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Publications

Journal Article Ahead of print

PubMed: 42949113 DOI: 10.1093/rheumatology/keag605

Comparative effectiveness and safety of five Janus kinase inhibitors in real-world clinical practice: the multicentre ANSWER cohort.

Rheumatology (Oxford)

Authors: Yuki Etani, Yasutaka Okita, Kohei Tsujimoto, Yuichi Maeda, So Kuroda, Takaaki Noguchi, Takayuki Fujii, Akira Onishi, Tadashi Okano, Motomu Hashimoto, Iku Shirasugi, Shinya Hayashi, Yuji Nozaki, Daisuke Tomita, Akihiro Tanaka, Hideki Amuro, Hideyuki Shiba, Mahiro Yamamoto, Masaki Katayama, Wataru Yamamoto, Atsushi Kumanogoh, Seiji Okada, Ken Nakata, Kosuke Ebina

Affiliations

  • Department of Orthopaedic Surgery, The University of Osaka Graduate School of Medicine Faculty of Medicine, Suita, Japan.
  • Department of Respiratory Medicine and Clinical Immunology, The University of Osaka Graduate School of Medicine Faculty of Medicine, Suita, Japan.
  • Department of Medical Innovation, The University of Osaka Hospital, Suita, Japan.
  • Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Center for Senile Degenerative Disorders (CSDD), Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
  • Department of Clinical Immunology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
  • Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan.
  • Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
  • Department of Hematology and Rheumatology, Kindai University School of Medicine, Sakai, Japan.
  • First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
  • Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
  • Department of Rheumatology, Osaka Red Cross Hospital, Osaka, Japan.
  • Department of Health Information Management, Kurashiki Sweet Hospital, Kurashiki, Japan.
  • Department of Health and Sport Sciences, The University of Osaka Graduate School of Medicine Faculty of Medicine, Suita, Japan.
  • Department of Sports Medical Biomechanics, The University of Osaka Graduate School of Medicine Faculty of Medicine, Suita, Japan.

Abstract

OBJECTIVES

To compare treatment effectiveness and safety among five Janus kinase inhibitors (JAKi) in patients with rheumatoid arthritis (RA) and to identify factors associated with treatment discontinuation in real-world clinical practice.

METHODS

This retrospective multicentre study used data from the ANSWER cohort in Japan. RA treatment courses initiating tofacitinib, baricitinib, peficitinib, upadacitinib, or filgotinib between 2013 and 2025 were included. Treatment discontinuation due to ineffectiveness and adverse events was evaluated using Kaplan-Meier analysis and multivariable Cox proportional hazards models with multiple imputation. Analyses were adjusted for patient, disease, and treatment characteristics, including prior treatment history.

RESULTS

A total of 1,798 treatment courses from 1,240 patients were analysed. Discontinuation risk due to ineffectiveness was lower with upadacitinib (HR 0.33, 95% CI 0.24 to 0.47) and filgotinib (HR 0.59, 95% CI 0.42 to 0.85) than with tofacitinib (reference), baricitinib (HR 0.82, 95% CI 0.63 to 1.06), and peficitinib (HR 1.23, 95% CI 0.89 to 1.70). Differences in discontinuation due to adverse events were observed only between upadacitinib (HR 0.57, 95% CI 0.38 to 0.85) and peficitinib (reference). Prior IL-6i or JAKi use increased ineffectiveness-related discontinuation for tofacitinib, baricitinib, and peficitinib, but not upadacitinib (IL-6i/JAKi: HR 0.67/1.14, 95% CI 0.38-1.16/0.65-1.98) or filgotinib (HR 0.83/1.38, 95% CI 0.45-1.53/0.72-2.65).

CONCLUSIONS

Treatment effectiveness and safety differed among JAKi in real-world clinical practice. Upadacitinib and filgotinib were associated with higher treatment persistence, and the adverse impact of prior IL-6 inhibitor or JAKi exposure was not evident for these agents.

MeSH

Safety, Rheumatic Diseases, Drug-Related Side Effects And Adverse Reactions, Janus Kinases, Therapeutics, Janus Kinase Inhibitors