Comparative effectiveness of biological disease-modifying antirheumatic drugs and Janus kinase inhibitor monotherapy in rheumatoid arthritis

Akira Onishi; Hirotaka Yamada; Wataru Yamamoto; Ryu Watanabe; Ryota Hara; Masaki Katayama; Yasutaka Okita; Yuichi Maeda; Hideki Amuro; Yonsu Son; Ayaka Yoshikawa; Kenichiro Hata; Motomu Hashimoto; Jun Saegusa; Akio Morinobu

doi:10.1093/rheumatology/kead620

Comparative effectiveness of biological disease-modifying antirheumatic drugs and Janus kinase inhibitor monotherapy in rheumatoid arthritis

Rheumatology (Oxford). 2023 Nov 21:kead620. doi: 10.1093/rheumatology/kead620. Online ahead of print.

Authors

Akira Onishi¹, Hirotaka Yamada², Wataru Yamamoto³, Ryu Watanabe⁴, Ryota Hara⁵, Masaki Katayama⁶, Yasutaka Okita⁷, Yuichi Maeda⁷, Hideki Amuro⁸, Yonsu Son⁸, Ayaka Yoshikawa⁹, Kenichiro Hata⁹, Motomu Hashimoto⁴, Jun Saegusa², Akio Morinobu¹⁰

Affiliations

¹ Department of Advanced Medicine for Rheumatic Diseases, Kyoto University Graduate School of Medicine, Kyoto, Japan.
² Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan.
³ Department of Health Information Management, Kurashiki Sweet Hospital, Okayama, Japan.
⁴ Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
⁵ Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan.
⁶ Department of Rheumatology and Clinical Immunology, Osaka Red Cross Hospital, Osaka, Japan.
⁷ Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
⁸ First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
⁹ Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University, Osaka, Japan.
¹⁰ Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

PMID: 37988163
DOI: 10.1093/rheumatology/kead620

Abstract

Objectives: To examine the effectiveness and drug tolerability of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitor (JAKi) monotherapy in patients with rheumatoid arthritis (RA) in a multicentre cohort study.

Methods: Patients with RA initiated with bDMARD/JAKi monotherapy without conventional synthetic DMARDs were included. Monotherapy regimens were categorised as interleukin-6 receptor inhibitors (IL-6Ri), cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4Ig), JAKi, or tumour necrosis factor inhibitors (TNFi). Multiple propensity score-based inverse probability weighting (IPW) was used to reduce selection bias. Linear mixed-effect models with IPW were used to examine changes in the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) at 24 weeks, and drug retention was compared among monotherapy using IPW Cox proportional hazards models.

Results: A total of 849 treatment courses from 635 patients were included (IL-6Ri, 218; CTLA4Ig, 183; JAKi, 92; TNFi, 356). The difference in change in DAS28-ESR at week 24 as the primary outcome was -0.93 (95% CI: -1.20 to -0.66) lower in the IL-6Ri group than TNFi, while that of CTLA4Ig and JAKi was similar with that of TNFi (-0.20 [-0.48 to 0.08], -0.25 [-0.67 to 0.16], respectively). IL-6Ri use was associated with significantly lower overall drug discontinuation than TNFi use (hazard ratio = 0.55 [0.39-0.78], P = 0.001). Similar retention rates were identified among CTLA4Ig and JAKi compared to TNFi.

Conclusion: In the analysis with IPW to reduce selection bias, IL-6Ri monotherapy was superior to TNFi monotherapy in terms of effectiveness and drug retention. No significant differences were identified between CTLA4Ig, JAKi, and TNFi monotherapy.

Keywords: Janus kinase inhibitor; abatacept; antirheumatic agents; interleukin-6 inhibitors; rheumatoid arthritis; tumor necrosis factor inhibitors.