Background The investigational drug sarilumab is a human monoclonal antibody directed against the interleukin 6 receptor.1 The phase 3 MOBILITY study (NCT01061736) examined sarilumab + methotrexate (MTX) vs placebo + MTX in a double-blind, 52-week, randomized trial of patients with active, moderate-to-severe rheumatoid arthritis (RA) with inadequate response to MTX.1 Both sarilumab doses (150 and 200 mg subcutaneously every 2 weeks [q2w]) demonstrated statistically significant improvements in signs and symptoms of RA, in physical function, and inhibition of radiographic progression. The most common treatment-emergent adverse events were infections, neutropenia, injection site reactions, and increased transaminases.
Objectives In the present study, radiographic efficacy of sarilumab across subpopulations from MOBILITY was assessed.
Methods To explore the consistency of radiographic response, treatment-by-subgroup interactions were assessed by rank ANCOVA for change in van der Heijde modified total Sharp score (mTSS) at week 52. A total of 19 subgroups were investigated (listed in Table footnote); those with P≤0.2 for interaction are presented. Radiographic progression was defined as mean change from baseline mTSS.
Results Both doses of sarilumab showed less progression relative to placebo across all subgroups. Change in mTSS across subgroups based on rheumatoid factor and anti–cyclic citrullinated peptide status and demographic characteristics such as age, sex, and ethnicity appeared to be consistent with overall study findings. Subgroups with interaction P≤0.2 were prior use of biologics and baseline C-reactive protein (CRP), body mass index (BMI), RA disease duration, median mTSS, and smoking history (Table). In some groups (lower BMI, no prior biologic use, higher baseline CRP, no history of smoking, and high mTSS), the treatment effect increased, because there was greater progression in the placebo group relative to the sarilumab groups. The progression with sarilumab 200 mg q2w was consistently lower compared with sarilumab 150 mg q2w. Progression was substantially greater in placebo patients with baseline mTSS >25 compared with those with baseline mTSS ≤25. These differences were not observed in sarilumab-treated patients. Joint space narrowing and erosion score showed patterns similar to the total score. Overall, sample sizes were limited in some subgroups.
Conclusions Sarilumab generally inhibited radiographic progression to a similar extent across a wide spectrum of subgroups. Nonetheless, the treatment effect appeared to be greater in subgroups with poor prognostic markers such as high levels of CRP and more structural damage at baseline, as well as in nonsmokers and patients with low BMI.
Genovese et al. Arthritis Rheumatol. 2015;67:1424–1437.
Acknowledgement This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Editorial assistance was provided by Rebecca Slager, PhD, MS, MedThink SciCom, and funded by Sanofi and Regeneron Pharmaceuticals, Inc.
Disclosure of Interest D. van der Heijde Consultant for: Sanofi, C. Fan Shareholder of: Sanofi, Employee of: Sanofi, H. van Hoogstraten Shareholder of: Sanofi, Consultant for: Sanofi, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. van Adelsberg Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, P. Miranda Grant/research support from: Sanofi, M. Genovese Grant/research support from: Roche, Sanofi, GSK, R-Pharma, RuiYi, and BMS, Consultant for: Roche, Sanofi, GSK, R-Pharma, RuiYi, and BMS