Background/Purpose: Sarilumab is a human mAb blocking the IL-6Rα. Sarilumab + MTX demonstrated significant improvements in RA signs and symptoms, physical function, and inhibition of radiographic progression in the 1-year phase 3 MOBILITY study (NCT01061736). This analysis examined 3-year clinical and radiographic outcomes and safety in patients who completed MOBILITY and entered the open-label extension (OLE) study EXTEND (NCT01146652).

Methods: Patients in MOBILITY were initially randomized to placebo or sarilumab 150 or 200 mg every 2 weeks (q2w) subcutaneously for up to 1 year. Early rescue with open-label sarilumab 200 mg q2w was allowed for insufficient response after week 16. After completion of MOBILITY, patients were eligible for enrollment in EXTEND, in which all patients received active treatment (sarilumab 200 mg q2w after final dose selection) + MTX. DAS28-CRP and clinical disease activity index (CDAI) assessed clinical efficacy. Radiographs from patients at baseline and subsequent second and third years were centrally read by 2 readers independently. Linear extrapolation was applied at year 3 for patients who had data at year 2 and from an unscheduled visit between years 2 and 3 but not at year 3. Statistical analysis at year 3 was performed on the basis of patients’ original randomized treatment assignment, regardless of whether they were rescued during the double-blind period (MOBILITY).

Results: Of the 1197 randomized patients in MOBILITY, 901 participated in EXTEND (Table). At year 3, after all patients had received open-label sarilumab for 2 years, percentages of patients achieving DAS28-CRP <2.6 or CDAI ≤2.8 were similar in patients originally treated with either dose of sarilumab or placebo, though the initial sarilumab 200 mg group exhibited the most favorable outcomes (Table). Improvements were maintained within each group from year 2 to year 3. Three-year radiographic data were available for 755 patients; linear extrapolation was used in 29. Modified total Sharp scores at year 3 in the initial placebo and sarilumab 150 and 200 mg groups were only slightly increased since year 2 (Table). Treatment-emergent adverse events (TEAEs) occurred in 89.7% of patients over 3 years. The most common TEAEs (≥10%) were neutropenia (19.4%), increased alanine aminotransferase (13.0%), and upper respiratory tract infections (12.7%). Infections were the most frequently reported serious AE (4.2/100 patient-years).

Conclusion: Active treatment with sarilumab 200 mg q2w resulted in durable clinical response and stabilization of radiographic progression at 3 years irrespective of prior treatment, though the initial sarilumab 200 mg group showed the most favorable outcomes. Adverse events were consistent with the anticipated effects of IL-6 inhibition and the known safety profile of sarilumab.