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Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumoral overproduction of FGF-23. Due to local recurrence, we describe the long-term efficacy and safety profile of burosumab, an anti-FGF-23 monoclonal antibody, in a TIO patient after three unsuccessfully surgical attempts.TIO is a rare paraneoplastic syndrome caused by tumoral overproduction of fibroblast growth factor 23 (FGF23), resulting in hyperphospaturia, hypophosphatemia, and osteomalacia. Surgery is the only definitive treatment, but tumor can locally recur, even after years from primary surgery. Furthermore, some tumors cannot be removed by surgery due to their location.We describe the case of a 54-year-old woman affected by recurrent TIO who, after three unsuccessful surgical attempts of tumor removal, was treated with burosumab, an anti-FGF-23 monoclonal antibody.The patient was referred to our Bone Unit after experiencing several fractures in different sites, both traumatic and non-traumatic. At the time of first evaluation, at the age of 46, serum-phosphate (SP) was 1.2 mg/dL (reference range (RR) 2.5-4.5), 24-h urinary phosphate was 842 mg (RR 400-1000), and intact-FGF-23 was 117 pg/mL (RR 25-45). Imaging showed a metabolic pre-sacral lesion that firstly underwent to exploratory laparotomy. Then, patient underwent to surgical excision of tumor. After 18 months of well-being, tumor relapsed and even the subsequent surgery was not able to completely remove it. Since 2015, patient was maintained in phosphorus supplements and 1,25(OH)To our knowledge, this is the first European patient affected by TIO treated with burosumab for more than 2 years. Burosumab is a promising therapy in the medical treatment of TIO refractory or not eligible for definitive surgery, with good efficacy and safety profile.

BackgroundThe preferential Janus kinase-1 inhibitor FIL is approved for treatment of moderate to severe active RA in Europe and Japan.ObjectivesEfficacy and safety of FIL were assessed in patients (pts) with IR to bDMARDs in a LTE trial (NCT03025308) enrolled from a Phase 3 PS (NCT02873936).1MethodsbDMARD-IR pts received FIL 200 mg (FIL200), FIL 100 mg (FIL100), or placebo (PBO), all with stable conventional synthetic (cs)DMARDs up to 24 weeks (W). At W14 of the PS, pts with IR to FIL or PBO (ResultsThe PS included 147, 153, and 148 pts on FIL200, FIL100, and PBO. Pts continuing on LTE FIL200 and FIL100 at data cutoff: 80/121 (66%) and 76/110 (69%) from PS FIL200 and FIL100; 35/47 (75%) and 32/46 (70%) from PS PBO, and 13/23 (57%) and 13/22 (59%) from PS SOC. LTE baseline (BL) characteristics were similar in FIL200 and FIL100 pts. During LTE, PS FIL ACR20/50/70 response rates decreased modestly by W48 (Figure 1). Among PS PBO pts, response rates were lower at LTE BL, reaching similar levels to PS FIL pts by W48; rates increased to W48 in PS SOC pts on either FIL dose but not to levels of other groups. Percentages of pts attaining DAS28(CRP) ≤3.2, DAS28(CRP) Table 1.EAIRs of TEAEs in LTE, as of June 1, 2020EAIR (95% CI)FIL200+csD → FIL200+csD n=121PYE 228.4PBO+csD → FIL200+csD n=47PYE 98.1SOC+csD → FIL200+csD n=23PYE 42.1FIL100+csD → FIL100+csD n=110PYE 223.3PBO+csD → FIL100+csD n=46PYE 91.1SOC+csD → FIL100+csD n=22PYE 38.2TEAE46.9 (38.8, 56.6)38.7 (28.2, 53.2)52.2 (34.4, 79.3)40.3 (32.8, 49.5)40.6 (29.4, 56.1)49.8 (31.8, 78.0)TEAE Grade ≥310.5 (7.0, 15.7)10.2 (5.5, 18.9)19.0 (9.5, 38.0)10.3 (6.8, 15.5)13.2 (7.5, 23.2)18.3 (8.7, 38.5)TE serious AE12.3 (8.5, 17.8)12.2 (6.9, 21.5)21.4 (11.1, 41.1)8.1 (5.1, 12.8)13.2 (7.5, 23.2)21.0 (10.5, 41.9)Death1.3 (0.4, 4.1)1.0 (0, 5.7)0 (0, 8.8)0.4 (0.1, 3.2)0 (0, 4.0)0 (0, 9.7)TE infections34.2 (27.4, 42.6)22.4 (14.8, 34.1)35.6 (21.5, 59.1)22.4 (17.0, 29.5)26.3 (17.7, 39.3)39.3 (23.7, 65.2)TE serious infections3.5 (1.8, 7.0)2.0 (0.5, 8.2)7.1 (2.3, 22.1)0.9 (0.2, 3.6)2.2 (0.5, 8.8)7.9 (2.5, 24.4)Opportunistic infections0 (0, 1.6)0 (0, 3.8)0 (0, 8.8)0 (0, 1.7)0 (0, 4.0)0 (0, 9.7)TE herpes zoster2.2 (0.7, 5.1)1.0 (0.1, 7.2)0 (0, 8.8)0 (0, 1.7)2.2 (0.5, 8.8)2.6 (0.1, 14.6)TE MACE (adjudicated)1.3 (0.4, 4.1)1.0 (0.1, 7.2)0 (0, 8.8)0.9 (0.2, 3.6)1.1 (0.2, 7.8)0 (0, 9.7)TE DVT/PE (adjudicated)0.9 (0.2, 3.5)0 (0, 3.8)2.4 (0.1, 13.2)0.4 (0.1, 3.2)0 (0, 4.0)0 (0, 9.7)Malignancies (excluding NMSC)1.3 (0.4, 4.1)3.1 (1.0, 9.5)4.7 (0.6, 17.2)1.8 (0.7, 4.8)3.3 (1.1, 10.2)0 (0, 9.7)NMSC0 (0, 1.6)0 (0, 3.8)4.7 (0.6, 17.2)0 (0, 1.7)0 (0, 4.0)0 (0, 9.7)DVT, deep vein thrombosis; MACE, major adverse cardiovascular event; NMSC, nonmelanoma skin cancer; PE, pulmonary embolism; TE, treatment-emergentConclusionEfficacy was mostly maintained in PS FIL pts up to W48. Response among PS PBO and SOC pts increased from BL to W48, but response in PS SOC pts continued to be lower than in other groups; these pts may represent a refractory population. FIL safety was largely consistent between PS and LTE.References[1]Genovese MC et al. JAMA 2019;322:315–25.AcknowledgementsThis study was funded by Gilead Sciences, Inc., Foster City, CA. Medical writing support was provided by Claudine Bitel, PhD, of AlphaScientia, LLC, San Francisco, CA; and funded by Gilead Sciences, Inc., Foster City, CA.Disclosure of InterestsMaya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Galapagos, Gilead, and Pfizer, Grant/research support from: Gilead and Pfizer, Tsutomu Takeuchi Speakers bureau: AbbVie, AYUMI, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Eli Lilly Japan, Gilead Sciences, 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, Vijay Rajendran Shareholder of: Galapagos, Employee of: Galapagos, Jacques-Eric Gottenberg Speakers bureau: AbbVie, Eli Lilly and Co., Galapagos, 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, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., YingMeei Tan Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Qi Gong Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Katrien Van Beneden Shareholder of: Galapagos, Employee of: Galapagos, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, and UCB, Consultant of: AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Lilly, Fresenius-Kabi, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB

BackgroundRheumatoid arthritis (RA) is characterized by chronic inflammatory synovitis and progressive disability. Nowadays the natural history and the prognosis of the disease has deeply changed thanks to the availability of conventional and targeted disease modifying anti-rheumatic drugs (DMARDs). Nevertheless, clinical response to treatment is highly variable and a considerable proportion of patients do not - or only partially - respond to the treatment. The stratification of patients through the identification of biological predictors of good clinical response to treatment could allow the selection of the best therapeutic strategy for each patient. Recently, precision medicine in rheumatology could rely on the development of new transcriptomics techniques, such as RNA sequencing (RNAseq), that permit to explore complex cellular and molecular networks associated with pathophysiological aspects.ObjectivesTo characterize the transcriptomic profiles (RNAseq) of whole-blood samples of moderate to severe RA patients to predict the clinical response to tofacitinib.MethodsWe selected patients with active RA, candidate to receive tofacitinib after failure of a previous therapy with conventional or biologic DMARDs. RNAseq profiling on whole-blood samples (PAX gene tubes) was performed at baseline and after 24 weeks of treatment with tofacitinib. Treatment response was evaluated at week 24 by CDAI EULAR response criteria as drug responder (major or moderate response) or non-responder (minor or no response). Differential expression of gene ontology (GO) biological processes (BP) pathways was analyzed to identify the response-associated pathways. Machine learning models were built by different data mining algorithm to predict response to tofacitinib.ResultsThe study population included 33 patients, of whom 7 discontinued prematurely the treatment (5 because of adverse events and 2 because of inefficacy) and 2 were lost to follow-up. At week 24, 10 patients (38.5%) had major, 4 (15.4%) moderate, 6 (23.1%) minor, and 6 (23.1%) no clinical response to tofacitinib. No significant difference was observed between responders and non-responders in terms of baseline characteristics (age, sex, rheumatoid factor and anti–cyclic citrullinated peptide [ACPA] positivity, DMARDs and prednisone exposure, Table 1). Overall, 307 out of 2137 coding transcripts and 85 GO BP pathways were differentially expressed after treatment in responders vs non-responders (Figure 1). In detail, an up-regulation of JAK-dependent pathways, including cation transport, metabolism of membrane lipids, calcium-mediated signaling, and osteoblast proliferation was observed in responders. Conversely, in non-responders, processes related to B cell activation, proliferation, and signaling along with mRNA epigenetic modifications were increased. After extensive internal validation (50 runs of 80:20 hold-out sampling) with univariate selection of GO terms, the accuracy of Support vector Machine (SVM) learning models to predict the correct clinical response was equal to 88.3% (AUROC = 0.940).Table 1.Demographic and baseline clinical characteristics of the study population*Non responders(n = 12)Responders(n = 14)Female, n (%)11 (91.7%)11 (78.6%)Age, years (±SD)52.6±11.254.3±10.5Rheumatoid factor, n (%)7 (58.3%)7 (50%)ACPA, n (%)9 (75%)8 (57.1%)Concomitant csDMARDs, n (%)5 (41.7%)8 (57.1%)bsDMARDs naïve, n (%)12 (100%)11 (78.6%)Prednisone ≥ 5mg/day, n (%)4 (33.3%)6 (42.8%)* There were no significant differences, determined by Fisher’s exact test for categorical variablesFigure 1.Heatmap representation of selected GO BP pathways in responders/non-responders.ConclusionMachine learning models based on transcriptomic functional pathways can accurately predict response to tofacitinib. Our study could contribute to improve the treatment customization and the optimization of RA treatment strategy toward a personalized approach. Furthermore, these findings may help to understand the mechanisms underlying the clinical response to JAK inhibitors.Disclosure of InterestsNone declared.

