Methotrexate Protective Against Mortality and Lung Function Decline in RA-ILD

Methotrexate use is protective against mortality and lung function decline in patients with rheumatoid arthritis-related interstitial lung disease (RA-ILD), according to study findings published in Therapeutic Advances in Respiratory Disease.

Researchers conducted a retrospective cohort study to analyze the effects of methotrexate on lung function decline and mortality in patients with RA-ILD between January 2006 and December 2019 at Severance Hospital in Seoul, South Korea.

The researchers collected relevant patient data from electronic medical records, including demographics, dates of RA and RA-ILD diagnoses, smoking history, pulmonary function test results, list of medications, survival status, last follow-up date, and death date (including lung transplantation dates that were considered as death dates due to the removal of the fibrosed lungs).

Additional testing included spirometry, high-resolution computed tomography (HRCT) scans, erythrocyte sedimentation rate (ESR), anticyclic citrullinated peptide (anti-CCP) antibody testing, C-reactive protein levels, and immunoglobulin M (IgM)-rheumatoid factor (RF) measurements.

Of the total cohort (n=170; 52.9% women; mean age, 64.0±10.2 years), 45.9% were smokers or had previously smoked and 39.4% demonstrated radiologic patterns of usual interstitial pneumonia (UIP). The majority of patients (92.1%) tested positive for anti-CCP antibodies at baseline. A total of 21.6% of patients who underwent spirometry testing demonstrated significant pulmonary deficits, as observed by an absolute forced vital capacity (FVC) decline of at least 10%. The majority of patients (85.9%) received treatment with oral glucocorticoids; 46.5% received methotrexate.

During the follow-up period, 17.1% of the total participants died, with a mean overall survival of 11.5 years. Mean overall survival was further reduced to 9.6 years among the patients who had radiographic signs of UIP, which significantly differed from those without UIP (P <.001).

Risk factors predicting mortality after adjustments for sex and smoking history included age 65 years and older (odds ratio [OR], 2.723; 95% CI, 1.142-6.491; P =.024), radiologic patterns suggestive of UIP (OR, 3.948; 95% CI, 1.522-10.242; P =.005), methotrexate use (OR, 0.284; 95% CI, 0.091-0.880; P =.029), and baseline FVC% predicted (OR, 0.971; 95% CI, 0.948-0.994; P =.012). Methotrexate use was the only positive predictor of survival.

In addition to mortality, methotrexate use was also protective against lung function decline (OR, 0.269; 95% CI, 0.094-0.769; P =.014).

Study limitations included selection bias, missing data that may have affected the use of the most recent definitions of progressive fibrosing phenotype of ILD, and the retrospective study design.

“We identified risk and protective factors for lung function decline and mortality in patients with RA-ILD,” the study authors said. “[Methotrexate] use was associated with favorable outcome in terms of both lung function and mortality, while older age, lower baseline FVC, and radiologic patterns of UIP or probable UIP were associated with unfavorable outcome.”