SAT0125 LONG-TERM SAFETY WITH SARILUMAB PLUS CONVENTIONAL SYNTHETIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS AND SARILUMAB MONOTHERAPY IN RHEUMATOID ARTHRITIS: AN INTEGRATED ANALYSIS WITH 9,000 PATIENT-YEARS OF FOLLOW-UP

Abstract

Background Sarilumab, a human IL-6R blocker approved for the treatment of RA, has shown efficacy as monotherapy and in combination with csDMARDs in Phase 3 trials. Objectives We assessed long-term safety from the sarilumab clinical development program in adult patients with RA who received subcutaneous (SC) sarilumab in eight clinical trials and their open-label extensions: MOBILITY (NCT01061736), TARGET (NCT01709578), ASCERTAIN (NCT01768572), EASY (NCT02057250), COMPARE (NCT01764997), ACT11575 (NCT01217814), MONARCH (NCT02332590), ONE (NCT02121210), and the open-label extension EXTEND (NCT01146652). Methods Data (cut-off Jan 15, 2018) were pooled from patients on sarilumab+csDMARD (N=2887) or sarilumab monotherapy (N=471). Patients had received sarilumab 200 mg or 150 mg q2w SC, except for 151 patients from MOBILITY Part A who received 100 mg qw, 150 mg qw, or 100 mg q2w. Treatment-emergent (TE) adverse events (AEs), AEs of special interest (AESIs), and discontinuations were assessed. Results Demographics were similar between combination and monotherapy pools (mean age 52 years; 81–83% female), and 38.7% and 8.5% of patients had received prior bDMARDs. Cumulative drug exposure was 7,985.5 and 798.7 patient-years (PY), with maximum duration 7.3 and 3.5 years. Exposure-adjusted rates of TEAEs, serious AEs, and TEAEs leading to discontinuations were similar (Table). Infections were the most common AESI. Rates of serious infection were 3.7 and 1.0/100 PY for combination and monotherapy, respectively, and were not associated with decreased absolute neutrophil counts (ANCs). Incidences of ALT >3× upper limit of normal and ANC Conclusion The long-term safety profile of sarilumab, either as monotherapy (observed for >3.5 years) or with csDMARD (observed for >7 years), remains stable and consistent with the anticipated profile of an IL-6R blocker. Acknowledgement Study funding and editorial support (Helen Johns, Adelphi) were provided by Sanofi and Regeneron Pharmaceuticals, Inc. These data were previously presented at the 2018 American College of Rheumatology annual meeting. Disclosure of Interests Roy Fleischmann Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celtrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celtrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, Yong Lin Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, Gregory St John Shareholder of: Regeneron Pharmaceuticals Inc, Employee of: Regeneron Pharmaceuticals Inc, Desiree van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Union Chimique Belge, Chunfu Qiu Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, Juan Jose Gomez-Reino Grant/research support from: Biogen, Gilead, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, Consultant for: Biogen, Gilead, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, Jose Antonio Maldonado-Cocco Consultant for: Pfizer, Merck Sharp Dohme, Sanofi – Aventis, Novartis, Bristol Myers Squibb, Roche, Boehringer Ingelheim, Schering – Plough, Abbott, UCB, Eli Lilly, Gilead, Speakers bureau: Pfizer, Merck Sharp Dohme, Sanofi – Aventis, Novartis, Bristol Myers Squibb, Roche, Boehringer Ingelheim, Schering – Plough, Abbott, UCB, Eli Lilly., Marina Stanislav Consultant for: R-Pharm, Bruno Seriolo: None declared, Gerd Rudiger Burmester Consultant for: Roche, Sanofi-Genzyme, Speakers bureau: Roche, Sanofi-Genzyme