SAT0106 LONG-TERM SAFETY AND EFFICACY OF SARILUMAB OVER 5 YEARS IN PATIENTS WITH RHEUMATOID ARTHRITIS WITH 1 OR >1 PRIOR TUMOR NECROSIS FACTOR INHIBITOR FAILURES

• Published in: Annals of the rheumatic diseases Vol. 79; no. Suppl 1; p. 987
• Main Authors: Fleischmann, R., Genovese, M. C., Maslova, K., Leher, H., Praestgaard, A., Burmester, G. R.
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2020
• Subjects: Failure; Gastroesophageal reflux; Interleukin 6; Interleukin 6 receptors; Monoclonal antibodies; Necrosis; Patients; Pharmaceuticals; Rheumatoid arthritis; Safety; Stockholders; Tumor necrosis factor; Tumor necrosis factor-TNF; United States > US
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2020-eular.332

Background:A proportion of adult patients with rheumatoid arthritis (RA) are refractory to tumor necrosis factor inhibitors (TNFi), and treatment with subsequent biologics is commonly associated with reduced response. Sarilumab is a human IL-6 receptor inhibitor approved for the treatment of adults with moderate to severely active RA. In the Phase 3 TARGET study (NCT01709578), significant improvements in the signs and symptoms of RA and physical function were shown with sarilumab plus conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) versus placebo in patients refractory to TNFi.Objectives:To investigate long-term safety and efficacy of subcutaneous sarilumab over 5 years in patients with 1 or >1 TNFi treatment failure prior to their enrollment in TARGET, who continued onto the open-label extension (OLE) study, EXTEND (NCT01146652).Methods:In the 24-week randomized controlled trial (RCT), patients received placebo, sarilumab 150 mg, or sarilumab 200 mg every 2 weeks (q2w), and were eligible to receive open-label sarilumab 200 mg q2w in the OLE. Dose reduction to 150 mg q2w was permitted per investigator’s discretion, or to manage laboratory abnormalities. Safety outcomes are presented for the entire follow-up period from RCT baseline through the OLE. Efficacy was assessed using Clinical Disease Activity Index (CDAI) score.Results:Of the 546 patients randomized in the RCT, 454 (83%) entered the OLE, of whom 339 had 1 TNFi failure and 115 had >1 TNFi failure. Patients with >1 TNFi failure were older and had a longer duration of RA than patients with 1 TNFi failure (mean age [SD] 55.3 [12.6] and 52.5 [11.9] years, mean RA duration [SD] 13.9 [9.1] and 11.1 [8.8] years, respectively). Kaplan–Meier estimates of the probability of continuation at 5 years were similar between groups: 48% and 54% for patients with >1 and 1 TNFi failure, respectively. At the time of data cut-off (January 15, 2019) 199/546 patients (36%) had discontinued through the RCT and OLE. The rates per 100 patient-years of treatment-emergent adverse events (AEs) and AEs leading to discontinuation for patients with >1 and 1 TNFi failure were 290.6 and 197.9, and 6.5 and 8.1, respectively. Clinical efficacy of sarilumab was sustained in the OLE through 5 years in both groups, regardless of initial treatment in the RCT (Table).TableMean CDAI and proportion of CDAI respondersTreatment allocation in 24-week RCTPlacebo+DMARDSarilumab 150 mg+DMARDSarilumab 200 mg+DMARD(n=156)(n=145)(n=153)TNFi failures1>11>11>1CDAI, mean (SD)RCT baseline43.7 (12.7)42.5 (10.3)42.0 (13.0)44.3 (13.5)42.1 (13.5)48.5 (13.0)Change after 216 weeks’ follow-up−30.9 (17.5)−32.6 (15.2)−33.3 (15.8)−33.1 (12.7)−30.3 (13.6)−36.0 (18.1)CDAI ≤10, n (%)*OLE baseline48 (42)14 (33)59 (53)16 (47)56 (49)20 (51)After 216 weeks’ follow-up24 (21)10 (24)29 (26)7 (21)29 (25)8 (21)*Nonresponder imputationConclusion:The long-term safety and efficacy of sarilumab were similar in patients with 1 or >1 prior TNFi failure over 5 years’ follow-up. Clinical efficacy could be sustained through 5 years of treatment.Acknowledgments:Study funding and medical writing support (Joseph Hodgson, PhD, Adelphi Communications Ltd, Macclesfield, UK) provided by Sanofi Genzyme (Cambridge, MA, USA) and Regeneron Pharmaceuticals, Inc. (Tarrytown, NJ, USA) 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