Ivarmacitinib Effective in Rheumatoid Arthritis Patients having inadequate response to conventional synthetic DMARDs, finds study

A new clinical study highlighted the potential of ivarmacitinib, a selective Janus kinase (JAK) 1 inhibitor, as an effective treatment for patients with moderate-to-severe active rheumatoid arthritis (RA) who did not respond adequately to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The findings were published in the recent issue of Annals of the Rheumatic Diseases.

The double-blind, placebo-controlled study randomized a total of 566 patients into 3 groups to evaluate the efficacy and safety of ivarmacitinib over 52 weeks. The patients received either a placebo (n=188), ivarmacitinib 4 mg (n=189), or ivarmacitinib 8 mg (n=189) daily. Background csDMARDs were permitted during the trial. After 24 weeks, patients initially receiving a placebo switched to ivarmacitinib 4 mg for the remainder of the trial.

At the primary evaluation point of 24 weeks, both doses of ivarmacitinib demonstrated significantly superior efficacy when compared to the placebo. The proportion of patients achieving a 20% improvement in the American College of Rheumatology response criteria (ACR20) was 70.4% in the 4 mg group and 75.1% in the 8 mg group, markedly higher than the placebo group's 40.4%.

Further metrics showed numerically better disease control in the ivarmacitinib groups, as evidenced by higher rates of Disease Activity Score (DAS28) reductions. DAS28 assessments using C-reactive protein (CRP) levels revealed more patients achieving scores of <2.6 or ≤3.2 in the treatment groups when compared to placebo.

The patient-reported outcomes also indicated sustained improvement over 52 weeks, including among patients initially on placebo who switched to ivarmacitinib after 24 weeks. Treatment-emergent adverse events (TEAEs) were common across all groups but comparable between them. The ivarmacitinib 4 mg group reported TEAEs in 81.5% of patients, while the 8 mg group showed a slightly higher rate at 90.5%.

This contrasted with 79.3% in the placebo group. Infection-related TEAEs were modestly increased in the ivarmacitinib groups. Despite the elevated TEAE incidence in ivarmacitinib groups, the safety profile was deemed manageable and aligned with expectations for other JAK inhibitors.

Overall, the study found that ivarmacitinib offers a viable therapeutic option for RA patients with insufficient csDMARD response. It provides substantial efficacy benefits with a safety profile consistent with existing treatments in its class.

Reference:

Liu, J., Jiang, Y., Zhang, S., Liu, S., Su, J., Lin, C., He, X., Wu, R., Yang, L., Liu, H., Duan, X., Xu, S., Luo, H., Liu, J., Xie, Q., Mi, C., Chen, L., Zhang, N., Gong, H., … Zeng, X. (2024). Ivarmacitinib, a selective Janus kinase 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis and inadequate response to conventional synthetic DMARDs: results from a phase III randomised clinical trial. Annals of the Rheumatic Diseases. https://doi.org/10.1136/ard-2024-226385