Triple negative patients with SSc-ILD at risk for disease progression

Progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is still possible among patients who are positive for anticentromere antibody (ACA) or anti-RNA polymerase III antibody (ARA), results of a trial have shown.

On the other hand, patients who are negative for ACA, ARA, and antitopoisomerase I antibody (ATA) exhibit a greater progression rate than the overall trial population and must be monitored closely.

Researchers performed a post hoc analysis of the SENSCIS trial (nintedanib vs placebo in SSc-ILD) and analysed the rate of decline in forced vital capacity (FVC) over 52 weeks in the following subsets: (1) positive for ACA; (2) positive for ARA; and (3) negative for ACA, ARA, and ATA.

Among the participants who underwent baseline serological evaluation, 32/549 (5.8 percent) were positive for ACA, 98/528 (18.6 percent) were positive for ARA, and 127/526 (24.1 percent) were negative for ACA, ARA, and ATA. [J Rheumatol 2025;52:914-918]

The adjusted rate of decline in FVC in the placebo arm was ‒31.2 mL/year among participants who were ACA positive and ‒64.7 mL/year among those who were ARA positive. These values were numerically lower than in the overall trial population (‒93.3 mL/year).

In contrast, the rate of decline in FVC was numerically higher among participants who were negative for ACA, ARA, and ATA than the overall trial population, both among those in the placebo arm (‒115.6 vs ‒93.3 mL/year) and those in the nintedanib arm (‒91.8 vs ‒52.4 mL/year).

Triple negative

A retrospective analysis of patients with SSc-ILD at a single centre showed no significant association of neither ACA nor ARA status with change in FVC% predicted per year. However, the decline in FVC was also numerically lower in those who were ACA or ARA positive. [Rheumatology 2023;62:2501-2509]

Furthermore, the Scleroderma Lung Study II, which compared mycophenolate to cyclophosphamide for the treatment of SSc-ILD, found no association between the presence of ARA or ACA and FVC course, although the number of patients who were ACA or ARA positive was small. [Lancet Respir Med 2016;4:708-719; ACR Open Rheumatol 2023;5:547-555]

“Our finding that patients in the SENSCIS trial who were negative for ACA, ARA, and ATA experienced a numerically greater rate of decline in FVC than the overall trial population is noteworthy, as such patients may not receive the same degree of close monitoring and/or aggressive therapy as patients who possess ATA, for example,” the researchers said.

“Such ‘triple negative’ patients may also experience delays in diagnosis of SSc, particularly those with limited cutaneous disease, prolonging the time to initiation of therapy,” they added.

Results of the current study recommend treatment and close monitoring for SSc-ILD progression among patients who were negative for ACA, ARA, and ATA.

“Future studies are needed to determine whether the presence or absence of specific autoantibodies portends an improved response to therapies, as this may facilitate the application of personalized medicine to the treatment of SSc-ILD,” the researchers said.