Protective effect of methotrexate on lung function and mortality in rheumatoid arthritis–related interstitial lung disease: a retrospective cohort study

Abstract

Background: Studies on the risk and protective factors for lung function decline and mortality in rheumatoid arthritis–related interstitial lung disease (RA-ILD) are limited. Objectives: We aimed to investigate clinical factors and medication uses associated with lung function decline and mortality in RA-ILD. Methods: This retrospective cohort study examined the medical records of patients with RA-ILD who visited Severance Hospital between January 2006 and December 2019. We selected 170 patients with RA-ILD who had undergone at least one spirometry test and chest computed tomography scan. An absolute decline of ⩾10% in the functional vital capacity (FVC) was defined as significant decline in pulmonary function. Data for analysis were retrieved from electronic medical records. Results: Ninety patients (52.9%) were female; the mean age was 64.0 ± 10.2 years. Multivariate logistic regression showed that a high erythrocyte sediment rate level at baseline [odds ratio (OR) = 3.056; 95% confidence interval (CI) = 1.183–7.890] and methotrexate (MTX) use (OR = 0.269; 95% CI = 0.094–0.769) were risk and protective factors for lung function decline, respectively. Multivariate Cox regression analysis indicated that age ⩾65 years (OR = 2.723; 95% CI = 1.142–6.491), radiologic pattern of usual interstitial pneumonia (UIP) or probable UIP (OR = 3.948; 95% CI = 1.522–10.242), baseline functional vital capacity (FVC) % predicted (OR = 0.971; 95% CI = 0.948–0.994), and MTX use (OR = 0.284; 95% CI = 0.091–0.880) were predictive of mortality. Conclusion: We identified risk and protective factors for lung function decline and mortality in patients with RA-ILD. MTX use was associated with favorable outcome in terms of both lung function and mortality in our cohort.

Incidence, risk factors, and prognosis of acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis

“…A large prospective study suggested that MTX pneumonitis was rare [ 57 ]. Recent studies demonstrated that MTX improved lung function and prognosis in RA-ILD [ 58 , 59 ]. However, the relationship between MTX use and AE-RA-ILD remains controversial.…”

Potential Rheumatoid Arthritis-Associated Interstitial Lung Disease Treatment and Computational Approach for Future Drug Development

“…Juge et al [ 41 ] further advocated for the positive effect of MTX using a case–control study that revealed a lower risk of RA-ILD in MTX ever-users compared with MTX never-users, with an average delay of 3.6 years in ILD detection. MTX was also suggested to be a protective factor against lung function decline and mortality in cohorts of patients with RA-ILD when provided after RA-ILD incidence [ 42 ]. A phase 4 randomized controlled trial (PULMORA) is in progress to compare the effects of MTX with those of the Janus kinase (JAK) inhibitor tofacitinib [ 43 ].…”

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.…”