BackgroundBaricitinib (BARI), an oral selective Janus kinase 1/2 inhibitor, has demonstrated efficacy in patients (pts) with rheumatoid arthritis (RA) for up to 3 years (yrs) in a long-term extension (LTE) study RA-BEYOND.1ObjectivesDisclose efficacy of BARI in csDMARD-IR pts in the completed LTE study (up to 7 yrs).MethodsIn RA-BUILD, csDMARD-IR pts were randomized 1:1:1 to BARI 4 mg, 2 mg, or placebo (PBO). Completers to week (wk) 24 could enter the LTE and received BARI 4 or 2 mg. In RA-BEAM, MTX-IR pts were randomized 1:1:1 to BARI 4 mg, adalimumab (ADA) 40 mg, or PBO. Completers to wk 52 received BARI 4 mg in the LTE. Pts with no response could be rescued after wk 16 in both studies. Data were analysed by treatment assigned at baseline in originating studies as observed up to time of stepdown (if applicable), study discontinuation or completion, whichever occurred earlier. Efficacy response rates (RR) were assessed as proportions of pts with observed data up to yr 7 (wk 364) for low-disease activity (LDA) (SDAI ≤ 11, DAS28-hsCRP ≤ 3.2, CDAI ≤ 10), remission (REM) (SDAI ≤ 3.3, DAS28-hsCRP < 2.6, CDAI ≤ 2.8, Boolean), and physical function (HAQ-DI ≤ 0.5). No formal statistical comparisons were conducted.ResultsApproximately 56%/25% of pts in BARI 4 mg, 80%/31% in BARI 2 mg, and 60%/25% in PBO from RA-BUILD remained active at yr 3/7; 59%/17% of pts in ADA, 54%/16% in BARI 4 mg, and 67%/14% in PBO from RA-BEAM remained active at year 3/7. SDAI and CDAI had comparable RR for LDA and REM (Table 1). DAS-28CRP LDA RR were similar to SDAI and CDAI, while REM RR were about twice those of SDAI and CDAI (Table 1). HAQ-DI ≤ 0.5 RR was achieved by 25-30% of BARI-treated pts from both trials and maintained to the end of LTE.Table 1.Efficacy outcomes in RA-BEYONDTimeaN/n (%)LDAREMHAQ-DI ≤0.5SDAICDAIDAS-28 CRPSDAICDAIDAS-28 CRPBooleanRA-BEYOND entryBARI 2 mg (BUILD)197/109197/103200/108197/38 (19.3)197/35 (17.8)200/72 (36.0)200/29 (14.5)200/50 (25.0)(55.3)(52.3)(54.0)BARI 4 mg (BUILD)188/113191/116189/112188/33191/35 (18.3)189/75 (39.7)189/26 (13.8)193/44 (22.8)(60.1)(60.7)(59.3)(17.6)BARI 4 mg (BEAM)412/288414/290412/280412/112414/108412/199412/78 (18.9)414/133 (27.3)(69.9)(70.0)(68.0)(27.2)(26.1)(48.3)Yr 3BARI 2 mg (BUILD)156/120158/116156/112156/41 (26.3)158/44 (27.8)156/81 (51.9)156/34 (21.8)159/38 (23.9)(76.9)(73.4)(71.8)BARI 4 mg (BUILD)107/76107/76107/74107/24107/26 (24.3)107/56 (52.3)107/17 (15.9)108/26 (24.1)(71.0)(71.0)(69.2)(22.4)BARI 4 mg (BEAM)222/166224/166222/164222/72224/71 (31.7)222/119222/48224/54 (24.1)(74.8)(74.1)(73.9)(32.4)(53.6)(21.6)Yr 7BARI 2 mg (BUILD)61/5061/4961/5161/17 (27.9)61/18 (29.5)61/40 (65.6)61/12 (19.7)62/16 (25.8)(82.0)(80.3)(83.6)BARI 4 mg (BUILD)45/3748/3745/3445/13 (28.9)48/16 (33.3)45/25 (55.6)45/8 (17.8)48/14 (29.2)(82.2)(77.1)(75.6)BARI 4 mg (BEAM)60/5364/5760/53 (88.3)60/18 (30.0)64/22 (34.4)60/38 (63.3)60/13 (21.7)64/14 (21.9)(88.3)(89.1)N: Number of pts with observed data; n: Number of pts with response. aTime from randomization in originating studies. Entry to RA-BEYOND=wk 24 and wk 52; Yr 3=wk 156 and wk 160; and Yr 7=wk 360 and wk 364 of RA-BUILD and RA-BEAM, respectively.ConclusionIn observed data, BARI demonstrated maintained efficacy in treatment and maintenance of physical function of a csDMARDs-IR RA pt population up to 7 yrs.References[1]Smolen JS, et al. Rheumatology (Oxford). 2021; 60(5):2256-66.Disclosure of InterestsRoberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Eli Lilly and Company, Galapagos, Pfizer, Fresenius-Kabi, MSD, UCB, Roche,Janssen, Novartis, Sandoz, Consultant of: Abbvie, Amgen, BMS, Celltrion, Eli Lilly and Company, Galapagos, Pfizer, MSD, UCB, Janssen, Novartis, Sandoz, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: Abbvie, Amgen, Eli Lilly and Company, Novartis, Roche, SoBi, Sanofi, Raimón Sanmartí Speakers bureau: Eli Lilly and Company, Grant/research support from: Eli Lilly and Company, Tsutomu Takeuchi Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan K.K.; Gilead Sciences, Inc. Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Co.; Novartis Pharma Co.; Pfizer Japan Inc.; Sanofi K.K.; UCB Japan Co., Ltd., Consultant of: AbbVie Japan GK, Astellas Pharma, Inc.; Chugai Pharmaceutical Co, Ltd.; Eli Lilly Japan K.K.; Eisai Co., Ltd.; Gilead Sciences, Inc.; Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Corp., Pfizer Japan Inc., Grant/research support from: AbbVie Japan GK, Asahikasei Pharma Corp., Chugai Pharmaceutical Co, Ltd., DNA Chip Research Inc.; Eisai Co., Ltd., Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Corp., UCB Japan Co., Ltd., Daojun Mo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Ewa Haladyj Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Liliana Zaremba-Pechmann: None declared, Peter C. Taylor Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Inc, Roche, and Sanofi, Grant/research support from: Celgene, and Galapagos

BackgroundFIL is a Janus kinase (JAK) 1 preferential inhibitor approved for the treatment (tx) of moderate to severe RA. Weight gain has been reported with other JAK inhibitors1–3; it is important to describe the effect of FIL on BW/BMI for physicians to correctly inform and appropriately treat patients.ObjectivesOur primary aim was to assess the effect of FIL on BW/BMI using data from the FINCH 1–3 studies. Secondary aims were to assess the efficacy and safety of FIL according to baseline BMI.MethodsFINCH 1–3 (NCT02889796, NCT02873936, NCT02886728) were phase 3, randomised, double-blind, active/placebo (PBO)-controlled studies of FIL 100/200 mg (FIL100/FIL200) ± methotrexate (MTX) in patients with active RA who had an inadequate response to MTX (FINCH 1) or biologic DMARD (FINCH 2), or were MTX naïve (FINCH 3). We assessed changes from baseline (CFB) in BW and BMI by tx group and baseline BMI, and the efficacy and safety of FIL by baseline BMI (2). Efficacy measures included American College of Rheumatology (ACR)20/50/70 response, Disease Activity Score 28 with C-reactive protein (DAS28-CRP) and health assessment questionnaire disability index (HAQ-DI). Safety data were from 7 RA clinical trials (FINCH 1–4, DARWIN 1–3)4.ResultsIn FINCH 1–3, baseline disease characteristics such as HAQ-DI, DAS28-CRP and clinical disease activity index were similar across BMI subgroups for each tx group. There were no clinically relevant CFB in median BW or BMI in any tx group or differences between tx groups. Mean CFB in BMI (kg/m2) were 0.4 with FIL200 and FIL100 and 0.3 with adalimumab (ADA) at Week 52 in FINCH 1; 0.2, 0.6 and −0.1 with FIL200, FIL100 and PBO, respectively, at Week 24 in FINCH 2; and 0.5, 0.6, 1.1 and 0.3 with FIL200+MTX, FIL100+MTX, FIL200 and MTX, respectively, at Week 52 in FINCH 3.CFB in BMI did not appear dependent on baseline BMI. FIL200±MTX was efficacious vs controls regardless of baseline BMI for most measures at each timepoint. In FINCH 1, in the 2 BMI subgroups, DAS28-CRP 2 BMI subgroups; serious infection rate was numerically higher with FIL100 in the 2 subgroup vs other BMI subgroups.Table 1.Exposure-adjusted incidence rate (95% CI) of AEs per 100 PYE by baseline BMIFIL dose (mg)BMI (kg/m2)25–≥30PYE 3062.8PYE 2640.1PYE 2382.2TEAEs20034.5 (32.0, 37.1)35.7 (33.0, 38.6)36.6 (33.7, 39.8)10044.3 (40.4, 48.6)43.0 (38.9, 47.5)45.3 (41.1, 50.0)Serious TEAEs2005.3 (4.4, 6.4)5.8 (4.8, 7.1)7.1 (5.8, 8.5)1007.6 (6.0, 9.4)6.5 (5.0, 8.4)8.1 (6.4, 10.2)Deaths2000.3 (0.2, 0.7)0.5 (0.3, 1.0)0.5 (0.2, 1.0)1000.4 (0.1, 1.0)0.3 (0.1, 1.0)0.2 (0.1, 0.9)Venous thrombotic and embolic events2000.1 (0.0, 0.4)0.1 (0.0, 0.5)0.5 (0.2, 1.0)1000.1 (0.0, 0.7)0.1 (0.0, 0.8)0.2 (0.1, 0.9)Major adverse cardiovascular events2000.3 (0.2, 0.7)0.3 (0.1, 0.7)0.5 (0.2, 1.0)1000.6 (0.3, 1.3)0.3 (0.1, 1.0)0.6 (0.2, 1.4)Serious infections2001.1 (0.7, 1.7)1.7 (1.2, 2.5)1.8 (1.2, 2.6)1002.6 (1.8, 3.9)1.2 (0.7, 2.2)2.2 (1.4, 3.4)Herpes zoster2001.6 (1.1, 2.2)1.4 (1.0, 2.1)1.8 (1.2, 2.6)1001.0 (0.5, 1.8)1.2 (0.7, 2.2)1.0 (0.5, 2.0)Malignancy excluding nonmelanoma skin cancer2000.5 (0.3, 1.0)0.7 (0.4, 1.3)0.5 (0.3, 1.1)1000.6 (0.3, 1.3)0.4 (0.2, 1.2)0.8 (0.4, 1.7)BMI, body mass index; FIL, filgotinib; PYE, patient years of exposure; (TE)AE, (treatment-emergent) adverse eventConclusionFIL did not substantially affect CFB in BW or BMI. FIL200±MTX was generally more efficacious vs controls regardless of baseline BMI, and the rate of TEAEs was similar across baseline BMI subgroups.References[1]Tofacitinib SmPC[2]Baracitinib SmPC[3]Upadacitinib SmPC[4]Winthrop K, et al. ACR 2021. Abstract 1698AcknowledgementsThe FINCH studies were funded by Gilead Sciences (Foster City, CA, United States).We thank the physicians and patients who participated in the studies.Medical writing support was provided by Debbie Sherwood, BSc (Aspire Scientific Ltd, Bollington, UK) and funded by Galapagos NV (Mechelen, Belgium).Disclosure of InterestsAlejandro Balsa Speakers bureau: AbbVie, Galapagos, Gilead, Lilly, Nordic, Pfizer, Sandoz, and UCB, Consultant of: AbbVie, Galapagos, Lilly, Nordic, Pfizer, and UCB, Grant/research support from: AbbVie, Pfizer, UCB, Siegfried Wassenberg Speakers bureau: AbbVie, MSD, Pfizer, and Sanofi, Consultant of: AbbVie, Gilead, Lilly, Nichi-Iko, Pfizer, and UCB, Grant/research support from: Pfizer, Anne Tournadre Speakers bureau: Fresenius-Kabi and Sanofi, Paid instructor for: Fresenius-Kabi, Consultant of: AbbVie, Fresenius-Kabi, Lilly, Novartis, and Sanofi, Grant/research support from: Novartis, Pfizer, and UCB, Hans-Dieter Orzechowski Employee of: Galapagos, Katrien Van Beneden Shareholder of: Galapagos, Employee of: Galapagos, Vijay Rajendran Employee of: Galapagos, Udo Lendl Employee of: Galapagos, Pieter-Jan Stiers Shareholder of: Galapagos, Employee of: Galapagos, Chris Watson Shareholder of: Galapagos, Employee of: Galapagos, Roberto Caporali Speakers bureau: AbbVie, Accord, BMS, Celltrion, Fresenius-Kabi, Galapagos, Lilly, MSD, Novartis, Pfizer, Sandoz, and UCB, Consultant of: AbbVie, Accord, BMS, Celltrion, Fresenius-Kabi, Galapagos, Lilly, MSD, Novartis, Pfizer, Sandoz, and UCB, Patrick Verschueren Speakers bureau: Eli Lilly, Galapagos, MSD, and Roularta, Consultant of: AbbVie, BMS, Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Pfizer, Sidekick Health, and UCB, Grant/research support from: Pfizer Chair Management of Early Rheumatoid Arthritis at KU Leuven Belgium.

