FRI0092 LONG-TERM SAFETY AND EFFICACY OF SARILUMAB OVER 5 YEARS IN PATIENTS WITH RHEUMATOID ARTHRITIS REFRACTORY TO TUMOR NECROSIS FACTOR INHIBITORS
Authors: R. Fleischmann, M. C. Genovese, K. Maslova, H. Leher, A. Praestgaard, G. R. Burmester
Journal: Annals of the Rheumatic Diseases (2020)

Background: Sarilumab is a human IL-6 receptor (IL-6R) inhibitor approved for the treatment of adults with moderate to severely active rheumatoid arthritis (RA). In the TARGET study ( NCT01709578 ), sarilumab plus conventional synthetic disease-modifying antirheumatic drugs (DMARDs) significantly improved signs and symptoms of RA and physical function versus placebo in patients refractory to tumor necrosis factor (TNF) inhibitors. Objectives: Here we report the long-term safety and efficacy of subcutaneous (SC) sarilumab over 5 years in patients who continued treatment in the open-label extension study (OLE), EXTEND ( NCT01146652 ). Methods: Patients who received double-blind placebo, sarilumab 150 mg, or sarilumab 200 mg every 2 weeks (q2w) in the 24-week randomized controlled trial (RCT) were eligible to receive open-label sarilumab 200 mg q2w in the OLE, with dose reduction to 150 mg q2w permitted to manage laboratory abnormalities or per investigator’s discretion. Safety outcomes are presented for the OLE population for the follow-up from RCT baseline through OLE cut-off date. Efficacy assessments included Clinical Disease Activity Index (CDAI) score and the proportion of responders (CDAI ≤10 and ≤2.8) over time. Results: Of the 546 patients randomized in the RCT, 454 (83%) entered and were treated with sarilumab 200 mg in the OLE (original placebo group n = 156; sarilumab 150 mg n = 145; sarilumab 200 mg n = 153). Demographics and disease characteristics at OLE baseline were similar across groups (mean age 53.2 years; 81% female; mean RA duration [SD] 11.8 years [8.9]). At the time of data cut-off (January 15, 2019), 199/546 (36%) patients had discontinued: 100 (18%), 68 (13%), and 27 (5%) due to treatment-emergent adverse events (AEs), other reasons, and lack of efficacy, respectively. Cumulative exposure to sarilumab through the RCT and OLE (n=521) was 1654.8 patient-years (PY), and 268 patients (51%) had ≥4 years’ exposure. The rates per 100 PY of AEs, serious AEs, AEs leading to discontinuation, and AEs leading to death were 160.4, 10.2, 8.1, and 0.3, respectively. The most common AEs were neutropenia and injection site erythema (15.3 and 11.9 per 100 PY). Absolute neutrophil count &lt;1000 cells/mm 3 (Grade 3–4 neutropenia) was observed in 74 patients (14.2%) and normalized on treatment in 48 (9.2%). Alanine aminotransferase &gt;3× the upper limit of normal was observed in 46 patients (8.8%) and normalized on treatment in 25 (4.8%). Infections and serious infections occurred at rates of 57.8 and 3.9 per 100 PY, respectively. Clinical efficacy was sustained through 5 years of the OLE (Table). At OLE Week 240 (n = 95) mean change (SD) in CDAI from RCT baseline was −31.2 (14.6). Table . Proportion of responders * Original RCT group Placebo +DMARD (n=156 ) Sarilumab 150 mg +DMARD (n=145 ) Sarilumab 200 mg +DMARD (n=153 ) CDAI ≤2.8, n (%) OLE baseline 21 (13) 26 (18) 23 (15) After 192 weeks’ follow-up 17 (11) 28 (19) 28 (18) CDAI ≤10, n (%) OLE baseline 62 (40) 75 (52) 76 (50) After 192 weeks’ follow-up 57 (37) 61 (42) 66 (43) *Nonresponder imputation Conclusion: The safety profile of sarilumab was consistent with results of Phase 3 trials, IL-6R inhibition, and SC administration, and no new safety signals were identified over 5 years of follow-up in patients with RA refractory to TNF inhibitors. Clinical efficacy was sustained through 5 years’ follow-up. Acknowledgments: Study funding and medical writing support (Joseph Hodgson, PhD, Adelphi Communications Ltd, Macclesfield, UK) provided by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. in accordance with GPP3 guidelines. Disclosure of Interests: Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme, Karina Maslova Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, Henry Leher Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., Amy Praestgaard Employee of: Sanofi Genzyme, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma