THU0217 Similar efficacy and safety of sarilumab 150 mg or 200 mg q2w regardless of primary (1°) or secondary (2°) failure with tnf inhibitors
Authors: R. Fleischmann, A. Spindler, A. Kivitz, D. Ching, E.K. Mangan, T. Kimura, M. Iglesias-Rodriguez, G.R. Burmester
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Sarilumab (150 or 200 mg subcutaneously [SC] every 2 wks [q2w])+csDMARDs demonstrated efficacy in adults with moderate–to-severely active rheumatoid arthritis (RA) with intolerance or inadequate response to prior TNFi treatment in TARGET (NCT01709578). Patients with an initial refractory response (1° failure) to TNFi may respond differently to subsequent treatment vs those who initially respond but lose TNFi effectiveness (2° failure). <h3>Objectives</h3> This post hoc analysis examined efficacy and safety of sarilumab +csDMARDS in patients who had previously demonstrated 1° vs 2° TNFi failure. <h3>Methods</h3> TNFi failure (1° vs 2°) was investigator-determined on enrolment to TARGET. Patients who experienced 1° or 2° failure were randomised to placebo (pbo; n=75 and n=99), sarilumab 150 mg (n=72; n=91), or sarilumab 200 mg q2w (n=64; n=103), respectively. Disease activity, physical function (HAQ-DI), and safety were assessed at Wk 24. <h3>Results</h3> By Wk 24, ACR20/50/70 response rates and improvements in LS mean HAQ-DI were similar in both sarilumab dose groups and superior to pbo, irrespective of 1° vs 2° TNFi failure (table 1). Odds ratios for the benefit of sarilumab over pbo according to ACR response rates, HAQ-DI, DAS28-CRP, CDAI and SDAI (figure 1) showed no differences between patients with 1° vs 2° failures. No significant treatment by subgroup (1° vs 2° failure) interactions were observed. In the 1° failure group, treatment emergent adverse events (TEAEs; table 1) occurred in 59.7%, 65.6% vs 45.3% (sarilumab 150, 200 mg vs pbo, respectively) of patients; and in 73.6% and 63.1% vs 52.5% with sarilumab 150, 200 mg vs pbo, respectively, in the 2° failure group. There was only one TEAE leading to death (pbo group) and one case each of venous thrombosis (200 mg sarilumab q2w, 2°) and pulmonary embolism (150 mg sarilumab q2w, 2°). <h3>Conclusions</h3> Key efficacy and safety measures were similar in patients treated with sarilumab +csDMARDs, regardless of previous 1° or 2° failure with TNFis. <h3>Acknowledgements</h3> Study funding and medical writing support (Vicki Cronin, Adelphi) provided by Sanofi and Regeneron Pharmaceuticals, Inc. <h3>Disclosure of Interest</h3> R. Fleischmann Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, EMD-Serono, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi-Genzyme, UCB, Consultant for: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, GSK, Eli Lilly, Novartis, Pfizer, Sanofi-Genzyme, UCB, A. Spindler: None declared, A. Kivitz Shareholder of: Novartis, Consultant for: AbbVie, Janssen, Pfizer, UCB, Genzyme, Sanofi, Regeneron, Boehringer Ingelheim, Sun Pharma, Speakers bureau: Celgene, Genentech, Merck, Novartis, Pfizer, Genzyme, Sanofi, Regeneron, Horizon, D. Ching Grant/research support from: Sanofi, Lilly, Celgene, Pfizer, Galapagos, Gilead and Abbvie, Consultant for: Abbvie, E. Mangan Shareholder of: Regeneron, Pfizer, Employee of: Regeneron, T. Kimura Shareholder of: Regeneron, Employee of: Regeneron, M. Iglesias-Rodriguez Employee of: Sanofi, G. Burmester Grant/research support from: AbbVie, Pfizer, UCB, Roche, Consultant for: AbbVie, Lilly, Merck Sharpe and Dohme, Pfizer, Sanofi, Roche, UCB, Speakers bureau: AbbVie, Lilly, Merck Sharpe and Dohme, Pfizer, Sanofi, Roche, UCB