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

Abstract

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.

Interstitial Lung Disease in Rheumatoid Arthritis: A Practical Review

“…Indeed, a dose-dependent beneficial effect of MTX on the risk of developing RA-ILD has been demonstrated (77) (Table 3). The Warrick global score (WGS) was significantly lower in patients treated with a MTX dosage ≥ 15 mg/week as compared with patients treated with MTX < 15 mg/week or patients naïve to MTX (77). As exposed earlier, in fact, RA-ILD and MIP are distinct entities, with MTX being causative of MIP but protective against the development of RA and RA-ILD; therefore, the detection of RA-ILD would not necessarily imply the discontinuation of MTX.…”

Choosing pharmacotherapy for ILD in patients with connective tissue disease

“…In this cohort higher rates of RA-ILD were found in those who had never taken MTX (4.8%) compared with those who had (2.5%), and MTX use was associated with a longer time to the development of ILD. Several other studies have further supported these findings [ 38 – 41 ]; therefore, MTX should no longer be routinely discontinued in the rheumatoid patient with well-controlled joint disease who develops ILD.…”

Targeting Progression in Pulmonary Fibrosis: An Overview of Underlying Mechanisms, Molecular Biomarkers, and Therapeutic Intervention

“…In the pre-antifibrotic era, immunosuppression was long considered the cornerstone of CTD-ILD treatment with two main purposes: ILD-onset prevention and the deceleration of ILD progression once existent. In RA, an historical debate about the role of methotrexate (MTX), which is considered to be highly effective for articular involvement but with potential lung toxicity, has been reappraised based on large data documenting a beneficial effect of MTX in preventing RA-ILD [144], reducing RA-ILD progression [145], and improving RA-ILD mortality [146]. Similarly, a protective role of abatacept (Aba)-a T-cell-activation inhibitor-and rituximab (RTX)-an anti-CD20 chimeric monoclonal antibody-in ILD progression has been postulated.…”