A dose-dependent beneficial effect of methotrexate on the risk of interstitial lung disease in rheumatoid arthritis patients

OBJECTIVES: The aim of the study was to assess the influence of different factors, including treatment, on the risk of ILD in the course of RA. METHODS: A total of 109 RA patients were included in the analysis. High-resolution computed tomography (HRCT) of chest was obtained in each patient. Patients were classified as having ILD (ILD group) or not (N-ILD group). The ILD was graded using the semi-quantitative Warrick scale of fibrosis. Warrick extent score (WES) and Warrick severity score (WSS) were calculated separately for each patient, then combined to obtain a global score (WGS). RESULTS: In univariate analysis the presence of ILD was associated positively with age (P = 5x10(-6)) and negatively with MTX treatment (P = 0.0013), mean MTX dose per year of treatment (P = 0.003) and number of DMARDs used (P = 0.046). On multivariate analysis only age and treatment with MTX were independently associated with the presence of ILD. WGS was significantly lower in patients treated with MTX in a dose of ≥15 mg/week (MTX≥15 group) as compared to patients treated with lower doses of MTX (0<MTX<15 group) or not treated with MTX (N-MTX group) (P = 0.04 and P = 0.037, respectively). The ILD prevalence was higher in N-MTX group than in 0<MTX<15 group (P = 0.0036) and MTX≥15 group (0.0007). The difference in ILD prevalence between MTX≥15 and 0<MTX<15 groups was not significant, but the latter group had higher WES (P = 0.044) and trended to have higher WSS and WGS. CONSCLUSIONS: We found a beneficial effect of MTX on RA-ILD. Importantly, this effect seems to be dose dependent.