BackgroundShared decision making, a cornerstone of RA management1, allows physicians and their patients to make informed decisions about their treatment goals and choice of care. As new treatments become available, it is important to understand rheumatologists’ reasons for choosing JAKi.ObjectivesThis survey evaluated rheumatologists’ clinical and patient centric reasons for choosing JAKi, in addition to exploring alignment between rheumatologists and RA patients in terms of treatment choice and satisfaction.MethodsThe Adelphi RA Disease Specific Programme™2 is a large, multinational, point-in-time survey conducted amongst rheumatologists and their consulting patients with RA in Europe (Belgium, France, Germany, Italy, Spain, UK) between January and October 2020. Physicians completed record forms for up to 10 consecutive RA patients, collecting demographic, clinical and treatment data, and reasons for current treatment choice. Patients were invited to complete a patient questionnaire to assess their satisfaction with ongoing treatment (5-point scale), and perceptions of shared decision making for the current treatment.Results316 rheumatologists provided data for 3121 patients, of whom 1130 (36.2%) completed patient reported questionnaires. Overall, 67% were female, mean age was 53 years (SD 14), 23% had moderate-high disease activity score (DAS28: >3.2). 68% of patients were currently receiving either a biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD; defined here as advanced therapy, AT), 72% were on first line AT. Overall, physicians and their patients were aligned that a conversation took place about a treatment decision (n=855, 79% net alignment), and this was a shared treatment decision (n=814, 75% net alignment). 15% of patients not taking an AT were reported to have a clinical condition warranting one; reasons for not taking AT included patients’ concerns about infection (24%), conventional synthetic DMARDs were tolerable and safe in the patient (18%), and patient dislike of infusions/injections (17%). Of 2143 patients receiving AT, 19% were prescribed JAKi; 57% as monotherapy, 43% as combination therapy. For physician stated reasons for choice of JAKi, factors were driven by both perceptions of clinical efficacy and onset of action, as well as factors relating to patient acceptability such as method of delivery and ease of use (Table 1). With respect to JAKi treatment (n=135 patient-physician pairs), 62% of physicians and their patients were aligned on satisfaction, however 30% of patients reported less satisfaction than their consulting physician (Figure 1).Table 1.Physician stated clinical and patient centric reasons for prescribing a JAKi in their patients with RA (data are percentage of patients; n=397)Reasons for prescribing JAKiPatients (%)Top 5 clinical reasonsStrong overall efficacy74Fast onset of action49Inhibition of disease progression42Strong efficacy as monotherapy39Achievement of clinical remission37Top 5 patient centric reasonsAcceptability of method of delivery for the patient39Enabling patient to perform everyday tasks/activities36Ease of product use (for the patient)33Improvement or maintenance of quality of life30Improving patient’s mood/state of mind14ConclusionCommunicating the choice of pharmacological therapy to patients with RA has become increasingly complex for physicians with expansion of approved treatments. In this subgroup of patients on JAKi, the drug attributes considered as reasons for prescribing were driven by clinical factors as well as by patient centric attributes. Although communications between patients and physicians were largely aligned, better understanding of patient expectations might serve to improve messaging about treatment options and resulting satisfaction.References[1]Smolen JS et al. Ann Rheum Dis 2017;76.[2]Anderson P et al. Curr Med Res Opin 2008;24(11):3063–72.AcknowledgementsThe study was funded by Galapagos NV (Mechelen, Belgium). We thank the physicians and patients who participated in this survey. Medical writing support was provided by Gary Sidgwick, PhD (Adelphi Real World, Bollington, UK) and publications management was provided by Aspire Scientific Ltd, (Bollington, UK), funded by Galapagos NV.Disclosure of InterestsPeter C. Taylor Consultant of: AbbVie, Biogen, Bristol Myers Squibb, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Celgene and Galapagos, Bruno Fautrel Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, Sobi, and UCB, Grant/research support from: AbbVie, Lilly, MSD, and Pfizer, Yves Piette Consultant of: AbbVie, Galapagos, Grünenthal, Novartis, Janssen, and Sandoz, Susana Romero-Yuste Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Grunenthal, Janssen, Kern Pharma, Lilly, Roche, Sandoz, Sanofi, and UCB, Consultant of: AbbVie, Bristol, Biogen, Fresenius, Galapagos, Gebro, Janssen, and Lilly, Grant/research support from: Bristol Myers Squibb, MSD, Novartis, and Pfizer, Jasper Broen Consultant of: Galapagos, Gilead, UCB, and Novartis, Martin Welcker Speakers bureau: AbbVie, Aescu, Amgen, Biogen, BMS, Berlin Chemie, GSK, Hexal, Janssen, Medac, MSD, Mundipharma, Mylan, Novartis, Pfizer, Riemser, Sanofi, and UCB, Consultant of: AbbVie, Boehringer, BMS, Celgene, Galapagos, Gilead, GSK, Medac, Mylan, Novartis, Pfizer, Sanofi, and UCB, Grant/research support from: AbbVie, Actelion, Boehringer, Galapagos, Gilead, GSK, Hexal, Novartis, and UCB, Elizabeth Holdsworth Employee of: Adelphi Real World, Monia Zignani Employee of: Galapagos NV, Katrien Van Beneden Shareholder of: Galapagos NV, Employee of: Galapagos NV, Roberto Caporali Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Galapagos, Gilead, Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, Consultant of: Galapagos, Gilead, Janssen, Lilly, and MSD, Rieke Alten Consultant of: AbbVie, Amgen, Biogen, BMS, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and Roche

BackgroundThe goal of treatment for RA is achieving low disease activity and/or remission1,2; however, disease course and management can be complicated by additional factors that may be influenced by serostatus. Anti-citrullinated protein antibodies (ACPAs) and RF contribute to a more severe RA disease pattern3 and may be useful in predicting response to treatment.4 ACTION (AbataCepT In rOutiNe clinical practice; NCT02109666) and ASCORE (Abatacept SubCutaneOus in Routine Clinical PracticE; NCT02090556) were 2-year, international, observational, prospective, multicenter studies of IV and SC abatacept, respectively, for the treatment of RA in routine clinical practice.4,5 Previous analyses have shown that ACPA/RF double-positive serostatus was associated with better treatment outcomes compared with ACPA/RF double-negative serostatus.4–6ObjectivesTo assess the independent effect of ACPA or RF single seropositivity among patients with RA on achieving remission after treatment with abatacept for 2 years, and to compare outcomes among patients with single versus double serostatus.MethodsThis post hoc analysis included patients from ACTION and ASCORE who initiated IV (body weight–adjusted dosing) or SC abatacept (125 mg once weekly), respectively. Patients were stratified by baseline ACPA/RF status: ACPA+/RF− (ACPA+ only), ACPA/RF double positive (+/+), ACPA−/RF+ (RF+ only), and ACPA/RF double negative (−/−). DAS28 (CRP) and CDAI remission rates (defined as < 2.6 and 0–2.8, respectively) at 2 years for patients who were ACPA+ or RF+ only at baseline were assessed and compared with those who were +/+ and −/−. Patients with missing baseline ACPA/RF status were excluded. Last observation carried forward efficacy analyses were used to impute missing values.ResultsThis analysis included 1679 patients from ACTION (ACPA+ only, n = 98; +/+, n = 1028; RF+ only, n = 161; and −/−, n = 392) and 1748 patients from ASCORE (ACPA+ only, n = 184; +/+, n = 1079; RF+ only, n = 142; and −/−, n = 343). Across studies and serogroups, baseline demographics and disease characteristics were similar (data not shown). In both ACTION and ASCORE, a higher proportion of patients who were only ACPA+ achieved DAS28 (CRP) and CDAI remission at 2 years compared with patients who were only RF+ (Figure 1). Additionally, a similar proportion of patients who were only ACPA+ achieved DAS28 (CRP) and CDAI remission at 2 years compared with patients who were +/+. In contrast, a lower proportion of patients who were only RF+ achieved DAS28 (CRP) and CDAI remission at 2 years compared with patients who were +/+.ConclusionIn this post hoc analysis of real-world data from ACTION and ASCORE, ACPA positivity was associated with an increased likelihood of achieving DAS28 (CRP) and CDAI remission at 2 years. Patients who were ACPA+ only were as likely to achieve remission as +/+ patients, suggesting that RF serostatus had less influence than ACPA serostatus on remission status at 2 years. In line with this, patients who were RF+ only were less likely to achieve remission at 2 years. This is the first large, real-world study to show that ACPA positivity plays a more important role than RF positivity in achieving remission whilst on abatacept. These results highlight the importance of assessing baseline ACPA status when considering treatment options for patients with RA.References[1]Smolen JS, et al. Ann Rheum Dis 2020;79:685–99.[2]Fraenkel L, et al. Arthritis Care Res (Hoboken) 2021;73:924–39.[3]Katchamart, W, et al. Rheumatol Int 2015;35:1693–9.[4]Alten R, et al. Ann Rheum Dis 2021;80(suppl 1):OP0180.[5]Alten R, et al. Clin Rheumatol 2019;38:1413–24.[6]Alten R, et al. RMD Open 2017;3:e000345.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Medical writing and editorial assistance was provided by Rachel Rankin, PhD, of Caudex, and was funded by Bristol Myers Squibb. Study management provided by Syneos (CRO).Disclosure of InterestsRieke Alten Speakers bureau: AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Paid instructor for: AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Consultant of: AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Christiane Rauch Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Melanie Chartier Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, M.T. Nurmohamed Speakers bureau: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, Consultant of: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen, MSD, Pfizer, Sean Connolly Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Maya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Galapagos, Gilead, Pfizer, Grant/research support from: Gilead, Pfizer, UCB, Peter Peichl Speakers bureau: Janssen, GlaxoSmithKline, Xavier Mariette Consultant of: Bristol Myers Squibb, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi, UCB, Yusuf Patel: None declared, Sara Marsal Speakers bureau: Bristol Myers Squibb, Lilly, MSD, Novartis - Sandoz, Pfizer, Roche, Consultant of: AbbVie, Galapagos, Pfizer, Sanofi; IMIDomics (executive role), Grant/research support from: AbbVie, Bristol Myers Squibb, Galapagos, Janssen, Lilly, MSD, Novartis - Sandoz, Pfizer, Roche, Sanofi, UCB, Roberto Caporali Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Fresenius-Kabi, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB, Hedley Griffiths Consultant of: Amgen, Raimón Sanmartí Speakers bureau: AbbVie, Bristol Myers Squibb, Lilly, MSD, Pfizer, Roche, Sanofi, Grant/research support from: AbbVie, Bristol Myers Squibb, MSD, Pfizer, Roche, Bettina Bannert: None declared, Yedid Elbez Consultant of: Bristol Myers Squibb, Employee of: Signifience, Karissa Lozenski Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb

