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SAT0185 Clinical and Radiographic Efficacy of Sarilumab Plus Methotrexate in Biologic-Experienced and Biologic-Naïve Patients with Rheumatoid Arthritis in a Phase 3, Randomized, Double-Blind, Placebo-Controlled International Study
  1. D. van der Heijde1,
  2. M.C. Genovese2,
  3. C. Fan3,
  4. S. Fiore3,
  5. D.L. Decktor4,
  6. R. Fleischmann5
  1. 1Leiden University Medical Centre, Leiden, Netherlands
  2. 2Stanford University Medical Center, Palo Alto
  3. 3Sanofi, Bridgewater
  4. 4Regeneron Pharmaceuticals, Inc, Tarrytown
  5. 5Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, United States

Abstract

Background The efficacy and safety of sarilumab, a fully human monoclonal antibody directed against IL-6R, has been shown in patients with moderate-to-severe rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX) in the randomized, double-blind, placebo (Pbo)-controlled, phase 3 part of the MOBILITY study (NCT01061736).1 Approximately 20% of patients were exposed to biologic DMARDs (bDMARDs), defined as prior use of a non-investigational biologic DMARD for RA. Of these, 50% had received prior anti-TNF therapy and none had stopped bDMARD treatment due to lack of efficacy. The clinical efficacy and safety of sarilumab in bDMARD-experienced and -naïve MOBILITY patients was previously reported.2

Objectives To compare the clinical and radiographic efficacy and safety of sarilumab vs Pbo at 52 weeks in RA patients who were bDMARD-experienced (including prior anti-TNF therapy) and bDMARD-naïve in MOBILITY.

Methods This post hoc analysis of MOBILITY evaluates sarilumab clinical and radiographic efficacy and safety over 52 weeks in the intention-to-treat population, categorized according to prior bDMARD exposure, including a subset of patients with prior anti-TNF therapy.

Results Compared with placebo, smaller numerical mean increases in mTSS, including erosion (ES) and joint space narrowing (JSN), were observed with sarilumab (150 mg + MTX and 200 mg q2w + MTX), at Wks 24 and 52, irrespective of prior bDMARD use (including the prior anti-TNF therapy subgroup). For each group, a significantly greater percentage of patients receiving sarilumab had no radiographic progression at Wk 52 vs Pbo and, for patients with radiographic progression, the cumulative probability distribution plots for ΔTSS, ΔES and ΔJSN (from baseline) showed a frequency distribution favorable to sarilumab (both doses). In both bDMARD-experienced and -naïve RA patients, each of the sarilumab doses + MTX resulted in clinically meaningful and statistically significant ACR20, ACR50, ACR70, CDAI and DAS28-CRP responses vs Pbo at Wk 24; similar results were observed for the prior anti-TNF therapy subset. ACR20, 50 and 70 responses were maintained in bDMARD-experienced and -naïve subgroups up to Wk 52. The most common treatment-emergent adverse events with sarilumab + MTX included infections, neutropenia, injection site reactions and increased transaminases, irrespective of prior bDMARD experience.

Conclusions These results suggest that, irrespective of prior bDMARD experience, sarilumab improved signs and symptoms of RA and inhibited progression of structural damage in patients with active RA and inadequate response to MTX.

References

  1. Genovese M et al. Abstr. No. EULAR14-SCIE-3001 presented at EULAR 2014, Paris, France

  2. Fleischmann R et al. Arthritis Rheumatol 2014; 66(11) Abstr 2823:S1232–3

Acknowledgements 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.

Disclosure of Interest D. van der Heijde: None declared, M. Genovese Grant/research support from: Sanofi, Regeneron, Eli Lilly, Consultant for: Sanofi, Regeneron, Eli Lilly, C. Fan Shareholder of: Sanofi, Employee of: Sanofi, S. Fiore Shareholder of: Sanofi, Employee of: Sanofi, D. Decktor Shareholder of: Johnson & Johnson, Employee of: Regeneron, 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

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