Sarilumab Plus Methotrexate in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results of a Phase III Study

Abstract

Objective To evaluate the efficacy and safety of sarilumab in combination with methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). Methods Adults with moderate‐to‐severe RA and an inadequate response to MTX were randomized (1:1:1) to receive sarilumab (doses of 150 mg or 200 mg) or placebo every 2 weeks in conjunction with weekly MTX for 52 weeks. Co–primary end points were the proportion of patients achieving American College of Rheumatology 20% (ACR20) improvement responses at week 24, change from baseline in the Health Assessment Questionnaire (HAQ) disability index (DI) at week 16, and change from baseline in the modified Sharp/van der Heijde score (SHS) of radiographic damage at week 52. Results Baseline characteristics were similar among the groups. For all 3 co–primary end points, the sarilumab 150 mg and 200 mg groups demonstrated statistically significant improvements as compared with the placebo group (ACR20 response rate at week 24, 58.0%, 66.4%, and 33.4%, respectively [P < 0.0001]; least squares mean change in HAQ DI at week 16, −0.53, −0.55, and −0.29, respectively [P < 0.0001]; and mean change in SHS at week 52, 0.90, 0.25, and 2.78, respectively [P < 0.0001]). The most common treatment‐emergent adverse event was infection. In the sarilumab 150 mg, sarilumab 200 mg, and placebo groups, the incidence of serious infections was 2.6%, 4.0%, and 2.3%, respectively. Elevations in alanine aminotransferase levels >3‐fold the upper limit of normal occurred in 9.5%, 8.0%, and 2.1% of patients, respectively; in 24 patients, this led to discontinuation of treatment. Elevated total cholesterol levels were observed in 36.8%, 43.0%, and 18.3% of patients, respectively. In patients receiving 150 mg and 200 mg sarilumab, neutrophil counts of 0.5 to <1.0 × 109/liter were observed in 5.1% and 7.8% of patients, respectively, while neutrophil counts of <0.5 × 109/liter were observed in 0.9% and 0.7% of patients, respectively; none of the patients receiving placebo experienced changes in neutrophil counts. Conclusion In RA patients treated with sarilumab (150 mg or 200 mg every 2 weeks) in combination with MTX, both doses provided sustained clinical efficacy, as shown by significant improvements in symptomatic, functional, and radiographic outcomes. Sarilumab was generally well tolerated. The adverse events observed in this study were consistent with the effects of interleukin‐6 signaling blockade.

Sarilumab: a new IL‐6 receptor blocker for rheumatoid arthritis

“…4 6 The MOBILITY trial ran domised 1197 patients with moderate to severe active rheumatoid arthritis despite treatment with methotrexate to receive methotrexate plus sarilumab 150mg or 200mg fortnightly or methotrexate plus placebo. 4 Patients who had previously not responded to treatment with a biolog ical DMARD were excluded. The primary endpoints were the ACR20 response (the proportion of patients meeting American College of Rheumatology criteria for 20% improvement in disease activity) after 24 weeks; change in physical function measured by the Health Assessment Questionnaire disability index after 16 weeks; and change in radiographic joint damage at week 52.…”

Anti-interleukin and associated receptors monoclonal antibodies therapy in autoimmune diseases

“…Analogous to the other IL-6 signaling blockers, the most common AE was infections. In a recently phase 3 study, efficiency and safety of sarilumab in combination with MTX in RA patients were evaluated [41] . That study has been used sarilumab with the dose of 150 mg or 200 mg every 2 weeks.…”

Usability and Patient Preference Phase 3 Study of the Sarilumab Pen in Patients with Active Moderate-to-Severe Rheumatoid Arthritis

“…Blockade of interleukin 6 (IL-6) signaling is a therapeutic option for the treatment of RA [2][3][4][5][6][7][8][9]. Sarilumab is a human IgG1 monoclonal antibody that binds specifically to both soluble and membrane-bound IL-6 receptors (sIL-6Ra and mIL6Ra), and has been shown to inhibit IL-6-mediated signaling through these receptors [2][3][4]. Sarilumab has been approved for the treatment of moderate-to-severe RA in the United States, Canada, and Europe [10][11][12].…”