BackgroundVulnerable subjects, including systemic lupus erythematosus (SLE) patients have been prioritised to receive anti-SARS-CoV-2 vaccine. Questions have been raised about the effect of vaccines on immunity and their potential role as trigger for flare. Few data about the safety of these vaccines in SLE are availableObjectivesTo investigate the safety of different anti-SARS-CoV-2 vaccines in SLEMethodsData on SLE patients who have received anti-SARS-CoV-2 vaccine (from 12/2020 to 10/2021) were collected. Patients referred to 7 SLE tertiary centres (Lupus Clinic, ASST Pini-CTO, Milan; Nephrology Unit of Ospedale Giovanni Bosco, Turin; IRCCS Humanitas Research Hospital; Renal and Rheumatology Units, San Gerardo Hospital, Monza; ASST Spedali Civili Brescia; Lupus Clinic IRCCS Ospedale S. Raffaele, Milan, Italy; IRCCS Policlinico, Milan)Results452 SLE patients who had received anti-SARS-CoV-2 vaccines were included (91% BNT162b2 mRNA, 8% mRNA-1273, 1% ChAdOx1-S). 12 (3%) were off therapy, 71% were on low-medium dose prednisone, 83% on anti-malarials, 50% were treated with an immunosuppressant. 9 patients transiently discontinued therapy. 119 (26%) reported adverse symptoms after the first/second shot (12% and 21%) The most frequent were fever, local reaction, fatigue and arthralgias. Nineteen (4%) patients flared up after immunisation with a 7 days median time to relapse. Baseline demographics, SLE characteristics and therapy stratified by adverse events and disease flare are reported in Table 1. Anti-dsDNA positivity, moderate/high DAS before vaccine and use of Belimumab were significantly more frequent in the group of patients flared. These patients displayed a significantly higher rate of adverse events after vaccination. Flares consisted mainly musculoskeletal and constitutional manifestations (32%), involvement of renal (21%), cardio-respiratory (16%), hematological (16%) or mucocutaneous domains (10%) was less frequentTable 1.distribution of demographic and SLE characteristics according to sides effects and disease flares after vaccinationSide effects (n=119)No side effects (n=333)p-value (Disease flare (n=19)No disease flare (n=430)p-value (Age, years, median (IQR)46 (33.5-54)48 (35.7-57)0.1852 (39.5-56.0)48 (35.0-56.9)0.849Disease duration, months, median (IQR)138 (76-262)126 (73-193)0.30144 (122-242)127 (73-195)0.249MSK, %84.984.41.0078.984.80.514Mucocutaneus, %71.462.80.09457.964.50.624Renal, %42.052.30.06952.649.40.819NPSLE, %13.490.2155.310.40.708Cardiopulmonary %22.719.80.51026.320.30.562Hematological, %32.8331.0042.132.60.455Constitutional symptoms %48.7300.0003*26.335.30.473Gastrointestinal %4.23.30.7725.33.50.503Ophthalmic %0.83.30.19702.81.00Secondary APS %10.910.50.8645.310.90.708aPL positivity %26.233.60.13726.331.90.802Anti-dsDNA positivity %30.727.40.54555.627.10.0142*ESR, mm/h, median (IQR)14 (7-19)13 (7-22)0.73019 (10-24)13 (7-21)0.125CRP, mg/dL, median (IQR)0.5 (0.1-0.5)0.5 (0.3-0.6)0.3120.42 (0.13-0.50)0.50 (0.30-0.5)0.464Urinary abnormalities, %9.221.90.002321.118.50.764Moderate or high DAS before vaccine, %169.30.06026.310.40.0474*No therapy before vaccine, %03.60.0419*02.81.00At least 1 immunosuppressant, %6346.80.0027*73.750.10.059Mycophenolate, %31.923.10.06642.124.70.106Methotrexate, %5.96.61.005.36.51.00Belimumab, %21.813.50.0396*36.814.80.0184*Rituximab ever, %11.813.50.7515.313.40.490Prednisone, %74.8700.34778.970.90.607Conclusionour reassuring data confirm that anti-SARS-CoV-2 vaccine is safe in SLE patients and should be recommended in this clinical setting, as potential benefits widely outweigh the risk of adverse events. Treatment adjustment might be considered with the aim of minimizing the risk of side effects and/or flare, while ensuring a satisfying protection against infectionReferences[1]Tang W et al. The Use of COVID-19 Vaccines in Patients with SLE. Curr Rheumatol Rep. 2021 12;23:79.Disclosure of InterestsNone declared

BackgroundIn real-life setting, a greater number of elderly rheumatoid arthritis (RA) patients with impaired glomerular filtration rate (GFR) needs treatment with biologic or target synthetic disease-modifying anti-rheumatic drugs (b/tsDMARD) to achieve disease control and reduce NSAIDs intake. Long-term observational data from the real-life on the use of b/tsDMARD in these patients are scarce.ObjectivesThe aim of this study was to evaluate the retention rate of b/tsDMARD in RA patients with impaired GFR in real-life setting.MethodsData of RA patients treated with at least one b/tsDMARD were retrospectively analyzed form the national Italian GISEA registry from January 2016 to December 2021. Estimated-GFR (eGFR) was calculated with the Cockcroft-Gault equation at the time of any b/tsDMARD prescription. For the purpose of this study, patients were divided in two groups, patients with impaired GFR (eGFR ≤60) and patients with normal GFR (eGFR >60). The retention rate was calculated by the Kaplan-Meier method and compared between these two groups by a log-rank test.ResultsThe study population included 2443 treatment-line with b/tsDMARD from 1888 patients (female 80.4%, age 57±12 years, mean baseline CDAI 17±12, FR/ACPA+ 69.5%) who started a new b/tsDMARD. Disease characteristics are shown in Table 1. 288 treatments with b/tsDMARD were started in patients with impaired eGFR and 2155 in patients with normal eGFR. Compared to patients with eGFR >60, patients with eGFR ≤60 showed higher HAQ-DI (1.3±0.8 vs 1±0.8, pConclusionOur data show that impaired eGFR seems to not influence the persistence of b/tsDMARD treatment in RA patients.Disclosure of InterestsNone declared

BackgroundJanus kinase inhibitors (JAKi) are efficacious drugs for the control of disease activity in rheumatoid arthritis (RA). The effect on patient-reported outcomes (PROs) has been shown in randomized clinical trials, but is still largely unknown in real-life scenarios.ObjectivesTo assess the time to onset and magnitude of improvement across a number of different PROs in patients with RA treated with JAKi.MethodsPatients were selected from centres involved in the LORHEN Registry. Patients with a diagnosis of RA initiating a JAKi (Baricitinib or Tofacitinib) between May 2019 and February 2020 were clinically assessed at baseline, 8 weeks and 16 weeks with DAS28 and SDAI. PROs were collected at baseline, 2 weeks, 4 weeks, 8 weeks and 16 weeks from JAKi initiation. The PROs assessed at each timepoint were: Patient Global Assessment (PGA), General Health (GH), 0-100 mm visual analogue scale (VAS)-pain, VAS-fatigue, Health Assessment Questionnaire (HAQ), The Clinical Arthritis Activity (PRO-CLARA) questionnaire.ResultsThirty-eight patients (female 76%, mean age 57±15) were enrolled for a total of 152 visits for PROs assessments. Patients had received a median of 2 (IQR 1;3) previous conventional synthetic DMARDs (csDMARD) and a median of 2 (0;3) biological DMARDs. Mean disease duration at time of JAKi initiation was 10±9.5 years. JAKi was prescribed as combination therapy with a csDMARD in 20 (53%), concomitant glucocorticoids (GC) in 28 (73%) patients, at a mean dose of 6±2 mg/day. Twenty-one (55) patients were on regular analgesics. DAS28-ESR reduced from 4.5±0.9 at baseline to 2.6±0.9 at 8 weeks (pBy two weeks, all PROs had a significant reduction compared to baseline (Figure 1). For PGA, VAS-pain, VAS-fatigue a further significant reduction was observed by week 4 to then stabilize between week 8 and 16. GH and HAQ had a significant reduction by week 2 and remained stable thereafter. All PROs were significantly lower during all time-points compared to baseline. The PRO-CLARA Road score to assess physical function significantly improved starting from week 2 from a score of 4±2 to 2±2 at the end of follow-up. The PRO-CLARA self-administered tender joint count was stable at week 2 (mean score 4±2) but recorded an improvement from week 4 onwards (pFigure 1.Improvement of patient-reported outcomes over the period of observationConclusionTreatment with JAKi ensures a very rapid and persistent improvement of several PROs, including pain, fatigue and physical function, as early as 2 weeks treatment even in patients with long-standing RA treated with several lines of previous DMARDs.Disclosure of InterestsNone declared

BackgroundBaricitinib (BARI), an oral selective Janus kinase 1/2 inhibitor, is approved for treatment of adults with moderately-to-severely active rheumatoid arthritis (RA). BARI demonstrated efficacy in patients (pts) with RA who have inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) in a 24-week (wk) phase 3 study, RA-BEACON.1 BARI efficacy was evaluated up to 3 years (yrs) of treatment in a long-term extension (LTE) study, RA-BEYOND.2ObjectivesDisclose long-term efficacy of BARI 4 mg and 2 mg in bDMARD-IR pts in the completed study RA-BEYOND.MethodsIn RA-BEACON, pts were randomized 1:1:1 to BARI 4 mg, 2 mg, or PBO; pts with no response could be rescued after wk 16. Completers to wk 24 could enter with BARI 4 or 2mg RA-BEYOND for up to 360 wks (6.9 yrs). LTE data were analysed by treatment assigned at baseline in RA-BEACON as observed up to time of stepdown (if applicable), study discontinuation, or study completion, whichever occurred earlier. Efficacy response rates (RR) were assessed as proportions of pts with observed data up to wk 360 for low-disease activity (LDA) (SDAI ≤ 11, DAS28-hsCRP ≤ 3.2, CDAI ≤ 10), remission (REM) (SDAI ≤ 3.3, DAS28-hsCRP < 2.6, CDAI ≤ 2.8, Boolean), and physical functioning (HAQ-DI ≤ 0.5). No formal statistical comparisons were conducted.Results156, 152, and 140 pts entered the LTE (4 mg, 2 mg, and PBO, respectively). Pts in BARI 4 and 2 mg arms had higher LDA and REM RR vs PBO at LTE entry (wk 24) (Table 1). PBO-treated pts achieved comparable RR to pts in the BARI 4 mg arm by wk 48 (24 wks after switch to BARI 4 mg) and up to wk 360. Of pts enrolled to RA-BEYOND, approx. 50% in BARI 4 mg, 65% in 2 mg and 61% in PBO remained active at wk 156; 17%, 26% and 26% at wk 360, respectively. SDAI LDA RR were 47%/70% and 61%/74% for pts treated with BARI 4 mg and 2 mg, at wk 156 (yr 3)/ 360 (yr 6.9), respectively; SDAI REM RR were 15%/26% and 26%/26% for BARI 4 mg and 2 mg, at wk 156/360, respectively (Table 1). SDAI and CDAI had comparable RR. DAS-28CRP LDA RR were similar to SDAI and CDAI, while REM RR were about twice those of SDAI and CDAI. HAQ-DI ≤ 0.5 RR was 15%/26% (BARI 4 mg), 21%/15% (BARI 2mg), and 9%/3% (PBO) at 3/6.9 yrs.Table 1.Efficacy outcomes in RA-BEYONDTimeaN/n (%)LDAREMSDAICDAIDAS-28 CRPSDAICDAIDAS-28 CRPBooleanHAQ-DI ≤0.5Wk 24PBOb135/31 (23.0)138/32 (23.2)135/31 (23.0)135/6 (4.4)138/8 (5.8)135/14 (10.4)135/3139/6 (4.3)(2.2)BARI 2 mg148/42 (28.4)152/43 (28.3)148/38 (25.7)148/10 (6.8)152/10 (6.6)148/22 (14.9)148/9152/17 (11.2)(6.1)BARI 4 mg150/57 (38.0)156/60 (38.5)150/60 (40.0)150/14 (9.3)156/17 (10.9)150/37 (24.7)150/11 (7.3)156/17 (10.9)Wk 48PBO128/59 (46.1)129/58 (45.0)128/58 (45.3)128/14 (10.9)129/15 (11.6)128/31 (24.2)128/5130/6 (4.6)(3.9)BARI 2 mg139/54 (38.8)140/56 (40.0)139/53 (38.1)139/13 (9.4)140/14 (10.0)139/30 (21.6)139/11 (7.9)140/16 (11.4)BARI 4 mg147/70 (47.6)149/71 (47.7)147/68 (46.3)147/22 (15.0)149/19 (12.8)147/49 (33.3)147/14 (9.5)149/19 (12.8)Wk 156PBO84/47 (56.0)85/47 (55.3)84/45 (53.6)84/15 (17.9)85/14 (16.5)84/33 (39.3)84/985/8 (9.4)(10.7)BARI 2 mg98/60 (61.2)99/60 (60.6)98/58 (59.2)98/25 (25.5)99/27 (27.3)98/43 (43.9)98/13 (13.3)99/21 (21.2)BARI 4 mg76/36 (47.4)78/35 (44.9)76/37 (48.7)76/11 (14.5)78/13 (16.7)76/25 (32.9)76/978/12 (15.4)(11.8)Wk 360PBO33/26 (78.8)35/25 (71.4)34/27 (79.4)33/8 (24.2)35/9 (25.7)34/17 (50.0)34/636/1 (2.8)(17.6)BARI 2 mg38/28 (73.7)38/28 (73.7)38/27 (71.1)38/10 (26.3)38/8 (21.1)38/20 (52.6)38/539/6 (15.4)(13.2)BARI 4 mg27/19 (70.4)27/20 (74.1)27/20 (74.1)27/7 (25.9)27/7 (25.9)27/15 (55.6)27/427/7 (25.9)(14.8)N: Number of pts with observed data; n: Number of pts with response. aNumber of wks from randomisation. bTreatment groups as assigned at randomisation.ConclusionIn observed data, BARI maintained efficacy and normative physical function bDMARD-IR population up to 6.9 yrs (360 wks).References[1]Genovese MC et al. N Engl J Med. 2016; 374:1243-52[2]Wells AF et al. Rheumatol Ther. 2021; 8:987–1001Disclosure of InterestsRoberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Eli Lilly and Company, Galapagos, Pfizer, Fresenius-Kabi, MSD, UCB, Roche,Janssen, Novartis, Sandoz, Consultant of: Abbvie, Amgen, BMS, Celltrion, Eli Lilly and Company, Galapagos, Pfizer, MSD, UCB, Janssen, Novartis, Sandoz, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: Abbvie, Amgen, Eli Lilly and Company, Novartis, Roche, SoBi, Sanofi, Raimón Sanmartí Speakers bureau: Eli Lilly and Company, Grant/research support from: Eli Lilly and Company, Tsutomu Takeuchi Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan K.K.; Gilead Sciences, Inc. Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Co.; Novartis Pharma Co.; Pfizer Japan Inc.; Sanofi K.K.; UCB Japan Co., Ltd., Consultant of: AbbVie Japan GK, Astellas Pharma, Inc.; Chugai Pharmaceutical Co, Ltd.; Eli Lilly Japan K.K.; Eisai Co., Ltd.; Gilead Sciences, Inc.; Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Corp., Pfizer Japan Inc., Grant/research support from: AbbVie Japan GK, Asahikasei Pharma Corp., Chugai Pharmaceutical Co, Ltd., DNA Chip Research Inc.; Eisai Co., Ltd., Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Corp., UCB Japan Co., Ltd., Daojun Mo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Ewa Haladyj Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Liliana Zaremba-Pechmann: None declared, Peter C. Taylor Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Inc, Roche, and Sanofi, Grant/research support from: Celgene and Galapagos

