Background In patients with rheumatoid arthritis (RA), prolonged disease duration at treatment initiation has been associated with unfavourable outcomes.1 Sarilumab 150 mg or 200 mg sc q2w plus methotrexate (MTX) has demonstrated efficacy vs placebo (Pbo) in the phase 3 MOBILITY study in patients with active RA and inadequate response to MTX.
Objectives To evaluate the clinical and radiographic efficacy of sarilumab in patients from MOBILITY with RA duration of ≤3 and >3 yrs (NCT01061736).
Methods The study design and methods for MOBILITY have previously been presented.2 This prespecified analysis provides radiographic and clinical efficacy results by RA duration from diagnosis to baseline (≤3 vs >3 yrs) in the intent-to-treat population.
Results In MOBILITY, mean RA duration was 9.03±7.85 yrs (range, 0.3–44.7 yrs). 308 patients, ≤3 yrs (Pbo, n=103; sarilumab 150 mg, n=107; sarilumab 200 mg, n=98); 889 patients, >3yrs (Pbo, n=295; sarilumab 150 mg, n=293; sarilumab 200 mg, n=301). Baseline differences were noted for RA duration (mean 1.35 vs 11.7 yrs; ≤3 vs >3 yrs), age (mean age 47 vs 51.9 yrs, ≤3 vs >3 yrs), and mTSS (range 13.8–19.2 vs 57.3–66.7; ≤3 vs >3 yrs). ACR20 responses were numerically higher with sarilumab vs Pbo, irrespective of RA duration (Table). Similar trends were seen for ACR50 and ACR 70 responses. In the Pbo group, substantially lower ACR50 and ACR70 response rates were observed in those with RA duration of >3 yrs vs ≤3 yrs. At Wk 16, HAQ-DI improvements were numerically greater with sarilumab in both RA duration groups vs Pbo. In both groups, less disease progression (reflected in Wk 52 mTSS scores) was observed with sarilumab vs Pbo. No radiographic progression was observed in a greater percent of patients on sarilumab 200 mg vs Pbo (≤3 yrs: 65.3% sarilumab 200 mg vs 41.7% Pbo [p=0.0007]; >3 yrs: 52.5% sarilumab 200 mg vs 37.6% Pbo [p=0.0003]). Frequencies of treatment-emergent and serious adverse events (AEs) were comparable across patient subsets. The most frequent AEs in both groups were infections. Laboratory abnormalities were more frequent with sarilumab treatment and included increases in transaminases and decreases in neutrophils. Four of the 5 deaths in the study occurred in groups with RA >3 yrs.
Conclusions In this analysis, the subgroups receiving sarilumab had improvements in signs and symptoms of RA, physical function, and decreased progression of structural joint damage. With sarilumab 150 mg, most responses were similar, regardless of RA duration. With sarilumab 200 mg, a greater magnitude of responses was observed in the group with RA <3 yrs. Frequency of AEs did not differ by disease duration.
Anderson JJ et al. Arthritis Rheum. 2000;43:22–9
Kavanaugh A et al. Abstr. No. 2824 presented at ACR 2014, Boston, MA, USA
Acknowledgements The study was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Editorial support was provided by Tara Miller of Envision Scientific Solutions and was funded by Sanofi and Regeneron Pharmaceuticals Inc.
Disclosure of Interest P. Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche Takeda, UCB, D. Decktor Shareholder of: Johnson & Johnson, Employee of: Regeneron, D. Nguyen Shareholder of: AbbVie, Employee of: Sanofi, C. Fan Shareholder of: Sanofi, Employee of: Sanofi, A. Kavanaugh Grant/research support from: Sanofi