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Conventional wisdom holds that the longer a patient has rheumatoid arthritis (RA), the greater their risk for interstitial lung disease (ILD), but a recent analysis from a long-term study has provided fresh evidence that people with early RA also are at significant risk for ILD and identified risk factors that make them vulnerable.

The cross-sectional analysis of the study of inflammatory arthritis and ILD in early RA (SAIL-RA), published online on October 14, 2025, in The Lancet Rheumatology, found that 11% of patients with early RA had RA-associated ILD (RA-ILD). At the highest risk were patients with moderate or high RA disease activity and aged 60 years or older.

“Ours is one of the largest prospective studies focused on prevalence of ILD in early RA,” senior study author Jeffrey Sparks, MD, MMSc, director of immuno-oncology and autoimmunity at Harvard Medical School in Boston, told Medscape Medical News. “Most previous studies were either retrospective or enrolled patients with any RA duration. We found several risk factors and also applied previously proposed strategies for screening within this population.”

The study underscores the importance of managing a patient’s RA in all stages of the disease, said Scott Matson, MD, an assistant professor of pulmonary, critical care, and sleep medicine at The University of Kansas Medical Center in Kansas City, Kansas.

“It’s a very reasonable initial clinical target to say — whether it’s early or late RA — the most important first feature in terms of changing that patient’s risk for ILD is making sure their RA is as well-controlled as possible,” he said. “Probably that means increasing the medicines used until the that patient has low disease activity. That’s probably the most important thing we can take away from a clinical perspective.”

SAIL-RA included 191 patients recruited over 7 years up until February 2024. A total of 74% were women, and 68% tested positive for rheumatoid factor. Their median duration of RA was 9.5 months. Most patients (84%) were White individuals, and 62% had never smoked. Among the 172 patients who had high-resolution CT chest imaging, 84% had no sign of parenchymal lung disease and served as the comparator group for the main study analysis.

“A simple strategy of having two or more risk factors — male sex, age 60+ years or moderate/high disease activity — was associated with ILD and may be a population to consider screening with high-resolution chest CT scan,” Sparks said.

Disease Activity Measure

The study found that a strong determinant of RA-ILD was a Disease Activity Score using 28 joints with erythrocyte sedimentation rate ≥ 3.2. This risk factor was associated with sevenfold greater odds for RA-ILD vs remission or low disease activity, with an adjusted odds ratio ranging from 1.95 to 25.13. Moderate or high disease activity carried 3.6-fold greater odds for parenchymal lung disease vs low or no disease activity.

Sparks acknowledged that previous studies have made a connection between male sex, older age, and moderate or high disease activity and a higher risk for RA-ILD. “However,” he said, “few of them were prospective and performed in early RA.”

The SAIL-RA researchers’ analysis did not identify some associations with ILD, such as seropositive RA, but Sparks noted that “the study may have been too small to detect an association.”

Analysis of Screening Strategies

The study also presented the first external validation and use in patients with early RA of six proposed screening strategies for RA-ILD. There was high sensitivity and poor specificity when a cutoff of at least one risk factor was used in the strategies derived from the eligibility criteria for the ongoing ANCHOR-RA (autoantibodies, nonarticular manifestations of RA) study, risk factors suggested by the 2023 American College of Rheumatology (ACR) — American College of Chest Physicians (CHEST) screening guidelines, and the identical risk factors assessed in both the ESPOIR (evaluation and monitoring of recent undifferentiated polyarthritis) and the SAIL-RA cohorts.

However, raising the cutoff to two risk factors or more modestly reduced the sensitivity and modestly improved the specificity for the ANCHOR-RA and 2023 ACR-CHEST strategies.

Strategies that had low sensitivity and high specificity were the five-point cutoff of the four-factor risk score proposed in 2023, the seven-point cutoff of the Spanish Society of Rheumatology-Spanish Society of Pulmonology and Thoracic Surgery criteria, and the Paulin criteria. The ESPOIR/SAIL-RA criteria had the highest odds ratio per factor, followed by the ANCHOR-RA and ACR–CHEST criteria.

Enrollment and follow-up in SAIL-RA is ongoing, Sparks said. He added that future trials should investigate how medications may alter ILD risk and establish an optimal treatment for ILD once it’s diagnosed.

Focus on Early RA

The SAIL-RA analysis is noteworthy because it focused on a population with early RA, Matson said. The cohort’s 11% incidence of ILD in early RA was “more than I would have expected,” he said, but it’s also lower than rates reported in studies across all patients with RA, which have ranged from 15.3% in a 2022 population-based cohort study to 21.4% in a recent systematic review.

Without studies like SAIL-RA, clinicians have been unsure of the rates of ILD in recently diagnosed patients with RA, he said. “We’ve also been guessing somewhat about what’s the best way to enrich populations for screening, and how do we best identify those patients who are at greatest risk for having interstitial lung disease,” Matson added.

Future research needs to follow-up with these study cohorts to determine how many of them develop ILD over time and whether the risk factors identified in the SAIL-RA study, such as high disease activity, are associated with progression or worsening of lung disease, he said.

Sparks reported receiving research support from Bristol-Myers Squibb and Sonoma Biotherapeutics and serving as a consultant for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Johnson & Johnson, Merck, MustangBio, Optum, Pfizer, Sana, Sobi, and ReCor unrelated to this work. Some other authors reported a variety of financial relationships with pharmaceutical companies, included those that market drugs to treat RA or ILD. Matson reported serving as a consultant and advisory board member for Boehringer Ingelheim.

Richard Mark Kirkner is a medical journalist based in Philadelphia.