levilimab + methotrexate

Levilimab + methotrexate is a combination therapy used primarily for treating active rheumatoid arthritis that is resistant to methotrexate monotherapy. Levilimab is an anti-interleukin-6 receptor (IL-6R) monoclonal antibody that works by inhibiting IL-6, which helps reduce inflammation associated with rheumatoid arthritis. When combined with methotrexate, this therapy has shown superior efficacy compared to placebo + methotrexate in clinical trials. ### Efficacy and Clinical Evidence The SOLAR study, a phase III double-blind, placebo-controlled randomized clinical trial, demonstrated the effectiveness of this combination therapy. The study was conducted at 21 clinical sites in Russia and Belarus with 154 adult subjects who had methotrexate-resistant active rheumatoid arthritis. In this trial, subjects were randomly assigned (2:1) to receive either levilimab (162 mg, subcutaneously, once weekly) + methotrexate or placebo + methotrexate. After 24 weeks, all subjects continued to receive open-label levilimab. The results confirmed the superior efficacy of levilimab + methotrexate over placebo + methotrexate in subjects with methotrexate-resistant active rheumatoid arthritis. Subjects who achieved DAS28-CRP ≤ 2.6 (disease remission) at week 24 were switched to a maintenance regimen of levilimab (every two weeks) at week 28, while those with higher disease activity continued with the weekly regimen. ### Safety Profile The safety profile of levilimab + methotrexate has been evaluated through monitoring of adverse events. The most common adverse events (reported in ≥5% of subjects) included: - Blood cholesterol increase (24-30.3%) - Alanine aminotransferase elevation (11-23%) - Lymphocyte count decrease (9-17.1%) - Blood total bilirubin increase (11-11.2%) - Blood triglycerides increase (10-13.8%) - Aspartate aminotransferase elevation (7-9.9%) - Absolute neutrophil count decrease (8-16.4%) - Positive interferon-gamma release assay with M.tuberculosis antigen blood test (5-7.2%) - Injection site reactions (5.9%) No deaths occurred during the studies, and the combination therapy showed a favorable safety profile with low immunogenicity. No new important safety risks were detected during the clinical trials. ### Ongoing Research Further research on levilimab is ongoing, including a two-stage study (NCT05800327) investigating different dosing regimens. This study aims to confirm the efficacy and safety of levilimab 648 mg IV every 4 weeks and levilimab 324 mg SC every 2 weeks, both in combination with methotrexate, for patients with active rheumatoid arthritis resistant to methotrexate monotherapy. The combination of levilimab + methotrexate represents an important treatment option for patients with rheumatoid arthritis who have not responded adequately to methotrexate alone, offering sustained efficacy and a manageable safety profile.

Other names

BCD-089 + methotrexate