Among patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD), acute exacerbations (ILD-AE) were found to be associated with usual interstitial pneumonia (UIP) pattern, but not methotrexate (MTX) use, according to study results published in Rheumatology. However, both UIP pattern and nonuse of MTX predicted mortality due to ILD-AE in RA-ILD.   

Researchers retrospectively reviewed data from patients who received care for RA-ILD at a participating hospital in Japan between January 2007 and December 2019. Clinical characteristics were compared between patients who did and did not develop ILD-AE after a diagnosis of RA-ILD. Clinical features were also compared between patients who did and did not survive after admission for ILD-AE. All patients underwent imaging of the lungs using high-resolution computed tomography (HRCT). RA-ILD findings were classified as UIP or non-UIP pattern, according to existing clinical guidelines that were modified for application to RA-ILD. Researchers used multiple logistic regression to identify correlates of acute exacerbations in ILD and Cox proportional hazard models to determine risk factors for mortality in patients with ILD-AE.

Study data from 165 patients (mean age, 73.6±9.7 years; 71.9% women) were analyzed. Overall, 30 patients (22.2%) developed ILD-AE, among whom 13 (43.3%) died. All patients with ILD-AE were hospitalized. In general, patient characteristics were comparable between the groups with and without acute exacerbations. The ILD-AE and non-ILD-AE groups did not differ in terms of current or past MTX use and had similar prevalence rates of ever smoking, rheumatoid factor positivity, anticitrullinated protein antibody positivity, and comorbid cardiovascular disease.

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In multivariate analyses, the UIP vs non-UIP pattern was significantly associated with ILD-AE occurrence (odds ratio [OR], 2.55; 95% CI, 1.05-6.20; P =.038). Cox proportional hazards model showed that among patients with ILD-AE, current MTX use was associated with survival (hazard ratio [HR], 0.16; 95% CI, 0.04-0.72; P =.0016), whereas UIP pattern was significantly associated with death (HR, 4.67; 95% CI, 1.02-21.45; P =.048). Median age at ILD-AE onset was significantly more among nonsurvivors compared with survivors (80 vs 70 years; P =.003). However, in models that adjusted for UIP pattern and current MTX use, older age was not significantly predictive of death.

According to these data, a UIP pattern on HRCT may predict the development of acute exacerbation in RA-ILD. Current MTX use was not associated with acute exacerbation and appeared to increase survival rates among patients who developed AE-ILD.

Primary study limitations included the retrospective design, the single study center, and the small cohort size, which may limit data generalizability. Further study in a prospective cohort is necessary to better determine the risk factors for ILD-AE and death in patients with RA-ILD. 

“To our knowledge, this study is the first to report that MTX has no harmful effects on ILD-AE, instead of RA-ILD itself,” the researchers noted. Despite its immunosuppressive effects, MTX may be “[less] harmful in RA-ILD as was previously thought.”


Izuka S, Yamashita H, Iba A, Takahashi Y, Kaneko H. Acute exacerbation of rheumatoid arthritis–associated interstitial lung disease: clinical features and prognosis. Rheumatology (Oxford). Published online November 25, 2020. doi:10.1093/rheumatology/keaa608