Background Sarilumab, an investigational human IL-6 receptor mAb, demonstrated statistically significant improvements in signs and symptoms of RA, physical function, and inhibition of radiographic progression in combination with MTX in the 1-year phase 3 MOBILITY study (NCT01061736).
Objectives This analysis examined 2-year clinical and radiographic outcomes and safety in patients completing the MOBILITY study who continued in the open-label, long-term extension (OLE) study EXTEND (NCT01146652) and were treated with sarilumab 200 mg q2w.
Methods Patients who participated in MOBILITY were initially randomized to placebo or sarilumab 150 or 200 mg subcutaneously for up to 1 year. Early rescue with open-label sarilumab 200 mg was allowed in case of insufficient response after wk 16. Following MOBILITY patients were eligible for enrollment in EXTEND, where all patients received active treatment (sarilumab 200 mg q2w after final dose selection) + MTX. Radiographs of patients who had a radiograph available at baseline and in the first and second year were centrally read by 2 readers independently. Linear extrapolation was performed if a patient had 2 postbaseline radiographs but was missing a radiograph at year 2. Analysis of clinical endpoints was based on all available data. Clinical endpoints were set to missing after early treatment discontinuation but not after rescue with open-label sarilumab. Statistical analysis was performed on the basis of patients' original randomized treatment assignment (placebo, or sarilumab 150 or 200 mg), regardless of whether the patient was rescued during the double-blind period (MOBILITY).
Results Of the 1197 randomized patients enrolled in MOBILITY, 901 patients participated in EXTEND (Table). At year 2, disease activity (DAS28-CRP and CDAI) reached the same level regardless of initial treatment. In addition, at year 2, percentages of patients achieving DAS28-CRP <2.6 were similar in the 3 groups, and similar trends were observed for CDAI remission (CDAI ≤2.8) (Table). Two-year radiographic data were available for 800 patients; linear extrapolation was used in 56 of these patients. mTSS scores at year 1 in initial placebo and sarilumab 150 and 200 mg groups were maintained through year 2 in the OLE (Table). TEAEs occurred in 86.3% of patients over 2 years, and SAEs occurred in 16.3% of patients. Over 2 years, death occurred in 7 patients (0.6%). Five deaths were classified as unrelated to treatment. Two deaths were assessed as possibly associated with sarilumab (streptococcal sepsis, possible stroke). The most common TEAEs (≥5% in ≥1 treatment group) were neutropenia (17.8%), increased ALT (11.6%), and upper respiratory tract infections (11.1%).
Conclusions Once active treatment with sarilumab 200 mg q2w was initiated after year 1, clinical response at year 2 was similar irrespective of prior treatment, and radiographic progression stabilized. Adverse events were consistent with the anticipated effects of IL-6 inhibition and the known safety profile of sarilumab.
Acknowledgement This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Editorial assistance was provided by Andrea Eckhart, PhD, MedThink SciCom, and funded by Sanofi and Regeneron Pharmaceuticals, Inc.
Disclosure of Interest D. van der Heijde Consultant for: Sanofi, J. van Adelsberg Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. Fay Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, N. Graham Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, C. Fan Shareholder of: Sanofi, Employee of: Sanofi, A. Spindler: None declared, M. Genovese Grant/research support from: Roche, Sanofi, GSK, R-Pharma, RuiYi, and Bristol-Myers Squibb, Consultant for: Roche, Sanofi, GSK, R-Pharma, RuiYi, and Bristol-Myers Squibb