Efficacy and safety of netakimab, anti-IL-17A monoclonal antibody, in patients with ankylosing spondylitis. Results of phase III international, multicenter, randomized double-blind clinical trial BCD-085-5/ASTERA

Abstract

Netakimab (NTK) is a humanized monoclonal antibody targeting interleukin-17A.Objective. The main objective of BCD-085-5/ASTERA study was to prove superiority of NTK over placebo and assess its’ safety in patients with active AS.Subjects and methods. BCD-085-5/ASTERA was a double-blind, multicenter, randomized, placebo-controlled, phase III study, which included 228 adult patients with active AS, persisting despite active treatment with NSAIDs. AS was considered active at BASDAI score ≥ 4.0. Patients were blindly randomized (1:1) to receive subcutaneous injections of NTK (120 mg) or placebo at weeks 0, 1, 2 and then every other week up to week 14. Starting from week 16 all patients from NTK group and patients from placebo group not achieving ASAS20 were switched to open label 120 mg NTK s/c once every two weeks. The total duration of treatment with NTK was 3 years.Results. Higher proportion of patients had ASAS40 response at week 16 (primary endpoint) in NTK arm compared to placebo (40,4 vs 2,6%, р <0,0001, 95% CI [27,4%; 48,1%]). Spinal pain subsided and laboratory inflammation markers decreased within one week after the first NTK injection. NTK safety profile was comparable to that of placebo. The most common for NTK adverse events were neutropenia (7,0%) and ALT increase (6,1%).Conclusion. Subcutaneous NTK at 120 mg dose demonstrated superior efficacy vs placebo, with fast onset of response and favorable safety profile when used in patients with ankylosing spondylitis.

Efficacy and safety of biological DMARDs: a systematic literature review informing the 2022 update of the ASAS-EULAR recommendations for the management of axial spondyloarthritis

“…A phase II dose-ranging study of bimekizumab, which neutralises both IL-17A and IL-17F, found response rates higher than with placebo in r-axSpA (ASAS40 29.5–45.9% vs 13.3%, low RoB) 38. Finally, netakimab was found to be efficacious in two phase II/III trials with unclear RoB, in patients with r-axSpA (ASAS40 40.4–72.7% vs 2.6–14.3%) 36 37…”

“…In total, 14 placebo-controlled trials assessed the efficacy of IL-17i (table 2, online supplemental tables S3.37−S3.66). 26–39 Patients with r-axSpA on secukinumab showed greater improvement compared to placebo in two phase III trials (ASAS20 58.1–60.5% vs 36.6–36.8%, low/unclear RoB) 26 28. Another phase III trial at low RoB saw numerically higher response rates for secukinumab compared to placebo in patients with r-axSpA, although results were not statistically significant (ASAS20 59.5–61.5% vs 47.0%) (table 3).…”

The 2023 pipeline of disease-modifying antirheumatic drugs (DMARDs) in clinical development for spondyloarthritis (including psoriatic arthritis): a systematic review of trials

“…In ASTERA, ASAS40, response rates were 40.4% with NTK vs 2.6% with placebo at week 16. 14 In PATERA, a higher proportion of patients reached American College of Rheumatology (ACR) 20 (82%) and ACR50 (70%) at week 24 with NTK vs placebo (9% and 6%, respectively). 15 Approved since 2016 in Japan for treating PsA, brodalumab is a fully human monoclonal antibody that binds to the IL-17 receptor subunit A (IL-17RA) and inhibits the activity of both IL-17A and F. For axSpA, a completed phase III trial showed positive results with ASAS40 response rates of 45.5% at week 16 and 61.6% at week 68.…”