OP0028 Effects of Sarilumab plus MTX on Clinical, Radiographic, and Functional Endpoints in Patients with Moderate-To-Severe Rheumatoid Arthritis: Results of A Phase 3, Randomized, Double-Blind, Placebo-Controlled, International Study
Authors: M. Genovese, R.M. Fleischmann, A.J. Kivitz, M. Rell-Bakalarska, R. Martincova, S. Fiore, P. Rohane, H. van Hoogstraten, C. Fan, J. van Adelsberg, S. Weinstein, N. Graham, N. Stahl, G. Yancopoulos, T.W. Huizinga, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Sarilumab, a fully human mAb directed against IL-6R, demonstrated efficacy in phase 2 of SARIL-RA-MOBILITY in rheumatoid arthritis (RA) patients (pts) with inadequate response to methotrexate (MTX) and was generally well tolerated when dosed every other week (q2w). Two doses were chosen for phase 3. <h3>Objectives</h3> To evaluate the clinical efficacy, radiographic and functional improvement, and safety profile of subcutaneous dose regimens of sarilumab+MTX for the treatment of RA. <h3>Methods</h3> In phase 3 of the SARIL-RA-MOBILITY study, adults with active, moderate-to-severe RA who had an inadequate response to MTX were randomized to placebo (Pbo), sarilumab 150 mg q2w, or sarilumab 200 mg q2w (1:1:1) plus background MTX. The co-primary endpoints were: 1) proportion of pts achieving ACR20 response at Week (Wk) 24; 2) change from baseline in HAQ-DI at Wk 16 and; 3) change from baseline in van der Heijde modified total Sharp score (mTSS) at Wk 52. <h3>Results</h3> Baseline demographic and disease characteristics (efficacy population, n=1197) were similar across groups: 82% female; mean age 51 yrs; disease duration 9 yrs; RF+ 85%; tender joint count 26; swollen joint count 17; hsCRP 2.2 mg/dL. Both doses of sarilumab provided statistically significant, clinically meaningful improvement, relative to Pbo, in all three co-primary endpoints (Table). The key secondary endpoint, major clinical response, during the 52-wk study period, and all secondary clinical response endpoints, including proportion of ACR50 and ACR70 responses, reduction in DAS28CRP, and CDAI scores, were statistically significant with both sarilumab doses at Wk 24 and Wk 52. Treatment-emergent adverse events (AE) (safety population, n=1282) were observed in 62% of pts in Pbo and 75% to 78% in sarilumab groups. Forty serious AEs were reported in Pbo and 62 and 68 events in sarilumab 150 and 200 mg arms, respectively. The most frequently reported serious AEs were infections in 10, 11, and 17 pts in the Pbo, sarilumab 150 and 200 mg groups (3.9, 3.8 and 6.0 events/100 patient-years), respectively. Seven deaths occurred during the study with an onset of the fatal event during the double-blind period in 5 pts (2 Pbo, 2 150 mg, 1 200 mg) and during open label sarilumab rescue in 2 pts. Lab abnormalities included increases in lipids and transaminases and decreases in neutrophils. No serious infections occurred in pts with neutrophils &lt;1000/μL. <h3>Conclusions</h3> In this phase 3 study, both sarilumab doses (150 mg and 200 mg q2w), in combination with MTX, demonstrated efficacy in pts with active RA who had inadequate response to MTX. Both sarilumab doses met clinical, radiographic, and functional endpoints. Clinical response was maintained throughout the 52-wk study period. Infection SAEs and laboratory abnormalities with sarilumab are consistent with IL-6 signaling blockade. <h3>Acknowledgements</h3> Sponsored by Sanofi and Regeneron Pharmaceuticals Inc. (NCT01061736) <h3>Disclosure of Interest</h3> M. Genovese Grant/research support: Sanofi, Consultant for: Sanofi, R. Fleischmann Grant/research support: Sanofi, Regeneron Pharmaceuticals, Inc., Consultant for: Sanofi, Regeneron Pharmaceuticals, Inc., A. Kivitz Grant/research support: Sanofi, Regeneron Pharmaceuticals, Inc., M. Rell-Bakalarska: None declared, R. Martincova Shareholder of: Sanofi, Employee of: Sanofi, S. Fiore Shareholder of: Sanofi, Employee of: Sanofi, P. Rohane Shareholder of: Sanofi, Employee of: Sanofi, H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, C. Fan Shareholder of: Sanofi, Employee of: Sanofi, J. van Adelsberg Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., S. Weinstein Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., N. Graham Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., N. Stahl Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., G. Yancopoulos Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., T. Huizinga Consultant for: Sanofi, D. van der Heijde Consultant for: AbbVie, Amgen, AstraZeneca, Augurex, BMS, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Vertex, Employee of: Imaging Rheumatology bv <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3001