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Impact of concomitant methotrexate on JAK inhibitors in rheumatoid arthritis-associated interstitial lung disease: a retrospective single-centre study from the KEIO-RA cohort
K. Suzuki1, M. Akiyama2, K. Shimanuki3, Y. Kaneko4
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. mitsuaki@keio.jp
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
CER19334
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PMID: 41511752 [PubMed]
Received: 21/09/2025
Accepted : 24/11/2025
In Press: 05/01/2026
Abstract
OBJECTIVES:
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) complicates disease management due to the limited methotrexate (MTX) use. Janus kinase (JAK) inhibitors are effective as monotherapy, but the impact of concomitant MTX in RA-ILD remains unclear and controversy. We compared the clinical course of patients with RA-ILD receiving JAK inhibitors with or without MTX.
METHODS:
We analysed consecutive RA-ILD patients treated with JAK inhibitors in the KEIO-RA cohort (2013–2025), a retrospective single-centre longitudinal cohort. Patients were stratified by concomitant MTX use. The primary outcome was JAK inhibitor retention rates for 24 months and secondary outcomes included ILD progression (KL-6, %FVC, and HRCT scores), arthritis activity improvement (CDAI), glucocorticoid dose reduction, and adverse events.
RESULTS:
We evaluated 86 treatment courses; 26.7% (n=23) received JAK inhibitors with MTX. The overall 24-month retention rate was 42.3%. Retention rates did not differ between MTX and non-MTX groups (47.9% vs. 41.7%, p=0.43). Among courses on therapy ≥12 months, there was no significant difference between ILD progression between MTX and non-MTX groups, as indicated by KL-6 levels (309.0 to 324.0 U/mL, p=1.00; 525.0 to 507.0 U/mL, p=0.57, respectively), %FVC (96.9% to 96.7%, p=0.56; 80.6% to 82.0%, p=0.88, respectively), and HRCT score (4 to 3, p=0.72; 4 to 4, p=0.81, respectively), as well as arthritis improvement, glucocorticoid dose reduction, and safety. Multivariable analysis identified prior exposure to multiple bDMARDs or JAK inhibitors as an independent predictor of discontinuation.
CONCLUSIONS:
In RA-ILD, our study found no significant differences in the effectiveness of JAK inhibitors for both ILD and arthritis, retention, and safety, with or without MTX.
