Short telomere length is associated with accelerated lung disease progression in rheumatoid arthritis-associated...

Shorter leukocyte telomere length (LTL) has been reported in patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) and linked to increased disease severity and mortality in idiopathic pulmonary fibrosis, which shares similarities with RA-ILD. We aimed to evaluate the impact of short LTL on baseline respiratory disease severity, disease progression and survival in patients with RA-ILD.

Patients diagnosed with RA-ILD following multidisciplinary assessment were enrolled in a prospective French observational study. LTL was measured at enrolment using qPCR. Short LTL was defined as age-adjusted LTL <10th percentile. Lung disease progression was defined as death, lung transplantation or functional respiratory decline (absolute decrease in forced vital capacity (FVC) ≥5% predicted or diffusing capacity of the lung for carbon monoxide (D _LCO) ≥10% predicted).

Among 101 patients with RA-ILD, 46% were male, mean±sd age at enrolment was 66±10 years and 43 (43%) had short LTL. Patients with short LTL had lower FVC % predicted (82% versus 93%) and D _LCO % predicted (49% versus 63%) at enrolment, and greater 12-month decline in FVC % predicted and D _LCO % predicted in mixed effects models (-7.7% (95% CI -11.6- -3.8%); p<0.001 and -4.5 (95% CI -7.2- -1.8%); p=0.001, respectively), although transplant-free survival was similar over a median (interquartile range) follow-up of 3.6 (1.8-7.0) years. Lung disease progression was observed within 12 months of enrolment in 33 (33%) patients, more frequently in patients with short LTL (47% versus 22%; univariate p=0.011) and lower FVC at enrolment. Multivariate logistic regression identified lower FVC and short LTL as predictors of 12-month progression (OR 0.97 (95% CI 0.94-1.00); p=0.031 and OR 2.80 (95% CI 0.99-8.29); p=0.056, respectively).

Short LTL is associated with baseline severity and 12-month progression in RA-ILD.