FRI0186 Impact of Concomitant Methotrexate Dose on the Efficacy and Safety of Sarilumab for Treatment of Moderate-to-Severe Rheumatoid Arthritis: The Mobility Study
Authors: T.W.J. Huizinga, Y. Yazici, D. Thompson, D.L. Decktor, C. Fan, R. Fleischmann
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Methotrexate (MTX) is the most commonly used conventional synthetic DMARD (csDMARD) for the treatment of rheumatoid arthritis (RA). In the phase 3 MOBILITY study (NCT01061736),<sup>1</sup> of sarilumab in inadequate responders to MTX, MTX was continued at the dose prescribed at screening, which was assumed to be the maximally tolerated dose. This sub-analysis evaluates whether the different doses of MTX, in association with sarilumab, had an effect on efficacy or safety outcomes in MOBILITY. <h3>Objectives</h3> To explore the relationship of MTX dose on the efficacy or safety of sarilumab in the treatment of active RA in MTX-IR patients. <h3>Methods</h3> The MOBILITY study design and methods have been reported.<sup>2</sup> Patients were required to be on a stable dose of MTX of 10–25 mg/wk for at least 6 weeks, except for Asian-Pacific region patients (6–25 mg/wk) prior to enrolment and to maintain this dose throughout the trial. A sufficient number of subjects with doses of 7.5-25 mg/wk were included: 11 (0.92%) patients were excluded from the analysis due to small numbers receiving doses of &lt;7.5 and &gt;25mg/wk. The relationship between efficacy and safety outcomes for sarilumab and MTX was assessed by appropriate regression models (logistic or generalized linear) in this post hoc analysis. <h3>Results</h3> 1186 patients were included. For each dose group in each treatment arm we computed proportions of ACR20 responders at Wk 24 and 52; no apparent difference in achieving an ACR20 response was observed with increasing MTX dose in any treatment group (Figure). A logistic regression assessment confirms this observation: for sarilumab 150 mg and 200 mg. Based on mean change from baseline in HAQ-DI at Wk 24, no apparent relationship with MTX dose was observed. A linear regression model assessment provides confirmation of the results. There was no statistical difference in mean HAQ-DI change from baseline based on MTX dose in the Pbo, sarilumab 150 mg or sarilumab 200 mg groups. Similar findings were observed for changes from baseline for DAS28-CRP, FACIT-Fatigue, and mTSS (change and progression). There was no association of the incidence of treatment-emergent adverse events (AE), serious AEs and changes in ALT, neutrophil counts and lipids with increasing MTX doses. <h3>Conclusions</h3> In this post hoc analysis, within the sarilumab 150 mg or sarilumab 200 mg dose groups, efficacy or safety was similar across concomitant MTX doses. <h3>References</h3> Genovese M et al. Abstr. No. EULAR14-SCIE-3001 presented at EULAR 2014, Paris, France Kavanaugh A et al. Abstr. No. 2824 presented at ACR 2014, Boston, MA, USA <h3>Acknowledgements</h3> The study was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Editorial support was provided by Diane Davies of Envision Scientific Solutions and was funded by Sanofi and Regeneron Pharmaceuticals Inc. <h3>Disclosure of Interest</h3> T. Huizinga Consultant for: Merck, UCB, BMS, Biotest AG, Pfizer, Novartis, Roche, Sanofi, Abbott, Crescendo Bioscience, Nycomed, Boeringher Ingelheim, Takeda, Zydus, and Eli Lilly, Y. Yazici Shareholder of: Samumed, Grant/research support from: BMS, Celgene, Genentech, Consultant for: BMS, Celgene, Employee of: Samumed, D. Thompson Shareholder of: Regeneron, Employee of: Regeneron, D. Decktor Shareholder of: Johnson &amp; Johnson, Employee of: Regeneron, C. Fan Shareholder of: Sanofi, Employee of: Sanofi, R. Fleischmann Grant/research support from: AbbVie, Amgen, Ardea, AstraZeneca, BMS, Celgene, GSK, Janssen, Eli Lilly, Merck, Pfizer, Resolve, Roche, Sanofi, UCB, Consultant for: AbbVie, Akros, Amgen, Antares, Ardea, AstraZeneca, Augurex, BMS, Celgene, Covagen, Five Prime, GSK, Iroko, Janssen, Eli Lilly, McNeil, Merck, Pfizer, Plexxicon, Resolve, Roche, Sanofi, Teva, UCB, Vertex