Tofacitinib Reduces KL-6 Levels in Patients With Rheumatoid Arthritis-Associated Interstitial Lung Disease. Results Of A Phase II Investigator-Initiated Study
In brief
Tofacitinib lowers KL-6 by roughly 2,200 units in RA-ILD patients
In a phase II trial of 39 rheumatoid arthritis-associated interstitial lung disease patients, tofacitinib 5 mg twice daily reduced serum KL-6 from about 34,400 to 32,200 units over 48 weeks. Adverse events were common (92%) and mortality/ progressive fibrosis occurred in 38.5 per 100 patient-years, with a modest FVC drop of 72 mL. Further study is needed to determine whether the biomarker decline translates into meaningful clinical benefit.
- Journal
- Respiratory medicine (Q1)
- Published
- 10 September 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Jorge Rojas-Serrano, Espiridión Ramos-Martínez, Mayra Mejía, María Fernanda Castillo-López, Valeria Lira-Boussart, Daphne Rivero-Gallegos, et al.
- PMID
- 42722091
- DOI
- 10.1016/j.rmed.2026.109150
Why clinicians should know about it
- Picked for Rheumatology (paper of the day, 13 September 2026): Tofacitinib phase II RA‑ILD trial
Abstract
OBJECTIVES: To evaluate the safety and efficacy of tofacitinib in rheumatoid arthritis-associated interstitial lung disease (RA-ILD), along with KL-6 levels during 48 weeks of follow-up. METHODS: RA-ILD patients received tofacitinib 5 mg BID for 48 weeks. The primary outcome was the incidence of adverse events. Secondary outcomes included the rate of decline in FVC, the incidence of a combined outcome of mortality and/or progressive pulmonary fibrosis (PPF), disease activity, and serum levels of KL-6 as a biomarker of lung disease. RESULTS: Thirty-nine patients participated in the trial. Thirty-six (92%) had any adverse event; Three patients died. Upper airway respiratory infections were the most frequent adverse events. Fifteen patients (38.5/100 patient-years) had the combined outcome of mortality and/or PPF. At the final visit, 51% of patients had low disease activity (SDAI index). The rate of change in FVC at 48 weeks of follow-up was -72 mL. Serum KL-6 levels declined from baseline values to 48 weeks of follow-up (baseline LSM 34358 mU/mL to 32191 mU/mL, with an LSM decline of -2167 mU/L). Nine patients initiated nintedanib during the trial; the decline in KL-6 was no different in nintedanib-treated patients, nor was the incidence of adverse events. CONCLUSION: This trial estimates the rates of adverse events, mortality, low disease activity, PPF, decline in FVC in RA-ILD, and decline in serum KL-6 in patients treated with tofacitinib NCT05246293.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.