Background/Purpose: Long-term outcomes following a diagnosis of rheumatoid arthritis associated interstitial lung disease (RA-ILD) are poor, with a median survival estimated between 3 to 8 years. Despite the profound impact on survival, relatively few prognostic factors are known in RA-ILD. More severe pulmonary disease is associated with reduced survival, but little is understood regarding the contribution of RA disease activity to long-term outcomes in RA-ILD. We aimed to determine whether RA disease activity and functional status, as measured by DAS28-ESR and MDHAQ, were independently associated with survival in RA-ILD.

Methods: We performed a cohort study of patients with RA-ILD nested within a multicenter, prospective RA cohort (Veteran Affairs Rheumatoid Arthritis Registry) that contained patient data from 2003-2019. RA was diagnosed by a rheumatologist and fulfilled ACR criteria while ILD diagnoses were validated through detailed medical record confirmation (clinical diagnoses and corresponding dates, imaging findings, lung biopsy and pulmonary function [FVC and DLCO %-predicted] results). Demographics, seropositivity, RA disease duration, and RA medications were collected from the registry and linked administrative data. RA disease activity (DAS28-ESR) and functional status (MDHAQ) were collected longitudinally through routine care. Death was ascertained through linkage with administrative records and the National Death Index. Multivariable Cox regression models assessed the independent associations of RA disease activity and ILD severity with survival adjusting for age, sex, smoking status, and DMARDs.

Results: Patients with RA-ILD (n=227) had mean (SD) age of 69 (9) years, were 93% male, 75% white, frequently had a smoking history (85%), and a mean DAS28-ESR of 4.0 (1.3), MDHAQ of 1.0 (0.6), FVC % predicted of 77.2 (17.9), and DLCO % predicted of 60.2 (21.9). After RA-ILD diagnosis, the median survival was 8.5 years. Over 1,073 person-years of follow-up, 108 deaths occurred with respiratory disease being the leading cause of death (28% of deaths). When examined in separate models, DAS28-ESR, MDHAQ, and pulmonary (FVC and DLCO % predicted) measures of severity were independently associated with survival (Figure 1A-D). The association between DAS28-ESR (per 1-unit HR 1.22 [95% CI 1.04-1.43]) and MDHAQ (per 1-unit HR 1.89 [95% CI 1.33-2.69]) with mortality persisted after adjusting for FVC % predicted. When assessing RA disease activity and pulmonary severity together, moderate/high RA disease activity or impaired FVC (< 80% predicted) alone were associated with >3-fold higher risk of death compared to those with remission/low disease activity and normal FVC (Figure 2). The combination of moderate/high disease activity and impaired FVC carried the highest risk of death (HR 4.49 [95% CI 1.72-11.71];Figure 2).

Conclusion: Among patients with RA-ILD, more severe RA disease activity and impaired functional status were associated with poorer survival independent of ILD severity. To optimize long-term outcomes in RA-ILD, treatment should be targeted at both controlling the disease activity in RA and pulmonary disease manifestations.

Figure 1. Adjusted Survival Curves in RA-ILD by Disease Activity, Functional Status, and Pulmonary Function Test Categories

Figure 2. Survival in RA-ILD by Combined Disease Activity and Forced Vital Capacity Classification.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dont-forget-about-the-arthritis-in-ra-ild-impact-of-pulmonary-and-ra-disease-severity-on-survival/