Study Highlights Key RA-ILD Risk Factors, Urges Early Screening

Patients with the following risk factors are likely to develop rheumatic arthritis–associated interstitial lung disease (RA-ILD): male gender, older age, ever-smoking status, pulmonary complications, the presence of rheumatoid nodules, older RA onset age, and leflunomide (LEF) usage.¹

Authors of the BMJ Open Respiratory Research study explained that ILD is among the pulmonary complications of RA, with RA-ILD being the most common. Depending on the diagnostic criteria and investigation methods, the reported incidence of ILD in patients with RA ranges from 1.3 to 5.0 per 1000 person-years. Also, RA-ILD results in a 2- to 10-fold increase in mortality, with the median survival post diagnosis being less than 3 years.²

Most patients with RA-ILD are asymptomatic or present with nonspecific symptoms, like cough or dyspnea, in the early stages.¹ Patients may remain undiagnosed if only those with pulmonary symptoms are screened using high-resolution CT. Therefore, the researchers emphasized the importance of identifying risk factors for incident RA-ILD and conducted a systematic literature review and meta-analysis to address this.

This recent study highlights key risk factors for rheumatoid arthritis–associated interstitial lung disease, emphasizing the importance of early screening to improve diagnosis and patient outcomes. | Image Credit: PH alex aviles - stock.adobe.com

They conducted their literature review using various online databases, including PubMed, Web of Science, and Scopus. Eligible studies included cohort or nested case-control studies published by March 2021 that reported ORs or HRs of RA-ILD risk factors. They excluded studies with patients who had ILD before their RA diagnosis.

Two reviewers independently assessed the eligibility of the retrieved citations, with disagreements resolved by consensus. Potential eligible citations were further examined through a full-text review. Various data were extracted from eligible studies, including the sample size, ILD diagnosis criteria, and risk factors of incident RA-ILD. When the available information from the publications was incomplete, the reviewers attempted to retrieve it from other sources or by contacting the corresponding authors.

Initially, the researchers identified 3075 studies, 12 of which met the eligibility criteria and were included in the qualitative analysis. These consisted of 3 case-control and 9 cohort studies, with most published within the past 5 years and conducted in the US. The sample sizes ranged from 210 to 30,512, and the RA-ILD incidence rates ranged from 1.8 to 6.7 per 1000 person-years.

The researchers identified 17 RA-ILD risk factors, categorizing those reported in more than 2 studies. These were treatment regimens (glucocorticoids, methotrexate, LEF, biologics), demographics (gender, age, age at RA onset, smoking history), comorbidities (pulmonary, systemic), disease involvement (joint erosion, rheumatoid nodule), Disease Activity Score 28 (DAS28), and laboratory tests (rheumatoid factor, anticitrullinated peptide antibody, C reactive protein, erythrocyte sedimentation rate).

Among the identified risk factors, male gender (relative risk [RR], 1.94; 95% CI, 1.33-2.85; P < .001), age over 60 years (RR, 1.42; 95% CI, 1.05-1.94; P = .02), older age at RA onset (RR, 1.05; 95% CI, 1.01-1.10; P = .02), pulmonary comorbidities (RR, 2.72; 95% CI, 1.24-5.95; P = .01), ever-smoker status (RR, 1.37; 95% CI, 1.09-1.71; P = .006), the presence of rheumatoid nodules (RR, 1.85; 95% CI, 1.36-2.51; P < .001), and treatment with LEF (RR, 1.41; 95% CI, 1.02-1.96; P = .04) were associated with a significantly increased RA-ILD risk.

“Physicians should be aware that patients with RA with the above risk factors are likely to develop RA-ILD and perform close ILD screening during follow-ups so that the patients can be early diagnosed and treated and achieve improved prognosis,” the authors wrote.

Lastly, the researchers acknowledged their limitations, one being that only cohort and nested case-control studies were included; therefore, a limited number of studies were analyzed. Despite their limitations, they expressed confidence in their findings, stressing the importance of early screening.

“Given that pulmonary fibrosis is usually irreversible, it is of significant importance to screen for ILD in high-risk patients to achieve early diagnosis and treatment, leading to a better long-term prognosis,” the authors concluded.

References

1. Yu C, Zhang Y, Jin S, et al. Risk factors for incidence of interstitial lung disease in patients with rheumatoid arthritis: a systematic review and meta-analysis. BMJ Open Respir Res. 2024;11(1):e001817. doi:10.1136/bmjresp-2023-001817

2. Dai Y, Wang W, Yu Y, Hu S. Rheumatoid arthritis-associated interstitial lung disease: an overview of epidemiology, pathogenesis and management. Clin Rheumatol. 2021;40(4):1211-1220. doi:10.1007/s10067-020-05320-z