BackgroundA treat-to-target approach for RA management is recommended.1,2 However, up to half of patients discontinue DMARD treatment within 18 months.2 Predictive biomarkers, such as anti-citrullinated protein antibodies (ACPAs) and RF, may be useful to stratify patients to the most appropriate treatment. ACTION (AbataCepT In rOutiNe clinical practice; NCT02109666) and ASCORE (Abatacept SubCutaneOus in Routine Clinical PracticE; NCT02090556) were 2-year, international, observational, prospective, multicenter studies of IV and SC abatacept, respectively, for the treatment of RA in routine clinical practice.3,4 Higher retention has been previously reported in patients with double ACPA/RF seropositive RA compared with double ACPA/RF seronegative RA.3,4ObjectivesTo assess the independent effect of ACPA or RF single seropositivity on abatacept retention in patients with RA receiving abatacept in a post hoc analysis of ACTION and ASCORE.MethodsThis post hoc analysis included patients aged ≥ 18 years, with active moderate-to-severe RA (ACR/EULAR 2010 criteria) who initiated IV (body weight–adjusted dosing) or SC (125 mg once weekly) abatacept.3,4 Patients were stratified by baseline ACPA/RF status: ACPA+/RF− (ACPA+ only), ACPA/RF double positive (+/+), ACPA−/RF+ (RF+ only), and ACPA/RF double negative (−/−). Abatacept retention rate at 2 years was estimated by Kaplan–Meier (KM) analysis.ResultsPatients with ACPA/RF serostatus data from the ACTION and ASCORE studies (N = 1679 and N = 1748, respectively) were evaluated. Baseline demographic and disease characteristics were similar across studies and serostatus groups (Table 1). In patients with ACPA+ only RA, abatacept retention rates were similar to the +/+ group and greater than the RF+ only and −/− groups (Figure 1). In ASCORE (Figure 1A), retention rates were significantly higher in ACPA+ only and +/+ groups when compared with the −/− group. In contrast, retention rates for patients with RF+ only RA were not significantly different vs −/− patients. Results were similar in ACTION, although the higher retention in the ACPA+ group did not reach statistical significance (Figure 1B).Table 1.Baseline demographics and disease characteristics by ACPA/RF status for the ASCORE and ACTION studiesASCORE+/+RF+ onlyACPA+ only−/−(n = 1079)(n = 142)(n = 184)(n = 343)Age, years57.1 (12.8)58.2 (11.8)57.4 (13.5)57.8 (13.9)DAS28 (CRP)4.7 (1.2)4.6 (1.1)4.4 (1.0)4.8 (1.2)CDAI26.6 (12.5)25.8 (12.0)23.6 (10.9)28.2 (13.2)SDAI28.1 (13.0)27.2 (12.4)24.4 (10.8)29.7 (13.9)ACTION+/+RF+ onlyACPA+ only−/−(n = 1028)(n = 161)(n = 98)(n = 392)Age, years58.2 (12.0)58.4 (13.4)58.5 (14.0)57.0 (13.3)DAS28 (CRP)4.9 (1.1)5.0 (1.1)4.9 (1.0)5.0 (1.1)CDAI28.7 (12.2)29.2 (12.4)28.7 (11.5)30.1 (12.9)SDAI30.4 (13.1)31.2 (13.4)29.8 (11.5)31.7 (13.4)Data are mean (SD). Patients with missing data for baseline ACPA/RF status are excluded.ConclusionIn this post hoc analysis of the real-world ACTION and ASCORE studies, ACPA positivity was associated with an increased likelihood of retention over 2 years. Patients with ACPA+ only RA were equally as likely to be retained on abatacept as patients with ACPA/RF double positivity. In contrast, patients with RF+ only RA were less likely to be retained on abatacept over 2 years. These findings suggest that ACPA positivity played a more important role than RF positivity in abatacept retention. The higher retention seen in patients with ACPA+ only vs RF+ only disease demonstrates the key role of ACPA in RA and supports the importance of precision medicine in treating patients.References[1]Fraenkel L, et al. Arthritis Care Res (Hoboken) 2021;73:924–39.[2]Smolen JS, et al. Ann Rheum Dis 2020;79:685–99.[3]Alten R, et al. Clin Rheumatol 2019;38:1413–24.[4]Alten R, et al. Ann Rheum Dis 2021;80(suppl 1):OP0180.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Medical writing and editorial assistance was provided by Fiona Boswell, PhD, of Caudex, and was funded by Bristol Myers Squibb. Study management provided by Syneos (CRO).Disclosure of InterestsRieke Alten Speakers bureau: AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Paid instructor for: AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Consultant of: AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Christiane Rauch Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Melanie Chartier Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, M.T. Nurmohamed Speakers bureau: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, Consultant of: AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen, MSD, Pfizer, Sean Connolly Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Maya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Galapagos, Gilead, Pfizer, Grant/research support from: Gilead, Pfizer, UCB, Peter Peichl Speakers bureau: GlaxoSmithKline, Janssen, Xavier Mariette Consultant of: Bristol Myers Squibb, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi, UCB, Yusuf Patel: None declared, Sara Marsal Speakers bureau: Bristol Myers Squibb, Lilly, MSD, Novartis - Sandoz, Pfizer, Roche, Consultant of: AbbVie, Galapagos, Pfizer, Sanofi; IMIDomics (executive role), Grant/research support from: AbbVie, Bristol Myers Squibb, Galapagos, Janssen, Lilly, MSD, Novartis - Sandoz, Pfizer, Roche, Sanofi, UCB, Roberto Caporali Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Fresenius-Kabi, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB, Hedley Griffiths Consultant of: Amgen, Raimón Sanmartí Speakers bureau: AbbVie, Bristol Myers Squibb, Lilly, MSD, Pfizer, Roche, Sanofi, Grant/research support from: AbbVie, Bristol Myers Squibb, MSD, Pfizer, Roche, Bettina Bannert Speakers bureau: Novartis Pharma Schweiz AG, Yedid Elbez Consultant of: Bristol Myers Squibb, Employee of: Signifience, Karissa Lozenski Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb.

BackgroundComplex regional pain syndrome type-1 (CRPS-1) is a severely disabling pain syndrome characterized by sensory and vasomotor disturbance, swelling, and functional impairment. Persistence of signs and symptoms has been observed in up to 64% of cases until 5.8 yrs after the onset of manifestations. Long-term disability, such as irreversible functional limitation, has been reported in up to 28% of cases with severe consequences on workability. No scores are validated to evaluate residual disability. Bisphosphonates have the best efficacy profile, compared with other therapeutic approaches, but data on long-term effectiveness are lacking.ObjectivesTo retrospectively evaluate long-term residual disability in patients with CRPS-1 of hand or foot after treatment with IV Neridronate (IVNer). To identify predictors of residual disability. To quantify disease outcomes, such as patient’s subjective perception and residual pain. To assess long-term safety profile.MethodsWe retrospectively collected data of patients affected by CRPS-1, treated with IVNer, referred to a tertiary Rheumatology Centre between Feb 2013 and Dec 2020. Visual analogue scale (VAS) and McGill Questionnaire (McGQ) were used for pain assessment. Disabilities of the Arm, Shoulder and Hand (DASH) and American Orthopaedic Foot and Ankle Society’s (AOFAS) ankle-hindfoot scale for hand and foot involvement, respectively, were administered to explore disability through a phone survey. This kind of investigation was preferred for Covid pandemic.Results106 patients with definite diagnosis of CRPS-1 were included, mean age±standard deviation 55.6±13 yrs, 67% females, mean follow up duration 56.3 months (range 14-94), 46.2% with hand involvement. The mean VAS score before treatment onset was 55.8±23.4mm, while the McGQ was 12.9±6.7 in the sensory domain, 4.9±3.3 in the affective domain and 17.8±9.2 on the total score.Based on the patient’s subjective perception and the proposed semi-quantitative scale, 77.4% described themselves as fully recovered (FR), 15% partially recovered (PR), and 7.6% with persistent disease (PD). Comparison between baseline and follow-up VAS shows a significant reduction (55.8±23.4 vs 15.1±26.4, pPain assessment by McGQ showed a significant improvement in global score (baseline vs follow-up 17.8±9.2 vs 3.9±7.8, pAccording to DASH score, 79.2% of the patients were FR, 3.8% had some difficulties, but with overall preserved use of the upper limb, and 17.0% had permanent functional disability.According to AOFAS ankle-hindfoot scale 76.4% of patients were FR, 16.0% had partial recovery, and 7.6% had severe functional impairment.Percentages of DASH and AOFAS scores showed a complete accordance with patients’ subjective perception (Figure 1a and b).The only predictor of long-term functional impairment for CRPS-1 in the hand was a delayed treatment compared to symptoms onset (p=0.02). No predictors were found for foot localization.No patients reported the occurrence of osteonecrosis of the jaw or atraumatic fractures/atypical fracture features.Figure 1.ConclusionIVNer maintained a good long-term effectiveness and safety profile in the treatment of CRPS-1. The effectiveness of IVNer is maintained on both pain symptoms and function, in terms of reductions in the VAS, McGQ and in hand and foot disability scores.References[1]Varenna M et al. Rheumatology 2013[2]Padua R. et al. J Hand Surg. Br. Eur. 2003[3]Leigheb M et al. Acta Biomed. Atenei Parm. 2016Disclosure of InterestsNone declared

