Objective. Methotrexate has shown efficacy for the treatment of several diseases, especially rheumatoid arthritis (RA). Methotrexate has also been implicated as a causative agent in interstitial lung disease. Patients with RA may develop pulmonary manifestations of their disease and are at increased risk of respiratory infection. The aim of this study was to evaluate the relative risk (RR) of pulmonary disease among patients with RA treated with methotrexate.Methods. We searched the PubMed and Cochrane databases (publication dates January 1, 1990 to February 1, 2013) for double-blind, randomized, controlled trials of methotrexate versus placebo or active comparator agents in adults with RA. Studies with <100 subjects or with a duration of <24 weeks were excluded. Two investigators independently searched both databases, and all of the investigators reviewed the selected studies. We compared differences in the RR using the Mantel-Haenszel random-effects method.Results. A total of 22 studies with 8,584 participants met the inclusion criteria. Heterogeneity across studies was not significant (I 2 ‫؍‬ 3%), allowing combination of the trial results. Methotrexate was associated with an increased risk of all adverse respiratory events (RR 1.10, 95% confidence interval [95% CI] 1.02؊1.19) and respiratory infection (RR 1.11, 95% CI 1.02؊1.21). Patients treated with methotrexate were not at increased risk of death due to lung disease (RR 1.53, 95% CI 0.46؊5.01) or noninfectious respiratory events (RR 1.02, 95% CI 0.65؊1.60). A subgroup analysis of studies in which pneumonitis was described revealed an increased risk associated with methotrexate (RR 7.81, 95% CI 1.76؊34.72).Conclusion. Our study demonstrated a small but significant increase in the risk of lung disease in patients with RA treated with methotrexate compared with other disease-modifying antirheumatic drugs and biologic agents.

This study demonstrates that JAK/STAT signaling mediates the complex interplay between inflammation and cellular metabolism in RA pathogenesis.

ObjeCtive To evaluate the relative risk of pulmonary disease among patients with psoriasis, psoriatic arthritis, and inflammatory bowel disease treated with methotrexate.

Objective The relative risk of SARS–CoV‐2 infection and COVID‐19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS–CoV‐2 infection in those with RMDs and describe clinical outcomes of COVID‐19 in these patients. Methods We conducted a systematic literature review using 14 databases from January 1, 2019 to February 13, 2021. We included observational studies and experimental trials in RMD patients that described comparative rates of SARS–CoV‐2 infection, hospitalization, oxygen supplementation/intensive care unit (ICU) admission/mechanical ventilation, or death attributed to COVID‐19. Methodologic quality was evaluated using the Joanna Briggs Institute critical appraisal tools or the Newcastle‐Ottawa scale. Risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated, as applicable for each outcome, using the Mantel‐Haenszel formula with random effects models. Results Of the 5,799 abstracts screened, 100 studies met the criteria for inclusion in the systematic review, and 54 of 100 had a low risk of bias. Among the studies included in the meta‐analyses, we identified an increased prevalence of SARS–CoV‐2 infection in patients with an RMD (RR 1.53 [95% CI 1.16–2.01]) compared to the general population. The odds of hospitalization, ICU admission, and mechanical ventilation were similar in patients with and those without an RMD, whereas the mortality rate was increased in patients with RMDs (OR 1.74 [95% CI 1.08–2.80]). In a smaller number of studies, the adjusted risk of outcomes related to COVID‐19 was assessed, and the results varied; some studies demonstrated an increased risk while other studies showed no difference in risk in patients with an RMD compared to those without an RMD. Conclusion Patients with RMDs have higher rates of SARS–CoV‐2 infection and an increased mortality rate.