MUC5B Promoter Variant and Survival in Rheumatoid Arthritis-Associated Interstitial Lung Disease

Investigate the association between the MUC5B rs35705950 promoter variant and survival in RA-associated interstitial lung disease (RA-ILD). We studied participants in the Veteran Affairs Rheumatoid Arthritis (VARA) registry with validated ILD diagnoses. Participants were followed until death or end of study period. The MUC5B rs35705950 promoter variant was measured using an Infinium genotyping array, assuming autosomal dominant inheritance. Survival and cause of death were determined from VA death records and the National Death Index. Associations of the MUC5B promoter variant with survival were tested in Cox regression models adjusting for potential confounders. Among 263 participants with RA-ILD (mean age 69 years, 95% male, 73% white race, 85% smoking history), the MUC5B promoter variant was present in 33.5%. Mortality rate was similar between those with (12.2/100PY [95% CI: 9.4, 15.8]) and without (11.1/100PY [95% CI: 9.1, 13.5]) the variant. MUC5B status was not significantly associated with survival overall (aHR 0.97 [95% CI: 0.68, 1.37]) or when stratified by ILD pattern (clinical usual interstitial pneumonia [UIP] aHR 0.86 [95% CI: 0.55, 1.35]; clinical non-UIP aHR 1.15 [95% CI: 0.63, 2.09]). Further, MUC5B status was not significantly associated with respiratory-related (aHR 0.83 [95% CI: 0.42, 1.66]) or non-respiratory causes of death (aHR 1.08 [95% CI: 0.72, 1.62]). While associated with RA-ILD risk, the MUC5B promoter variant was not predictive of survival among RA-ILD patients in this multicentre cohort. Further studies are needed to identify other genetic and non-genetic prognostic factors in RA-ILD to inform disease management.