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Methotrexate, leflunomide, and tacrolimus use and the progression of rheumatoid arthritis-associated interstitial lung disease.

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OBJECTIVE To examine the association between methotrexate, leflunomide, and tacrolimus use and the progression of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). METHODS The Korean RA-ILD cohort prospectively enrolled patients… Click to show full abstract

OBJECTIVE To examine the association between methotrexate, leflunomide, and tacrolimus use and the progression of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). METHODS The Korean RA-ILD cohort prospectively enrolled patients with RA-associated ILD at multiple centres from 2015 to 2018 and followed up with them for 3 years. ILD progression was defined by any of the followings: a decrease of ≥ 10% in forced vital capacity, a decrease of ≥ 15% in the diffusing capacity of the lung for carbon monoxide, or death from respiratory failure. RESULTS Of 143 patients, 64 patients experienced ILD progression during a median follow-up period of 33 months. The use of methotrexate (adjusted hazard ratio [aHR], 1.06; 95% CI, 0.59-1.89), leflunomide (aHR, 1.75; 95% CI, 0.88-3.46), and tacrolimus (aHR, 0.94; 95% CI, 0.52-1.72) did not increase the risk of ILD progression. However, the association between leflunomide use and the risk of ILD progression was significant in subgroups with poor lung function (aHR, 8.42; 95% CI, 2.61-27.15). Older age, male sex, a shorter RA duration, higher RA disease activity, and extensive disease at baseline were independently associated with ILD progression. CONCLUSION None of the three treatments increased the risk of RA-associated ILD progression, except for leflunomide, which increased the risk of ILD progression in patients with severe ILD. The appropriate use of conventional synthetic disease-modifying antirheumatic drugs considering RA disease activity and ILD severity would be important for the management of RA-associated ILD.

Keywords: leflunomide; disease; progression; lung; ild progression; use

Journal Title: Rheumatology
Year Published: 2022

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