A recent study published in Rheumatic and Musculoskeletal Diseases Open reported that nintedanib may help stabilize capillary density in patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) who are at higher risk of disease progression. In contrast, placebo-treated high-risk patients demonstrated numerical reductions in capillary density over a 52-week period.
Nintedanib, an intracellular tyrosine kinase inhibitor, is an established therapy for idiopathic pulmonary fibrosis (IPF). In patients with IPF, it has been shown to slow disease progression by reducing the rate of decline in forced vital capacity (FVC). Although IPF and SSc-associated ILD originate from different initiating factors, both conditions share overlapping pathogenic mechanisms, including fibroblast-to-myofibroblast transformation and excessive extracellular matrix deposition. Experimental studies suggest that nintedanib exerts antifibrotic, anti-inflammatory, and vascular remodeling effects in various preclinical models mimicking SSc and other progressive fibrosing ILDs.
The findings were based on a substudy of the SENSCIS trial, which evaluated nailfold capillaroscopy images at baseline and at week 52 in patients with SSc-ILD. Parameters assessed included capillary density (number of capillaries per millimeter), presence of giant or abnormally shaped capillaries, and percentage of fingers showing microhaemorrhages. The analysis also examined changes in capillary density in relation to baseline risk factors for rapid FVC decline and the occurrence of ILD progression, defined as an absolute decline in FVC percent predicted greater than 5% or death.
Overall, there were no significant differences in nailfold capillaroscopy measurements between the nintedanib and placebo groups after 52 weeks. However, among the 38 patients identified as high risk for rapid FVC decline, mean capillary density decreased numerically in the placebo group but remained stable with nintedanib. Similarly, in the 11 patients who experienced ILD progression, capillary density showed a numerical increase with nintedanib treatment, while remaining unchanged with placebo. In patients without risk factors or disease progression, no notable changes were observed in either group.
These results suggest that nintedanib may have a stabilizing effect on microcirculation in patients with SSc-ILD at risk of disease progression. While the findings are exploratory, they support the potential use of nailfold capillaroscopy as a noninvasive tool to monitor microvascular changes and disease evolution in systemic sclerosis, warranting further investigation in larger, targeted studies.
References
- Smith V, Denton CP, Herrick AL, Ittrich C, Alves M, Cutolo M. Nailfold capillaroscopy in patients with systemic sclerosis-associated interstitial lung disease: a substudy of the SENSCIS trial. RMD Open. 2025 Oct 17;11(4):e005704.
- Distler O, Highland KB, Gahlemann M, Azuma A, Fischer A, Mayes MD, et al. Nintedanib for Systemic Sclerosis–Associated Interstitial Lung Disease. New England Journal of Medicine. 2019 June 27;380(26):2518–28.