A Risk Score to Detect Subclinical Rheumatoid Arthritis-Associated Interstitial Lung Disease

Abstract

Objective: Patients at high risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) would benefit from being identified before the onset of respiratory symptoms; this can be done by screening patients with the use of chest high-resolution computed tomography (HRCT). Our objective was to develop and validate a risk score for patients who have subclinical RA-ILD.

Methods: Our study included a discovery population and a replication population from 2 prospective RA cohorts (ESPOIR and TRANSLATE2, respectively) without pulmonary symptoms who had received chest HRCT scans. All patients were genotyped for MUC5B rs35705950. After multiple logistic regression, a risk score based on independent risk factors for subclinical RA-ILD was developed in the discovery population and tested for validation in the replication population.

Results: The discovery population included 163 patients with RA, and the replication population included 89 patients with RA. The prevalence of subclinical RA-ILD was 19.0% and 16.9%, respectively. In the discovery population, independent risk factors for subclinical RA-ILD were presence of the MUC5B rs35705950 T allele (odds ratio [OR] 3.74 [95% confidence interval (95% CI) 1.37, 10.39]), male sex (OR 3.93 [95% CI 1.40, 11.39]), older age at RA onset (for each year, OR 1.10 [95% CI 1.04, 1.16]), and increased mean Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (for each unit, OR 2.03 [95% CI 1.24, 3.42]). We developed and validated a derived risk score with receiver operating characteristic areas under the curve of 0.82 (95% CI 0.70-0.94) for the discovery population and 0.78 (95% CI 0.65-0.92) for the replication population. Excluding MUC5B rs35705950 from the model provided a lower goodness of fit (likelihood ratio test, P = 0.01).

Conclusion: We developed and validated a risk score that could help identify patients at high risk of subclinical RA-ILD. Our findings support an important contribution of MUC5B rs35705950 to subclinical RA-ILD risk.

Figure 1

Performance of the proposed risk scores for detection of subclinical rheumatoid arthritis–associated interstitial lung disease in the discovery and replication populations. Results are shown as area under the receiver operating characteristic curves (AUCs) (with 95% confidence intervals [95% CIs]) in the full model (including MUC5B rs35705950) (A and B) and in the simplified model (without MUC5B rs35705950) (C and D). Curves labeled “mean all DAS28‐ESR” represent models that used the mean of all Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) values over the follow‐up until chest high‐resolution computed tomography (HRCT) was performed to calculate the risk score. Curves labeled “mean 4 last DAS28‐ESR” represent models that used the mean of the last 4 DAS28‐ESR values available before chest HRCT to calculate the risk score. Curves labeled “mean last DAS28‐ESR” represent models that used mean of the last DAS28‐ESR value before chest HRCT to calculate the risk score.