar Consultancies; AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, UCB. L.S. Gensler Consultancies; Novartis, Lilly, Janssen. Grants/research support; AbbVie, Amgen, UCB Pharma. M. Ǿstergaard Consultancies; AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, UCB. Member of speakers’ bureau; AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, UCB. Grants/research support; AbbVie, Celgene, Centocor, Merck, Novartis. S. Agawane Other; Employee of: Novartis. A. Das Gupta Other; Employee of: Novartis. S. Mpofu Other; Employee of: Novartis. T. Fox Other; Employee of: Novartis. A. Winseck Other; Employee of: Novartis. A. Shete Shareholder/stock ownership; Novartis. Other; Employee of: Novartis. B. Porter Shareholder/stock ownership; Novartis. Other; Employee of: Novartis.

Objective The aim was to assess the long-term safety and efficacy of certolizumab pegol over 4 years of continuous treatment in patients with axial spondyloarthritis (axSpA), including both AS and non-radiographic (nr-) axSpA. Methods RAPID-axSpA was a phase 3 randomized trial, double blind and placebo controlled to week 24, dose blind to week 48 and open label to week 204. Patients had a clinical diagnosis of axSpA, meeting Assessment of SpondyloArthritis international Society (ASAS) criteria, and had active disease. The assessed outcomes included ASAS20, ASAS40, AS DAS (ASDAS), BASDAI, BASFI and BASMI scores, along with selected measures of remission. Further patient-reported outcomes, peripheral arthritis, enthesitis, uveitis and quality-of-life measures are also reported. Results Two hundred and eighteen of 325 patients randomized (AS: 121; nr-axSpA: 97) received certolizumab pegol from week 0. Of these, 65% remained in the study at week 204 (AS: 67%; nr-axSpA: 63%). Across all outcomes, for AS and nr-axSpA, sustained improvements were observed to week 204 [week 204 overall axSpA: ASAS20: 54.1% (non-responder imputation); 83.7% (observed case, OC); ASAS40: 44.0% (non-responder imputation); 68.1% (OC); ASDAS inactive disease: 32.1% (last observation carried forward); 31.4% (OC)]. In the safety set (n = 315), there were 292.8 adverse events and 10.4 serious adverse events per 100 patient-years. No deaths were reported. Conclusion In the first study to evaluate the efficacy of an anti-TNF across both axSpA subpopulations, improvements in clinical and patient-reported outcomes at 24 and 96 weeks were sustained through 4 years of treatment, with no new safety signals. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT01087762.

Background: Baricitinib, an oral JAK1/JAK2 inhibitor, improves disease activity with an acceptable safety profile in patients with active rheumatoid arthritis (RA). We report efficacy and safety data for baricitinib as monotherapy or in combination with methotrexate (MTX), compared with MTX, in[for full text, please go to the a.m. URL]

To assess the baseline condition of the SI joints (SIJs) in healthy individuals without symptoms of back pain and to study the effect of mechanical stress caused by intense physical training on MRI of the SIJs. Twenty-two military recruits underwent an MRI of the SIJs before and after 6 weeks of intense standardized physical training. Bone marrow oedema and structural lesions were scored based on the Spondyloarthritis Research Consortium of Canada (SPARCC) method, by three trained readers blinded for time sequence and clinical findings. Additionally, fulfilment of the Assessment of SpondyloArthritis international Society (ASAS) definition of a positive MRI was evaluated. At baseline, 9/22 recruits (40.9%) already presented a SPARCC score a (c) 3/41; this number increased to 11/22 (50.0%) at week 6 (P = 0.625). In these patients, the mean (SD) SPARCC score was 2.4 (0.4) at baseline, compared to 3.7 (1.3) at week 6. Overall, the mean (SD) change in SPARCC score over time in all 22 patients was 0.9 (0.6) (P = 0.109). A positive MRI according to the ASAS definition was present in 5/22 recruits (22.7%) at baseline, which increased to 8/22 (36.4%) at follow-up (P = 0.375). Structural lesions were present in 6/22 subjects (27.3%), both at baseline and after 6 weeks of training. A substantial proportion of healthy active individuals without any symptoms of back pain displayed bone marrow oedema lesions on MRI at baseline. However, MRI lesions did not increase significantly after 6 weeks of intensive physical training. Our study underscores the necessity to interpret MRI findings of the SIJs in the appropriate clinical context, even in a young active population. Ghent University Hospital; Het Fonds voor Wetenschappelijk Reuma Onderzoek