No new safety signals were identified with long-term use of sarilumab for the treatment of rheumatoid arthritis (RA), according to study results published in Rheumatology.
Researchers reported safety and efficacy data from 2 open-label extension studies (EXTEND and MONARCH [ClinicalTrials.gov Identifiers: NCT01146652 and NCT02332590, respectively]). Patients in the studies were adults with RA who were treatment-naive or were ineligible, inadequate responders, or had intolerance to tumor necrosis factor inhibitors (TNFi), methotrexate, or nonbiologic disease-modifying antirheumatic drugs (DMARDs). Patients received 200 mg subcutaneous sarilumab every 2 weeks for 516 or 276 weeks in EXTEND or MONARCH trials, respectively.
In the EXTEND trial, 111 patients received sarilumab as monotherapy and 1912 received sarilumab with conventional synthetic DMARDs (csDMARDs); in the MONARCH trial, 165 received sarilumab continuously and 155 were switched to sarilumab from placebo.
Treatment-emergent adverse events (TEAEs) occurred among 88.3% of those who received sarilumab monotherapy, 92.1% of those who received sarilumab plus csDMARDs, 86.7% of those who received continuous treatment with sarilumab, and 87.1% of those who were switched to sarilumab. Serious adverse events occurred among 24.3%, 32.3%, 15.2%, and 20.0% of participants, respectively.
More than 10% of patients in all groups reported neutropenia, nasopharyngitis, and bronchitis. More than 1% of patients in all groups had severe TEAEs, including osteoarthritis, pneumonia, cholelithiasis, RA, atrial fibrillation, pulmonary embolism, Clostridium difficile infection, cellulitis, and hemorrhagic stroke.
In both the EXTEND and MONARCH trials, TEAEs led to discontinuation in up to 2.1% and 2.6% of participants, respectively, due to alanine amino transferase increase, herpes zoster, injection site erythema, and neutropenia.
The TEAEs leading to death occurred among 42 patients in the EXTEND trial and 8 in the MONARCH trial.
Overall, improvements in RA observed during the original trials were maintained during the extension period across all treatment groups and patient-reported outcomes were maintained or continued to improve among a percentage of patients who received sarilumab plus csDMARDs.
Study findings may have been biased, as data were derived from those who completed the original trials.
The study authors concluded, “Long-term treatment with sarilumab with or without background csDMARDs in patients with RA identified no new safety signals. The results are consistent with interleukin (IL)-6 signaling blockade and confirm the safety profile of sarilumab from the phase  randomized controlled trials. Improvements in clinical efficacy and patient reported outcomes including health-related quality of life, fatigue, participation and work productivity reported during the initial phase [2/3] randomized trials were maintained or further increased.”
Disclosure: This research was supported by Sanofi. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Burmester GR, Strand V, Kivitz AJ, et al. Long-term safety and efficacy of sarilumab with or without background csDMARDs in rheumatoid arthritis. Rheumatology. Published online February 2, 2023. doi:10.1093/rheumatology/kead062