Background: varmacitinib, a selective Janus kinase 1 inhibitor, has shown significant efficacy in patients with moderate-to-severe rheumatoid arthritis (RA) in a randomized, double-blinded, placebo-controlled phase III clinical trial (NCT04333771).

Objectives: This study aimed to explore the efficacy of Ivarmacitinib in RA patients who have not used biological disease-modifying antirheumatic drugs (bDMARDs) previously (bDMARDs-naïve RA patients).

Methods: This post-hoc study utilized the data from the phase III trial of Ivarmacitinib in patients with RA, in which moderate-to-severe RA patients with inadequate response to conventional DMARDs received 4 mg or 8 mg Ivarmacitinib or placebo daily for 24 weeks [1]. bDMARDs-naïve (n=421) patients were included for analysis.

Results: At week 24, both Ivarmacitinib 4 mg and 8 mg groups achieved significantly higher rates of achieving 20%, 50%, and 70% improvement in American College of Rheumatology response criteria (ACR20/50/70) compared to the placebo group (all P <0.001). Both Ivarmacitinib groups also had significantly higher response rates for disease Activity Score 28-C reactive protein (DAS28-CRP)≤3.2/<2.6, clinical disease activity index (CDAI)≤10/≤2.8, and simplified disease activity index (SDAI)≤11/≤3.3 (all P <0.001). Furthermore, in the Ivarmacitinib groups, the achievement rates of Health Assessment Questionnaire Disability Index (HAQ-DI)<0.5, HAQ-DI improvement≥0.22, and HAQ-DI improvement≥0.3 were all greater than in the placebo group (all P <0.01) (Figure 1).

Figure 1.

Comparison of ACR20/50/70 response rates at week 24 among groups (A). Comparison of DAS28-CRP≤3.2, CDAI≤10, and SDAI≤11 response rates at week 24 among groups (B). Comparison of DAS28-CRP<2.6, CDAI≤2.8, and SDAI≤3.3 response rates at week 24 among groups (C). Comparison of HAQ-DI improvement of ≥0.22, HAQ-DI improvement of ≥0.3, and HAQ-DI<0.5 rates at week 24 among groups (D)

**, P <0.01 in Ivarmacitinib 4 mg group compared with placebo group; ***, P <0.001 in Ivarmacitinib 4 mg group compared with placebo group; ##, P <0.01 in Ivarmacitinib 8 mg group compared with placebo group; ###, P <0.001 in Ivarmacitinib 8 mg group compared with placebo group.

Conclusion: Ivarmacitinib effectively reduces disease activity and improves health-related quality of life in bDMARDs-naïve RA patients.

REFERENCES: [1] Liu J, Jiang Y, Zhang S, et al. 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. Ann Rheum Dis. Published online November 27, 2024. doi:10.1136/ard-2024-226385.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.