Outcomes in Systemic Sclerosis-Associated Interstitial Lung Disease Based on Serological Profiles With a Focus on Anticentromere and Anti-RNA Polymerase III Antibodies.

Abstract

We aimed to compare the progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) based on serological status. In a posthoc analysis of the SENSCIS trial (nintedanib vs placebo in SSc-ILD; ClinicalTrials.gov: NCT02597933), we analyzed the rate of decline in forced vital capacity (FVC) over 52 weeks in 3 subsets: (1) positive for anticentromere antibody (ACA), (2) positive for anti-RNA polymerase III antibody (ARA), and (3) negative for ACA, ARA, and antitopoisomerase I antibody (ATA). Among study participants who underwent baseline serological evaluation, 32/549 (5.8%) were ACA positive, 98/528 (18.6%) were ARA positive, and 127/526 (24.1%) were negative for ACA, ARA, and ATA. Among the serological subsets of interest, in the placebo arm, the adjusted rate (standard error) of decline in FVC was -31.2 (41.5) mL/year among participants who were positive for ACA and -64.7 (35.1) mL/year among participants who were positive for ARA, numerically lower than in the overall SENSCIS trial population (-93.3 [13.5] mL/yr). However, participants who were negative for ACA, ARA, and ATA experienced a numerically greater rate of decline in FVC than the overall trial population, both in those randomized to placebo (-115.6 [35.4] mL/yr vs -93.3 [13.5] mL/yr) and those randomized to nintedanib (-91.8 [34.3] mL/yr vs -52.4 [13.8] mL/yr). These analyses of data from the SENSCIS trial suggest that patients with SSc-ILD who are ACA positive or ARA positive can experience progression of SSc-ILD. Patients negative for ACA, ARA, and ATA had a higher rate of progression than the overall trial population and should be monitored closely.