MTX use in the treatment of RA-associated-interstitial lung disease: a systematic review

OBJECTIVES: To assess the progression of the interstitial lung disease related to RA (RA-ILD) with 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 (1 study) and survival (5 studies). MTX was not associated with a risk of developing ILD (nine 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.