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line treatment of axial Spondyloarthritis (axSpA) and biological disease-modifying antirheumatic drugs (bDMARDs) are effective in the management of patients refractory to NSAIDs. However, in some cases the introduction of bDMARDs is limited by absolute contraindications or patient opposition. Beyond the well-known anti-osteoclastic properties, bisphosphonates (BPs) can exert their benefits through other mechanisms, including reduction of proinflammatory cytokines (such as IL6 and TNFα), and modulation of macrophage and osteoblast activity.ObjectivesTo examine the potential therapeutic properties of a BP, IV neridronate (IVNer), in patients with axSpA refractory to NSAIDs and not eligible for a second-line therapy with bDMARDs.MethodsWe retrospectively collected data of patients affected by axSpA according to ASAS classification criteria, treated with IVNer, referred to a tertiary Rheumatology Centre between Sept 2015 and Dec 2021. Patients with active disease, as defined by a BASDAI score ≥4, with active sacroileitis (SI) on MRI (according to ASAS MRI definition of active SI), who had failed/were intolerant to NSAIDs and not eligible for bDMARDs, were recruited. IVNer (100 mg) was given intravenously on Days 1, 4, 7, and 10, over 3 h in 500 ml of 0.9% saline. Response to IVNer was evaluated after 60 days from the last infusion as the mean change from baseline of BASDAI and visual analogue scale (VAS) pain score, and the improvement of MRI imaging.ResultsWe included 30 patients (77% females, mean age±SD 39.0±16.8 yrs, and mean disease duration of 24±14.4 months (range 1.0-298). Fourteen had ankylosing spondylitis (AS), six had undifferentiated SpA, two had enteropathic arthritis, one had non-radiographic axSpA, and seven had axial psoriatic arthritis. 50% had axial involvement, 30% axial and peripheral arthritis, and 20% had axial and enthesis involvement. Eleven were HLA-B27 positive. On MRI evaluation, 43% had monolateral SI, 57% bilateral SI and 7% had erosions. Among the reasons of ineligibility to bDMARDs, 6 patients have concurrent solid tumor, 11 had comorbidities contraindicating bDMARDs, and 12 preferred not to undergo to bDMARDs. Mean BASDAI significantly decrease after IVNer (5.86±1.98 vs 3.52±2.39, p=0.0002, Figure 1a), as well as VAS pain score (6.14±1.92 vs 3.18±2.62, pFigure 1.ConclusionIVNer was effective in reducing disease activity measured by BASDAI and VAS pain score in patients with axSpA refractory to NSAIDs and not eligible for bDMARDs. When recommended second-line treatments are contraindicated or according to patients’ preference, IVNer can be considered as a potential alternative therapeutic option. Further evaluations in controlled trials are needed to confirm these results.References[1]Varenna M, Rheumatology 2014.[2]Maksymowych WP et al, Ann Rheum Dis. 2019Disclosure of InterestsNone declared

BackgroundRheumatic musculoskeletal diseases (RMD) are pathological conditions characterized by an impaired immunological system that is determinant both in the pathogenesis and in the inadequate response to infections. The use of disease-modifying anti-rheumatic drugs (DMARDs), which include conventional synthetic (cs) or biologic and targeted synthetic (b/ts) DMARDs, contribute to compromise immunological reactivity.ObjectivesTo analyze the immune response to SARS-CoV-2 in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) receiving treatment with DMARDs and to investigate the effect of the different classes of drugs on humoral and cellular response.MethodsPatients were tested for anti-SARS-CoV-2 IgG, IgM and IgA antibodies to nucleoprotein (N) and receptor-binding domain (RBD) through ELISA and neutralization assays. Then, we performed a flow cytometry analysis of monocytes, NK cells, B and T lymphocytes from PBMCs of serologically positive patients. We also included a cohort of non-RMD individuals recovered from COVID-19 as a reference group of non-immunosuppressed subjects. A first recruitment occurred in May-June 2020 (T1) and a second recruitment, 3-4 months after (T2), allowed to evaluate the persistence of the antibody response over time and to investigate the cellular immune response to SARS-CoV-2 in RMD patients having resolved the infection.ResultsDuring T1, 358 patients with RA (n=200) or SpA (n=158) were recruited. Mean age was 52.8, 64% were female. All patients were treated with DMARDs, 299 with b/tsDMARDs and 59 received csDMARDs alone. One third was also receiving corticosteroids (CS). At T2, 36 subjects were recruited. We found a seroprevalence rate of 18.4%, which did not significantly differ between RA and SpA groups, and between patients treated with b/ts-DMARD or csDMARDs, either alone or in combination with CS (Table 1). Antibody levels of RMD patients were lower than non-RMD individuals (Figure 1), with CTLA4-Ig-treated patients having the lowest IgG levels. This difference was less marked in symptomatic RMD patients. 72% of seropositive patients elicited neutralizing sera. Despite an overall decrease in anti-RBD and anti-N titers, more than two-third of patients maintained antibodies titers above positivity threshold at T2. Concerning cellular response, we found that CD8+ T-cells frequency was overall comparable between RMD and non-RMD convalescents, and did not differ in b- or cs-DMARD treated ones. Conversely, CD4+ T-cell frequencies were significantly lower in RMD patients, especially those treated with anti-IL6R and CTLA4-Ig. B-cell subpopulations (class-switched, memory, and IgG+ memory B-cells) had sustained frequencies in anti-TNFα treated patients, while they had a trend of reduction in patients treated with anti-IL6R and CTLA4-Ig.Table 1.Anti-RBD seroprevalenceTotalSeropositive, n(%)IgM (n)(%)IgG (n)(%)IgA (n)(%)COVID19 symptomatic772532.51924.71722.11722.1COVID19 asymptomatic2814114.6*238.2*134.6 *269.3*RA20036192311.520102713.5SpA15830191912106.31610.1b/ts-DMARD2995518.43511.72483612cs-DMARD591118.6711.9610.2711.9csDMARD+b/tsDMARD1122623.287.187.198a-TNFa1733721.42514.5169.12112.1a-IL-6R35822.9514.3617.1822.9CTLA4-Ig42511.937.112.447.1*P value < 0,005Figure 1.Magnitude of the anti-RBD and anti-N antibody responseConclusionOur data provide a comprehensive picture of the humoral and cellular immune responses to SARS-CoV-2 infection in RMD patients. We showed that DMARDs treatments did not alter a successful antibody response to the virus and did not hamper the antibody neutralizing ability. However, the magnitude of antibody response was slightly reduced compared to non-RMD individuals, especially in patients receiving CTLA4-Ig. We did not observe marked differences in the B- and T-cell populations between RMD patients compared to non-RMD individuals. However, in patients receiving anti-TNFα we found a higher relative abundance of effector adaptive population compared to other bDMARDs.AcknowledgementsThe project was co-financed by Lombardy 2014-2020 Operational Program under the European Regional Development Fund.Disclosure of InterestsNone declared

BackgroundAccumulating evidence suggests that poor mental health is one of the most common comorbidities of both rheumatoid arthritis (RA) and osteoarthritis (OA) [1]. Even if underpinning RA and OA are different genetic, structural, mechanical, and immunologic pathways involved in their pathogenesis, poor mental health, and joint involvement are intertwined and negatively affect their mutual course by contributing to global disability. Thus, new insights into mechanisms that link these disorders are needed to identify new actionable biomarkers to drive more personalized therapeutic strategies. Amidst potential mediators, extracellular vesicles (EVs) play a central role in terms of communication between cells, they cross the blood-brain barrier and based on their cargos can affect the recipient cell function [2].ObjectivesTo isolate EVs from synovial fluid (SF) in RA and OA patients and to evaluate if and how these EVs can alter in vitro synaptic transmission of murine hippocampal neurons.MethodsIn this cross-sectional pilot study, consecutive adult RA and primary OA who were referred to the Rheumatology Unit for aspiration of joint effusion were enrolled. Demographic and clinical variables and mental health rating scales were collected. Discarded SF were collected and EVs were isolated and analyzed by Malvern NanoSight NS300 system to obtain information on their number and size. Afterwards, DIV14 cultured wild-type hippocampal neurons were exposed for two hours to OA- and RA-EVs at low and high concentration EVs. Thus, miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs), which reflects glutamatergic and GABA-ergic activity respectively, were examined by exploiting patch-clamp recordings in the whole-cell configuration. Frequency and amplitude were analyzed to evaluate potential changes at the presynaptic or postsynaptic compartment. Mann Whitney test was used to compare two different samples.ResultsEight RA patients (7 female, mean age 57 yrs), and 5 primary OA (4 female, mean age 60 yrs) were recruited for SF aspiration. The mean VAS pain was 7.25 in RA and 6.5 in OA. No statistically significant differences were found between the two groups in mean rating scale scores although patients affected by RA had more severe depressive symptoms (Montgomery Asberg Depression Rating Scale -MADRS- means scores: 16.57) with respect OA group (MADRS mean scores: 10). The Nanoparticle tracking analysis showed that RA-EVs were significantly more in number compared to OA-EVs (Figure 1 A), mimicking more inflammation, while no significant difference in size was observed. Analysis of miniature events revealed the occurrence of two different changes. High concentration of OA-EVs has led to an increased amplitude of excitatory events, meaning an increased susceptibility of neurons to glutamate in the post-synaptic compartment (Figure 1 B). Whereas low concentration of RA-EVs has led to a decreased frequency of inhibitory events, which reflects a reduced function of GABA-ergic synapse in the pre-synaptic compartment (Figure 1 C).Figure 1.ConclusionOur results suggest that SF-derived EVs from OA and RA patients lead to different specific changes of neurotransmission, with different concentration needed to alter neuronal spontaneous activity in post-synaptic and pre-synaptic compartment, respectively. EVs may provide insight into the pathogenesis of joint-brain communication in RA and OA, unraveling specific pathways thus allowing targeted therapies for neuropsychiatric involvement.References[1]Lancet 2017;390(10100): 1211–1259[2]FASEB Bioadv 2021;3(9):665-675Disclosure of InterestsLavinia A. Coletto: None declared, Francesca Ingegnoli: None declared, Clara Cambria: None declared, Laura Cantone: None declared, Orazio De Lucia: None declared, Roberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Galapagos, Lilly, Pfizer, Fresenius-Kabi, MSD, UCB, Roche,Janssen, Novartis, Sandoz, Consultant of: Abbvie, Amgen, BMS, Celltrion, Galapagos, Lilly, Pfizer, MSD, UCB, Janssen, Novartis, Sandoz, Valentina Bollati: None declared, Massimiliano Buoli: None declared, Flavia Antonucci: None declared.

