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
Authors: Roy Fleischmann, Yong Lin, Gregory St John, Désirée van der Heijde, Chunfu Qiu, Juan Jose Gomez-Reino, Jose Antonio Maldonado-Cocco, Marina Stanislav, Bruno Seriolo, Gerd Rüdiger Burmester
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> 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. <h3>Objectives</h3> 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). <h3>Methods</h3> 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. <h3>Results</h3> 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 &gt;3× upper limit of normal and ANC &lt;1.0 giga/L were 10.3% and 12.7% for combination, respectively, and 5.5% and 14.9% for monotherapy. Rates of confirmed GI perforation for combination and monotherapy were 0.1 and 0/100 PY. Analyzing data by 6-month intervals showed no increase in rate over time for serious infections, malignancy, major adverse cardiac events, or ANC &lt;1.0 giga/L. <h3>Conclusion</h3> The long-term safety profile of sarilumab, either as monotherapy (observed for &gt;3.5 years) or with csDMARD (observed for &gt;7 years), remains stable and consistent with the anticipated profile of an IL-6R blocker. <h3>Acknowledgement</h3> 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. <h3>Disclosure of Interests</h3> 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, Désirée 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 &amp; Dohme, Pfizer, Roche, Consultant for: Biogen, Gilead, Eli Lilly, Merck Sharp &amp; 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 Rüdiger Burmester Consultant for: Roche, Sanofi-Genzyme, Speakers bureau: Roche, Sanofi-Genzyme