Sarilumab is a biologic disease-modifying antirheumatic drug (bDMARD) that targets cytokines for the treatment of patients with rheumatoid arthritis. This monoclonal antibody targets cytokines IL-6R and inhibits IL-6 mediated signaling. The presence of IL-6R in the synovial fluid of patients with rheumatoid arthritis has been linked with systemic inflammation, fatigue, and joint destruction. Rheumatoid arthritis is commonly treated with synthetic DMARDS such as methotrexate as first-line therapy, but many patients have built up an intolerance or have not mounted an adequate response to the therapy. Adalimumab, another biologic disease-modifying antirheumatic drug, like sarilumab, is globally approved for the treatment of rheumatoid arthritis and has proven successful in patients who do not respond well to methotrexate. Adalimumab targets TNF-a, a different target than sarilumab for the treatment of rheumatoid arthritis. The MONARCH trial was conducted to compare the efficacy and safety of sarilumab and adalimumab monotherapy in patients who did not reach clinical remission on synthetic DMARD therapy.
The MONARCH trial was a multicenter, randomized, active-controlled, double-blind, double-dummy, phase 3 superiority trial conducted in multiple countries that ran for 24 weeks. Inclusion criteria for patients included patients greater than 18 years of age, who fulfilled American College of Rheumatology (ACR)/European League Against Rheumatism Classification Criteria for RA and ACR class I–III functional status; had active RA, and either intolerant or considered inappropriate for continued treatment with methotrexate. The primary efficacy endpoint was a change from baseline in disease-joint activity using erythrocyte sedimentation rate (ESR). Other secondary efficacy endpoints included DAS28-ESR remission, Health Assessment Questionnaire-Disability Index (HAQ-DI); ACR 20% (ACR20), 50% (ACR50) and 70% (ACR70) responses; Medical Outcomes Short Form 36 Health Survey (V.2) (SF-36) physical component summary (PCS) score and mental component summary (MCS) score and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Clinical Disease Activity Index (CDAI). Safety was measured by assessing treatment-emergent adverse events, serious adverse events reported by investigators, as well as lab tests.
Within this study, the primary endpoint was reached. Sarilumab at a dose of 200 mg every 2 weeks was superior to adalimumab 40 mg every 2 weeks with a mean change from baseline to week 24 in DAS28-ESR of -1.08 with a 95% confidence interval. In comparison to adalimumab, the odds of reaching remission were three times more likely with sarilumab at week 12 and five times more likely at week 24. In terms of safety, the adverse events reported in both groups were similar, as well as the rate of discontinuation between the groups.
Biologics for the treatment of rheumatoid arthritis offers new options for patients who are not getting the help they need from older therapies such as methotrexate. This trial showed that sarilumab was superior to adalimumab in the reduction of disease activity with no large difference in safety. One of the most important things in patients suffering from rheumatoid arthritis is their ability to perform functional tasks without pain and fatigue. Compared to adalimumab, patients who received sarilumab reported a greater improvement in daily activities with less pain. Biologic therapy targeting different cytokines that play a role in the pathogenesis of rheumatoid arthritis is changing the way of life for patients who are plagued by this disease.
1. Burmester GR, Lin Y, Patel R, et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2017;76(5):840-847. doi:10.1136/annrheumdis-2016-210310
2. Emery P, Rondon J, Parrino J, et al. Safety and tolerability of subcutaneous sarilumab and intravenous tocilizumab in patients with rheumatoid arthritis. Rheumatology (Oxford). 2019;58(5):849-858. doi:10.1093/rheumatology/key361