BackgroundFilgotinib (FIL) is a Janus kinase 1 preferential inhibitor for the treatment of moderate to severe rheumatoid arthritis (RA)1. The recommended dose for adults with RA is 200 mg (FIL200); however, a starting dose of 100 mg (FIL100) is recommended for those aged ≥75 years (y) in view of limited clinical experience1. An important consideration is the generally higher incidence of adverse events (AEs) in the elderly due to comorbidities.ObjectivesTo evaluate the efficacy and safety of FIL100 and FIL200 in patients with RA aged ≥75 y.MethodsFINCH 4 (NCT03025308) is an ongoing phase 3 open-label LTE study of FIL100 and FIL200 for RA. Eligible patients completed a prior phase 3 randomized double-blind study of FIL lasting 52 weeks (FINCH 1 or 3) or 24 weeks (FINCH 2). In this post hoc analysis, safety and efficacy were assessed in patients aged ResultsAt LTE Week 48, 52% and 44% of patients aged Figure 1.The exposure-adjusted incidence rate (EAIR) of serious AEs and AEs of special interest (AESI) was generally higher in patients aged ≥75 y than Table 1.Exposure-adjusted incidence rate (95% CI) of AEs at Week 48 as events per 100 years of exposureFIL200FIL100Age, years≥75≥75n=1469n=61n=1136n=63(PYE 2253.9)(PYE 92.2)(PYE 1753.7)(PYE 98.4)With prior FIL exposure, n (%)1142 (77.7)53 (86.9)830 (73.1)33 (52.4)TEAE48.3 (45.5, 51.3)55.3 (42.1, 72.8)48.7 (45.5, 52.1)42.7 (31.6, 57.8)Serious TEAE6.8 (5.8, 8.0)17.4 (10.6, 28.3)7.4 (6.2, 8.7)14.2 (8.4, 24.0)AE leading to premature study discontinuation2.9 (2.3, 3.7)9.8 (5.1, 18.8)3.9 (3.1, 5.0)4.1 (1.5, 10.8)AE leading to death0.5 (0.3, 0.9)3.3 (0.7, 9.5)*0.3 (0.2, 0.8)0.0 (0.0, 3.8)Infections28.8 (26.6, 31.1)29.3 (20.1, 42.7)27.4 (25.0, 29.9)26.4 (18.0, 38.8)Serious infections1.6 (1.2, 2.2)2.2 (0.5, 8.7)1.7 (1.1, 2.4)3.1 (1.0, 9.5)Herpes zoster1.6 (1.2, 2.3)2.2 (0.5, 8.7)1.0 (0.6, 1.6)3.1 (1.0, 9.5)Adjudicated major adverse cardiovascular event0.4 (0.2, 0.7)2.2 (0.5, 8.7)0.5 (0.2, 0.9)1.0 (0.1, 7.2)Venous thrombotic and embolic events0.3 (0.1, 0.6)2.2 (0.5, 8.7)0.2 (0.1, 0.5)1.0 (0.1, 7.2)Malignancy excluding NMSC0.7 (0.4, 1.2)4.3 (1.6, 11.6)0.7 (0.4, 1.2)3.1 (1.0, 9.5)NMSC0.4 (0.2, 0.8)1.1 (0.0, 6.0)0.2 (0.1, 0.6)0.0 (0.0, 3.8)*Cause of death: esophageal carcinoma; cardiovascular; unknown. FIL(100/200), filgotinib (100/200 mg); NMSC, nonmelanoma skin cancer; PYE, patient years of exposure; (TE)AE, (treatment-emergent) adverse eventConclusionIn the ≥75 y group, response rates for key efficacy measures remained stable to Week 48 and were generally higher with FIL200 vs FIL100. The incidence of serious AEs and AESI was higher in those aged ≥75 than References[1]Filgotinib SmPCAcknowledgementsThe FINCH studies were funded by Gilead Sciences (Foster City, CA, United States). We thank the physicians and patients who participated in the studies. Medical writing support was provided by Debbie Sherwood, BSc (Aspire Scientific Ltd, Bollington, UK) and funded by Galapagos NV (Mechelen, Belgium).Disclosure of InterestsDaniel Aletaha Speakers bureau: AbbVie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, and Sandoz, Consultant of: AbbVie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, and Sandoz, Grant/research support from: AbbVie, Amgen, Lilly, Novartis, Roche, SoBi, and Sanofi, Rene Westhovens Speakers bureau: Celltrion, Galapagos, and Gilead, Consultant of: Celltrion, Galapagos, and Gilead, Bernard Combe Speakers bureau: AbbVie, BMS, Celltrion, Eli Lilly, Gilead-Galapagos, Janssen, MSD, Novartis, Pfizer, and Roche-Chugai, Consultant of: AbbVie, Celltrion, Eli Lilly, Gilead-Galapagos, Janssen, and Roche-Chugai, Jacques-Eric Gottenberg Consultant of: AbbVie, BMS, Galapagos, Gilead, Lilly, and Pfizer, Grant/research support from: BMS and Pfizer, Maya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Galapagos, Gilead, and Pfizer, Grant/research support from: Gilead and Pfizer, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, and UCB, Consultant of: AbbVie, Amgen, BMS, Celltrion, Fresenius-Kabi, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB, José A Gómez-Puerta Speakers bureau: AbbVie, BMS, Galapagos, GSK, Lilly, MSD, Novartis, Pfizer, Roche, and Sanofi, Consultant of: GSK, Roche, and Sanofi, Paul Van Hoek Employee of: Galapagos, Vijay Rajendran Employee of: Galapagos, Pieter-Jan Stiers Shareholder of: Galapagos, Employee of: Galapagos, Thijs Hendrikx Employee of: Galapagos, Gerd Rüdiger Burmester Consultant of: AbbVie, Amgen, BMS, Galapagos, Lilly, MSD, Pfizer, Roche, and Sanofi, Yoshiya Tanaka Speakers bureau: AbbVie, Amgen, Astellas, Astra-Zeneca, Boehringer-Ingelheim, BMS, Chugai, Eisai, Eli Lilly, Gilead, Mitsubishi-Tanabe, and YL Biologics, Consultant of: AbbVie, Ayumi, Daiichi-Sankyo, Eli Lilly, GSK, Sanofi, and Taisho, Grant/research support from: AbbVie, Asahi-Kasei, Boehringer-Ingelheim, Chugai, Corrona, Daiichi-Sankyo, Eisai, Kowa, Mitsubishi-Tanabe, and Takeda

BackgroundSubcutaneous (SC) CT-P13 is the first and only subcutaneous formulation of infliximab (IFX) approved by the EMA.1 In the pivotal study (NCT03147248), non-inferiority of SC IFX to intravenous (IV) was demonstrated in rheumatoid arthritis (RA) patients using 28-joint Disease Activity Score (DAS28) C-reactive protein (CRP) improvement at Week 22, with a statistically significant treatment difference of 0.27 (95% CI 0.02, 0.52) favoring the SC versus the IV arm.2,3 At Week 30, numerical differences in efficacy outcomes were shown between SC and IV IFX favoring SC IFX. IV group patients switched to SC IFX by Week 30, and the difference between the groups was reduced at Week 54.2ObjectivesTo investigate whether there was a statistically significant difference between SC and IV IFX at Weeks 30 and 54 in the phase 3 pivotal study of CT-P13 SC using conservative missing imputation methods.MethodsPatients with active RA who had an inadequate response to MTX received IV IFX 3mg/kg at Weeks 0 and 2 for induction and were randomized at a 1:1 ratio to receive SC IFX 120mg every 2 weeks or IV 3mg/kg every 8 weeks thereafter for maintenance. Patients who were randomized to receive IV IFX switched to SC at Week 30. In this post-hoc analysis, non-responder imputation (NRI) and last observation carried forward (LOCF) methods were used to investigate whether the difference in efficacy outcomes between SC and IV IFX at Weeks 30 and 54 was statistically significant. Assessments included EULAR (CRP/ESR)/ACR response; remission rate and low disease activity (LDA) rate based on DAS28 (CRP/ESR), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI); Boolean remission rate; and the proportion of patients achieving a minimal clinically important difference (MCID) in Health Assessment Questionnaire (HAQ).ResultsOf the 343 randomized patients, 165 patients who received SC IFX and 174 patients who received IV IFX from the efficacy population were included in the analysis. There was a statistically significant difference in SC IFX compared to IV treated patients at Week 30 using both NRI and LOCF methods in almost all the clinical variables. However, the difference in efficacy outcomes between SC IFX and IV was reduced at Week 54 after the IV group switched to SC. This supports the improved efficacy of SC IFX at Week 30. Some of the key results (EULAR [CRP] responses, LDA rates based on DAS28 [CRP], CDAI, and SDAI) were presented in Figure 1. Analysis using LOCF and NRI methods yielded consistent results across most of the efficacy outcomes.Figure 1.Comparison of clinical outcomes between SC IFX and IV IFX in patients with active rheumatoid arthritis.*PP-value for difference in proportion between SC and IV treatment group was obtained by asymptotic Wald test.Low disease activity based on DAS28 (CRP) (< 3.2), CDAI (eatment group AI (≤ 11.0).ConclusionStatistical analyses using conservative missing imputation methods showed significantly greater improvements in clinical outcomes with SC IFX compared to IV at Week 30 in patients with RA. Between-group differences was reduced at Week 54, suggesting improved responses after switching from IV to SC.References[1]Remsima summary of product characteristics. https://www.ema.europa.eu/en/documents/product-information/remsima-epar-product-information_en.pdf. Published 2021. Accessed 10 January 2022.[2]Westhovens R, Wiland P, Zawadzki M, et al. Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial. Rheumatology (Oxford). 2021;60(5):2277-2287.[3]Combe B, Allanore Y, Alten R, et al. Comparative efficacy of subcutaneous (CT-P13) and intravenous infliximab in adult patients with rheumatoid arthritis: a network meta-regression of individual patient data from two randomised trials. Arthritis Res Ther. 2021;23(1):119.Disclosure of InterestsArnaud Constantin Speakers bureau: Abbvie, Amgen, Boehringer, Celltrion, Galapagos, Janssen, Lilly, Novartis, Sanofi, UCB, Consultant of: Abbvie, Amgen, Boehringer, Celltrion, Galapagos, Janssen, Lilly, Novartis, Sanofi, UCB, Roberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Galapagos, Lilly, Pfizer, Fresenius-Kabi, MSD, UCB, Roche,Janssen, Novartis, Sandoz, Consultant of: Abbvie, Amgen, BMS, Celltrion, Galapagos, Lilly, Pfizer, MSD, UCB, Janssen, Novartis, Sandoz, Christopher John Edwards Speakers bureau: Abbvie, Astra Zeneca, Celltrion, Chugai, Fresenius, Galapagos, Gilead, GSK, Lilly, Janssen, Pfizer, Roche, Consultant of: Abbvie, Astra Zeneca, Chugai, Galapagos, Gilead, GSK, Lilly, Janssen, Pfizer, Roche, Grant/research support from: Celltrion, Pfizer, Abbvie, Joao Eurico Fonseca Speakers bureau: Abbvie, Ache, Janssen, Lilly, Medac, Novartis, Pfizer, Consultant of: Abbvie, Celltrion, Janssen, Lilly, Pfizer, Grant/research support from: Abbvie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Florenzo Iannone Speakers bureau: Abbvie, BMS, Celltrion, Galapagos, MSD, Eli-Lilly, Janssen, Novartis, Pfizer, UCB, Consultant of: Abbvie, BMS, Celltrion, Galapagos, MSD, Eli-Lilly, Janssen, Pfizer, Grant/research support from: BMS, MSD, Edward Keystone Speakers bureau: Amgen, AbbVie, Celltrion, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi Genzyme, Consultant of: AbbVie, Amgen, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis, Grant/research support from: Amgen, Merck, Pfizer Pharmaceuticals, Hendrik Schulze-Koops Consultant of: Celltrion, Taeksang Kwon Employee of: Celltrion Healthcare, Seungmin Kim Employee of: Celltrion Healthcare, Sangwook Yoon Employee of: Celltrion Healthcare, Dong-Hyeon Kim Employee of: Celltrion Healthcare, Gahee Park Employee of: Celltrion Inc., DaeHyun Yoo Speakers bureau: Celltrion, Celltrion Healthcare

BackgroundAntiphospholipid Syndrome (APS) is a rare autoimmune disease characterized by thrombotic events and/or pregnancy morbidities in the presence of confirmed positivity for antiphospholipid antibodies (aPL). Complement was demonstrated to be involved in aPL-related pregnancy loss in animal models and several groups investigated the significance of complement levels in human disease. C3 and C4 serum levels were assessed in several cohorts of pregnant patients with APS and/or aPL positivity in order to relate complement consumption with adverse pregnancy outcome (APO).According to some authors, hydroxychloroquine (HCQ) can control the activation of the complement system, improve pregnancy outcome and reduce aPL title.ObjectivesThis study was designed to verify the effect of HCQ in addition to low dose aspirin (LDA) + low molecular weight heparin (LMWH) treatment in a multicenter cohort of primary APS (PAPS) and aPL carriers pregnant women and the possible correlation with preconception serum C3/C4 levels.MethodsMedical records of pregnant women with confirmed positivity for aPL antibodies attending twelve referral centers from January 2010 to December 2020 were retrospectively evaluated. We considered as aPL-related APO: spontaneous abortions (ResultsWe have analyzed 164 singleton PAPS/aPL carrier pregnancies (22 aPL carriers - 13%) in 128 patients: all were treated with combination therapy (LDA+LMWH), and in 30 HCQ was added. 58 pregnancies (43%) had low levels of preconception C3/C4. A triple aPL positivity was observed in 54 pregnancies, 14 of them were treated with combination therapy + HCQ. When considering the whole cohort, the addition of HCQ had not significantly improved the gestational outcome. Further stratification was performed on the basis of complement consumption. In the group of patients with preconception low C3/C4 levels the addition of HCQ had not significantly improved pregnancy outcome. We have lastly evaluated 40 pregnancies with a high-risk profile (triple aPL positivity and complement consumption), in which we have found that HCQ significantly improved gestational outcome (p=0.018, Table 1).Table 1.Relationship between APO, therapy during pregnancy and risk profile.All pregnancies (n=164)Reduced C3/C4 (n=58)Triple aPL+ and reduced C3/C4 (n=40)LDA+LMWH (n, %)LDA+LMWH+HCQ (n, %)pLDA+LMWH (n, %)LDA+LMWH+HCQpLDA+LMWHLDA+LMWH+HCQp(n, %)(n, %)(n, %)APO62 (46%)16 (53%)ns32 (68%)4 (36%)ns23 (77%)3 (30%)0.018No APO72 (54%)14 (47%)15 (32%)7 (64%)7 (23%)7 (70%)Total1343047113010This observation could not be confirmed in patients with single or double aPL positivity.ConclusionThe study shows that administering HCQ in addition to combination therapy can improve gestational outcome in aPL/PAPS high-risk patients. This observation confirms that HCQ exerts a beneficial effect on aPL pregnancies by complement inhibition as it was shown in animal models. In addition, our results provide the clinicians a useful tool to implement conventional treatment in patients at high risk of pregnancy complication or loss.References[1]De Carolis S, et al. Is there any role for the hydroxychloroquine (HCQ) in refractory obstetrical antiphospholipid syndrome (APS) treatment? Autoimmun Rev 2015;14:760-2.[2]Mekinian A, et al. The efficacy of hydroxychloroquine for obstetrical outcome in antiphospholipid syndrome: data from a European multicenter retrospective study. Autoimmun Rev 2015;40:498-502.[3]Mekinian A et al. Obstetrical APS: is there a place for hydroxychloroquine to improve the pregnancy outcome? Autoimmun Rev 2015;14:23-9.Disclosure of InterestsNone declared

