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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1501146

Impact of Janus kinase inhibitors and methotrexate on interstitial lung disease in rheumatoid arthritis patients

Provisionally accepted
Shota Kurushima Shota Kurushima 1Tomohiro Koga Tomohiro Koga 1*Masataka Umeda Masataka Umeda 1Naoki Iwamoto Naoki Iwamoto 1Ritsuko Miyashita Ritsuko Miyashita 2Takatomo Tokito Takatomo Tokito 2Daisuke Okuno Daisuke Okuno 2Hirokazu Yura Hirokazu Yura 2Hiroshi Ishimoto Hiroshi Ishimoto 2Takashi Kido Takashi Kido 2Noriho Sakamoto Noriho Sakamoto 2Yukitaka Ueki Yukitaka Ueki 3Hiroshi Mukae Hiroshi Mukae 2Atsushi Kawakami Atsushi Kawakami 1
  • 1 Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • 2 Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • 3 Rheumatic Disease Center, Sasebo Chuo Hospital, Sasebo, Japan

The final, formatted version of the article will be published soon.

    A retrospective study was performed to compare the progression of rheumatoid arthritisassociated interstitial lung disease (RA-ILD). Although RA treatment has been revolutionized by the introduction of new drugs such as biological disease-modifying anti-rhematic drugs (bDMARDs) and Janus kinase inhibitors (JAKi), little is known about how these treatments affect the progression of ILD. This retrospective study included 93 RA-ILD patients who initiated treatment with JAKi, abatacept, or tumor necrosis factor inhibitors (TNFi) between 2017 and 2020. Worsening ILD was quantified by changes in chest computed tomography (CT) scans between baseline and follow-up (mean 14 months, range 6-51 months). Response to treatment was evaluated using Disease Activity 2 Score-28 with erythrocyte sedimentation rate (DAS28-ESR). As a result, worsening ILD was detected in 19.4% (7/36), 16.7% (5/30), and 22.2% (6/27) of patients treated with JAKi, abatacept, and TNFi, respectively. Multivariate analysis identified >10% fibrotic lesions (P=0.015) and female gender (P=0.043) as significant predictors of worsening ILD. DAS28-ESR-based non-responder status was also significantly associated with worsening ILD (P=0.0085). Although not statistically significant, co-treatment with MTX tended to reduce the risk of worsening ILD. To evaluate the potential beneficial effects of combination therapy on epithelial-mesenchymal transition (EMT), we also performed in vitro experiments. We found that combination treatment with baricitinib and methotrexate significantly inhibited IL-6-induced EMT in A549 lung cells more than baricitinib alone by comparing the expression of the EMT marker N-cadherin. Co-treatment with JAKi and methotrexate may prove beneficial in modifying key events underlying the pathogenesis of RA-ILD.

    Keywords: Rheumatoid arthritis, Interstitial Lung Disease, RA-ILD, JAK inhibitors, Methotrexate, Epithelial-Mesenchymal Transition

    Received: 24 Sep 2024; Accepted: 02 Dec 2024.

    Copyright: © 2024 Kurushima, Koga, Umeda, Iwamoto, Miyashita, Tokito, Okuno, Yura, Ishimoto, Kido, Sakamoto, Ueki, Mukae and Kawakami. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Tomohiro Koga, Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

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