Современная ревматология (Aug 2021)

Effectiveness and safety of levilimab in combination with methotrexate in treatment of patients with active rheumatoid arthritis resistant to methotrexate monotherapy (double-blinded randomized placebo controlled phase III clinical study SOLAR)

  • V. I. Mazurov,
  • M. A. Korolev,
  • A. M. Prystrom,
  • E. V. Kunder,
  • N. F. Soroka,
  • A. A. Kastanayan,
  • T. V. Povarova,
  • T. V. Plaksina,
  • O. V. Antipova,
  • D. G. Kretchikova,
  • S. A. Smakotina,
  • O. A. Tciupa,
  • E. V. Puntus,
  • T. A. Raskina,
  • L. N. Shilova,
  • T. V. Kropotina,
  • O. B. Nesmeyanova,
  • T. A. Popova,
  • I. B. Vinogradova,
  • Yu. N. Linkova,
  • E. A. Dokukina,
  • A. V. Plotnikova,
  • P. S. Pukhtinskaia,
  • A. V. Zinkina-Orikhan,
  • A. V. Eremeeva,
  • A. A. Lutckii

DOI
https://doi.org/10.14412/1996-7012-2021-4-13-23
Journal volume & issue
Vol. 15, no. 4
pp. 13 – 23

Abstract

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Levilimab is anti-interleukin-6 receptor (IL6R) monoclonal antibody. The article presents data obtained during 24 weeks of the SOLAR phase III study.Objective: to confirm efficacy and safety of levilimab in combination with methotrexate (MTX) in patients with methotrexate resistant active rheumatoid arthritis (RA).Patients and methods. 154 adult patients, aged ≥18 years with the diagnosis of RA (ACR/EULAR 2010) and confirmed disease activity at screening despite treatment with MTX for at least 12 weeks (in a stable dose 15-25 mg/week). Patients were randomized 2:1 in levilimab (162 mg once a week, subcutaneously) + MTX (n=102) or placebo + MTX (n=52) group.The hypothesis of superiority of levilimab over placebo was tested for two co-primary efficacy endpoints: proportion of subjects who achieved ACR20 at week 12 and proportion of subjects who achieved low disease activity (LDA) of RA (DAS28-CRP <3.2) at week 24. Safety was assessed through monitoring of adverse events (AEs).Results and discussion. Seventy (68.6%) subjects who received levilimab and 20 (38.5%) who received placebo achieved ACR20 response at week 12. Fifty three (52%) subjects who received levilimab and 3 (5,8%) subjects who received placebo achieved LDA at week 24. The most common adverse events (reported in ≥5% of subjects) in levilimab and placebo arms, respectively were (by decreasing frequency): blood c holesterol increase (24% vs 12%), alanine aminotransferase elevation (11% vs 8%), lymphocyte count decrease (9% vs 8%), blood total bilirubin increase (11% vs 0%), blood triglycerides increase (10% vs 2%), aspartate aminotransferase elevation (7% vs 4%), positive interferon-gamma release assay (IGRA) with M.tuberculosis antigen blood test (5% vs 6%), absolute neutrophil count decrease (8% vs 0%). No deaths were occurred.Conclusion. The study confirmed superior efficacy of levilimab + MTX over placebo + MTX in subjects with MTX resistant active RA. Levilimab showed favorable safety profile and low immunogenicity. No new important safety risks were detected.

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