BackgroundThe main goal for the management of rheumatoid arthritis (RA) is to control symptoms to reach clinical remission or low disease activity as the best possible alternative [1]. Although the number of available therapeutic options, a substantial proportion of patients remain symptomatic. Recent EULAR recommendations [2] shift focus to lifestyle interventions whose concurrent approach could help in controlling potential inflammatory triggers. In this context, olives and olive oil have beneficial properties on health mainly attributed to their high monounsaturated fatty acid content, and to the presence of phenolic compounds. To our knowledge, very few studies addressed the anti-inflammatory effects related to olives and olive oil consumption on RA disease activity.ObjectivesTo study the attitude of consumption of olives and olive oil in RA patients from northern Italy, and to assess the effect on disease activity.MethodsIn this observational cross-sectional study, all consecutive adult RA with disease duration ≥ 3 months were enrolled. Disease Activity Score on 28 joints (DAS28-CRP), Simple Disease Activity Index (SDAI) were recorded. Dietary habits in the previous six months were collected with a with a 110-item food frequency questionnaire. In this analysis, we focus on olive oil consumption with original response categories ranging from “never” to “more than 2 times per day” (in spoon units). We created a food group composed by olive oil, black and green olives (frequencies/day). Olive oil consumption was entered as the independent variable into multiple regression models. When disease activity was entered in continuous in the regression models, we estimated the effect on a 1-point increment/decrease in RA disease activity. When disease activity was modeled as a dichotomous variable, we estimated the odds ratios (ORs) of disease activity and the corresponding 95% confidence intervals (CIs) within unconditional multiple logistic regression models. We included in each model the potential confounding variables: age, sex, education, body mass index (BMI), cigarette smoking status, alcohol drinking intensity, disease duration, rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), and therapies.Results365 RA patients (median age: 58.46 years, 78.63% females) were included. Most of the patients (60.55%) finished the high school and/or the university. The median BMI was 23.63 (IQR: 21.00-26.78) Kg/m2; never smokers or drinkers were 51.64% and 29.04%, respectively. The median disease duration was 12.81 (IQR: 8.08-20.72) years, with RF positivity being 53.70% and ACPA positivity 50.96%. Disease activity measures DAS28-CRP and SDAI showed medians of 2.21 (IQR: 1.613.02) and 6.30 (IQR: 3.01-11.81), with high disease activity present in 3.84% and 5.75% of the sample, respectively. Major comorbidities included arterial hypertension (33.42%), gastro-esophageal reflux (19.18%), and gastritis (8.77%). After adjustment for the mentioned confounding factors, the ORs (and the corresponding 95% confidence interval) of RA disease activity was equal to 0.78 (95% CI: 0.76-1.31) for DAS28-CRP and to 0.76 (95% CI: 0.75-1.34) for SDAI, suggesting significant protection of about ~20% for both outcomes. Similarly, robust regression models for estimating the increment in the mean outcome disease activity scores, DAS28-CRP and SDAI in continuous, provided beta coefficients equal to -0.17 (Standard Error, SE: 0.06) with a p-value equal to 0.06 for DAS28-CRP and a beta coefficient of -1.13 (SE: 0.37) with a p-value equal to 0.04.ConclusionIncreasing frequency of consumption of a food group composed by olive oil, black and green olives is significantly associated to a lower risk of disease activity, as measured by both DAS28-CRP and SDAI, after adjustment for socio-demographic factors, therapy, disease duration and severity. Robust regression models allowed to quantify the mean reduction of DAS28-CRP in 0.17 points and that of SDAI in 1.13 points.References[1]Ann Rheum Dis 2020;79:685–699.[2]Ann Rheum Dis 2021;80:1278-1285AcknowledgementsThe authors thank the RANDIE study groupDisclosure of InterestsFrancesca Ingegnoli: None declared, Roberta De Vito: None declared, Roberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Galapagos, Lilly, Pfizer, Fresenius-Kabi, MSD, UCB, Roche,Janssen, Novartis, Sandoz, Consultant of: Abbvie, Amgen, BMS, Celltrion, Galapagos, Lilly, Pfizer, MSD, UCB, Janssen, Novartis, Sandoz, Maria Parpinel: None declared, Giuseppe Grosso: None declared, Monica Ferraroni: None declared, Valeria Edefonti: None declared

BackgroundThe ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire is a 29-item disease-specific PRO measure for AAV[1]. The Italian version of the AAV-PRO questionnaire (AAV-PRO_ita) was translated in collaboration with Oxford and Bristol University (UK) and was preliminarily tested on a single-center Italian cohort[2].ObjectivesThe main objective of this multicentric study was to assess the internal consistency, feasibility, and reliability of the AAV-PRO_ita in a large cohort of Italian AAV patients. The secondary objective was to investigate the clinical characteristics of AAV patients associated with AAV-PRO_ita domains.MethodsThe AAV-PRO_ita is describes the following disease domains: (1) organ-specific and systemic symptoms and signs (SSS); (2) physical function (PF); (3) social and emotional impact (SEI). In this study, Italian-speaking AAV patients were recruited from Italian Centres (N=13) with a large experience in the diagnosis and treatment of systemic vasculitis, belonging to the Vasculitis Study Group of the Italian Society of Rheumatology. Inclusion criteria were: a confirmed diagnosis of GPA, MPA, or EGPA; ANCA positivity in at least once occasion or biopsy-proven AAV; and age ≥18 years old. Participants completed the AAV-PRO_ita at three different time-points: baseline, after 5-7 days, and at month 3.Results229 AAV-patients (56.3% women) with a median age of 61 (IQR 51-72) were recruited and completed the questionnaires. The subtype of AAV was mainly GPA (131, 57.2%), followed by EGPA (58, 25.3%), and MPA (40, 17.5%). Median BVASv3 at baseline was 0 (IQR 0-3), whereas the median BVASv3 at the onset of disease was 14 (IQR 9-20). Participants had a median duration of disease of 67 (IQR 24-126) months. Patients who experienced at least one relapse, one hospitalization, and one severe infection were 40.2%, 53.3%, and 24%, respectively. 83% of the patients were on immunosuppressant therapy and 71.6% were still receiving glucocorticoids (GC).AAV-PRO_ita questionnaire had good internal consistency (Cronbach’s Alpha range 0.81-0.93) and good test-retest reliability (ICCs range 0.93-0.96). Item response rates were high overall (maximum 0.87% missing data), supporting the feasibility of the questionnaire.Concerning the domains of the questionnaire, female AAV patients scored higher (i.e. worse) in all three domains, especially in the SEI domain (p-value0.3, p-valueConclusionThe AAV-PRO_ita questionnaire is a new 29-item, disease-specific PRO measure for use in AAV in the Italian language. It is a self-administered Italian questionnaire with good internal consistency, feasibility, and reliability. AAV-PRO_ita proved to be a useful tool to explore the AAV patient’s perception of quality of life, and it could become an important way of measuring the unmet needs of AAV patients.References[1]Robson, J.C. et al. Validation of the ANCA-Associated Vasculitis Patient-Reported Outcomes (AAV-PRO) Questionnaire. Ann. Rheum. Dis.2018, 77, 1157–1164, doi:10.1136/annrheumdis-2017-212713.[2]Treppo, E.; Palese, A.; Vita, S.D.; Quartuccio, L. AB0392 PRELIMINARY VALIDATION OF THE ITALIAN VERSION OF ANCA-ASSOCIATED VASCULITIS PATIENT-REPORTED OUTCOME (AAV-PRO_ita) QUESTIONNAIRE: FATIGUE AND CHRONIC PAIN AS UNMET NEEDS BY CURRENT TREATMENTS. Ann. Rheum. Dis.2021, 80, 1224–1224, doi:10.1136/annrheumdis-2021-eular.2123.AcknowledgementsWe thank the Italian Study Group on Systemic Vasculitis.Disclosure of InterestsNone declared

BackgroundThe ongoing coronavirus disease 2019 (COVID-19) pandemic and subsequent waves still represent a healthcare issue. Their impact on the treat-to-target (T2T) strategy in rheumatoid arthritis (RA) patients has been seldom investigated. Difficult access to rheumatology outpatient clinic, laboratory and imaging investigations as well as nationwide containment measures could potentially affect disease activity and tight-control strategy. Recently, we reported how a telephone-based tight control strategy ensured satisfactory management of RA treated with targeted therapies during the first wave of the pandemic [1]. However, the performance of our different patterns of healthcare delivery across different pandemic waves has not been studied yet.ObjectivesTo analyze the impact of different patterns of healthcare delivery on remission of RA patients treated with targeted therapies during the first wave (2020) and second/third waves (2021) of pandemic compared to the pre-pandemic period (2019).MethodsIn this observational real-life study, data of our cohort of RA patients treated with biologic or targeted synthetic drugs were extracted from a longitudinal registry. Clinical Disease Activity Index (CDAI) was analyzed in the same period from 22nd of February to 18th of May for three consecutive years: before the pandemic (2019), during the first wave (2020), and during the second/third waves (2021). During the first wave, patients could choose whether to receive home drug delivery or to maintain their face-to-face visits, in the other periods only in-person visits were delivered. A generalized linear model with the binomial error was fitted to evaluate the difference in the proportion of patients in CDAI remission. Quantile regression was used to compare the median of CDAI in difficult-to-treat (D2T) patients [2]. In both models, the correlation of different measurements on the same patient was considered.ResultsIn the pre-pandemic period (2019), 407 RA patients were included in this study. During the first wave (2020) we analyzed 450 patients, of whom 359 patients chose in-person visits, while 91 patients home drug delivery and virtual visit. Finally, 540 patients were included in 2021 (second/third wave). The percentages of patients in CDAI remission were similar in the three periods (prevalence ratio 1.07, p-value 0.423 between 2020 and 2019, and 1.01, p-value 0.934 between 2021 and 2019). The CDAI remission rate was 40.55% (N=163), 43.18% (N=155) and 40.82% (N=220) in 2019, 2020 and 2021, respectively. The disease activity profile during the three periods is reported in detail in the Table 1 below. Among our cohort of D2T patients, the median value of CDAI before (2019), during the first wave (2020), and during the second/third wave (2021) changed significantly (p= 0.053 between 2020 and 2019 and p=0.006 between 2021 and 2019).Table 1.RA patientsCDAI201920202021No. missingN (%)No. missingN (%)No. missingN (%)Remission0163 (40.55%)89155 (43.18%)6220 (40.82%)Low0151 (37.56%)89140 (39.00%)6227 (42.12%)Moderate/ high088 (21.89%)8964 (17.83%)692 (17.07%)ConclusionAlthough the pandemic has imposed changes in our healthcare delivery, these different strategies seem to be effective in ensuring satisfactory management of RA treated with targeted therapies. The approaches modulated in the context of the different periods have been a feasible compensation for ensuring disease control even in D2T patients.References[1]Ann Rheum Dis 2021;80:1243-1245[2]Ann Rheum Dis 2021;80:31–5.Disclosure of InterestsAngela Flavia Luppino: None declared, Gilberto Cincinelli: None declared, Francesca Ingegnoli: None declared, Annalisa Orenti: None declared, Ennio Giulio Favalli Speakers bureau: Galapagos, BMS, Lilly, Pfizer, Novartis, Paid instructor for: Roche, MSD, Consultant of: AbbVie, Lilly, Galapagos, Janssen, Patrizia Boracchi: None declared, Roberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Galapagos, Lilly, Pfizer, Fresenius-Kabi, MSD, UCB, Roche,Janssen, Novartis, Sandoz, Consultant of: Abbvie, Amgen, BMS, Celltrion, Galapagos, Lilly, Pfizer, MSD, UCB, Janssen, Novartis, Sandoz.