LAUSR

Background: Long-term data are being collected on sarilumab in combination with csDMARDs in patients with RA originally enrolled in six trials (TARGET, NCT01709578; MOBILITY, NCT01061736; NCT01764997; NCT01768572; NCT02057250; NCT01217814) including those who continued into extension trials. Objectives: To assess efficacy and safety of long-term treatment with sarilumab plus csDMARDs in patients with RA. Methods: Long-term efficacy and safety data were available in patients enrolled in placebo-controlled trials of sarilumab 150 or 200 mg sc q2w who continued into the open-label EXTEND trial of sarilumab 200 or 150 mg sc q2w (NCT01146652). Safety data were evaluated in 2887 patients who received ≥1 dose of sarilumab sc in combination with csDMARDs. Results: Clinical and radiographic efficacy of sarilumab plus csDMARDs was maintained over 5 years’ follow-up (table 1; figure 1). Initial treatment with either dose of sarilumab was associated with significantly better radiographic outcome than placebo. Initial treatment with sarilumab 200 mg portended better radiographic outcome than sarilumab 150 mg or placebo. Mean duration of sarilumab treatment in the safety population was 2.6 years (max 6.8), representing 7412 cumulative patient-years of exposure. Incidence rate of adverse events of special interest (AESIs; table 2) was generally stable over >5 years' treatment, with no signal for increased rate of any AESI (including serious AEs and serious infection) over time. Incidences of injection site reaction, ANC <1 Giga/L, & elevated ALT declined over time.Table 1 Clinical response, % (number of patients assessed) DAS28-CRP<2.6 (remission) CDAI ≤2.8 (remission) Initial treatment MOBILITY (52 weeks)→EXTEND Week 148 196 244 148 196 244 Placebo 58.6 (249) 59.3 (231) 63.8 (207) 28.1 (249) 32.9 (231) 36.4 (209) Sarilumab 150 mg 61.9 (239) 63.0 (219) 63.1 (195) 30.5 (239) 32.6 (221) 34.2 (199) Sarilumab 200 mg 67.5 (237) 65.3 (225) 70.7 (208) 36.6 (238) 36.7 (226) 39.8 (211) TARGET (24 weeks)→EXTEND Week 48 96 144 48 96 144 Placebo 38.1 (139) 39.3 (122) 41.0 (117) 15.9 (138) 19.5 (123) 17.2 (116) Sarilumab 150 mg 44.9 (136) 49.1 (116) 53.8 (104) 18.1 (138) 22.4 (116) 23.4 (107) Sarilumab 200 mg 41.4 (140) 49.2 (126) 53.5 (114) 15.7 (140) 23.0 (126) 24.3 (115)Table 2 Treatment emergent adverse event rates per 100 patient-years Any AE/SAE 147/9.6 AE leading to death/discontinuation 0.4/9.1 AEs of special interest Infections (all/serious/opportunistic/TB) 54.7/3.7/0.9/0.1 Injection site reactions 24.9 Hypersensitivity reaction 5.6 Malignancy (all/excluding NMSC) 0.7/0.5 MACE (primary/narrow) 0.4/0.5 Medically adjudicated GI perforation 0.1 Lupus-like syndrome 0.1 Figure 1 Change in mTSS in patients who completed 52-week double-blind MOBILITY study and subsequently entered open-label EXTEND study Conclusions: Clinical efficacy and inhibition of progression of structural damage with sarilumab plus csDMARDs was sustained up to 5 years of follow-up in patients with diverse prior pharmacologic therapies. The safety profile of sarilumab plus csDMARDs remained stable over >5 years’ treatment. Acknowledgements: Study sponsored by Sanofi and Regeneron Pharmaceuticals, Inc, who funded medical writing support by Matt Lewis, Adelphi Group Disclosure of Interest: G. R. Burmester Grant/research support from: AbbVie, Pfizer, UCB, Roche, Consultant for: AbbVie, Lilly, Merck Sharpe & Dohme, Pfizer, Sanofi, Roche, UCB, Speakers bureau: AbbVie, Lilly, Merck Sharpe & Dohme, Pfizer, Sanofi, Roche, UCB, Y. Lin Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, G. St John Shareholder of: Regeneron, Employee of: Regeneron, S. Wang Employee of: Sanofi, J. J. Gomez-Reino Grant/research support from: Roche, Merck Sharpe & Dohme, Consultant for: Biogen, Gilead, Lilly, Merck Sharpe & Dohme, Pfizer, Speakers bureau: Bristol-Myers Squibb, Janssen and Janssen, Merck Sharpe & Dohme, Pfizer, Roche, Sandoz, J. A. Maldonado-Cocco Consultant for: Pfizer, Merck Sharpe & Dohme, Sanofi-Aventis, Novartis, Bristol-Myers Squibb, Roche, Boehringer Ingelheim, Schering-Plough, Abbott, UCB, Eli Lilly, Gilead, Speakers bureau: Pfizer, Merck Sharpe & Dohme, Sanofi-Aventis, Novartis, Bristol-Myers Squibb, Roche, Boehringer Ingelheim, Schering-Plough, Abbott, UCB, Eli Lilly, Gilead, J. C. Salazar Grant/research support from: Pfizer, Abbvie, Consultant for: Glaxo, Pfizer, Abbvie, UCB, Janssen, Speakers bureau: Roche, Abbvie, Janssen, D. van der Heijde Shareholder of: Imaging Rheumatology bv., 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, UCB, M. C. Genovese Grant/research support from: Sanofi/Genzyme, Genentech/Roche, RPharm, Consultant for: Sanofi/Genzyme, Genentech/Roche, RPharm