Methotrexate use in the treatment of rheumatoid arthritis associated-interstitial lung disease: a systematic review

Abstract Objectives To assess the progression of the interstitial lung disease related to rheumatoid arthritis (RA-ILD) with Methotrexate (MTX) exposure, and to evaluate the lung involvement in RA non-ILD patients with MTX exposure. Methods A systematic review was performed including studies of RA patients reporting the effect of MTX on ILD, as a primary or secondary end point. Results Sixteen studies were included in the systematic review. The total number of patients was 36 444, of which 18 548 (50.8%) were declared on MTX. Patients on MTX were classified into two groups, based on whether they were experiencing ILD. Comparison with control groups was performed to assess the development and/or the progression of ILD in MTX users. Non exposed MTX subjects (N-MTX) were considered as the control group in 14 studies. To evaluate the pulmonary state, studies carried out different evaluation methods: High-Resolution Computed Tomography (10 studies), pulmonary function tests (8 studies), arterial blood gas analysis (one study) and survival (5 studies). MTX was not associated with a risk of developing ILD (9 studies). Five studies suggested that MTX was not associated with the progression of RA-ILD. An accelerated decline in lung function was observed with low-dose MTX (one study). Better survival was shown in MTX patients compared with the N-MTX group (one study). In one study, MTX use was significantly associated with the development of acute exacerbations. Conclusion MTX appears to have no association with an increased risk of ILD and/or its progression in RA patients.