Seropositivity was strongly associated with ILD risk in this large prospective cohort study.
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Patients with active rheumatoid arthritis (RA) may face an increased risk of clinically apparent interstitial lung disease (ILD), according to the results of a large prospective cohort study presented at the 2018 American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) Annual Meeting in Chicago, Illinois.
Treatment-to-target of remission or low disease activity for RA is known to improve articular outcomes, but the association with ILD is unclear. Previous studies have correlated active RA with ILD, but these were limited by cross-sectional designs with prevalent ILD.
This study aimed to investigate RA disease activity and incident ILD risk. The results were presented at a Concurrent Abstract Session at the ACR/ARHP annual meeting on October 21 by Jeffrey A. Sparks of the Division of Rheumatology, Immunology, and Allergy at Brigham and Women’s Hospital in Boston.
The researchers studied RA disease activity and incident ILD in a prospective cohort study at a single center, from 2003 to 2016. Of the 1281 subjects at baseline, 82.1% were female, 69.6% were seropositive, and mean age was 56 years. All subjects had received a diagnosis of RA according to ACR criteria. Median RA duration was 9 years, and 58.3% of participants had high/moderate disease activity.
For each subject, researchers measured disease activity score with 28 joints and C-reactive protein (DAS28-CRP3) and covariates annually. Subjects had no clinically apparent ILD at baseline, and every clinically indicated chest CT scan was adjudicated by two pulmonologists and one radiologist, with cases defined as consensus agreement with ILD diagnosis.
Researchers used Cox regression to estimate hazard ratios (HR) for ILD by DAS28-CRP3, adjusting for known ILD risk factors such as age, sex, smoking, RA duration, and serostatus.
Next: the findings-and their implications for physicians
During the 13,141 patient-years (median follow-up, 8 years), researchers identified 86 cases of incident clinically apparent ILD. The ILD risk significantly increased across baseline DAS28-CRP3 categories, with HR of 1.00 (reference) for remission, 0.87 for low, 2.31 for moderate, and 2.27 for high. Moderate/high disease activity had HR for ILD of 2.41, as compared with low/remission.
When researchers analyzed the cumulative average updated DAS28-CRP3 with fewer ILD outcomes and shorter follow-up, they found a trend toward significance of active RA increasing ILD risk. Seropositivity was also strongly associated with ILD risk.
Implications for physicians
Given the substantial morbidity and mortality associated with ILD, determining modifiable risk factors is crucial. In this large prospective cohort using adjudicated ILD outcomes, active RA was associated with increased risk of clinically apparent ILD. These results may help physicians identify at-risk patients.
To confirm these findings, replication studies in other prospective cohorts are required. Clinical trials are needed to firmly establish the role of RA treat-to-target approaches and ILD risk, particularly for patients with seropositive RA.
Sparks JA, Doyle T, Huang J, et al. Rheumatoid Arthritis Disease Activity Predicting Incident Clinically-Apparent Interstitial Lung Disease: A Prospective Cohort Study [Abstract 884]. Arthritis Rheumatol. 2018;70(suppl 10). Accessed October 22, 2018.