Exploring Synergistic Drug Combinations for Vasodilation in Systemic Sclerosis

Recent research presented at the 2025 European Congress of Rheumatology has shed light on the potential benefits of combining different vasodilating drugs (VVD) for managing vasculopathy in systemic sclerosis (SSc). Vasculopathy, a key factor in the development of SSc, involves blood vessel damage and dysfunction. VVD, which promote vasodilation, are an important aspect of treatment strategies. The latest guidelines from the European Alliance of Associations for Rheumatology highlight the importance of exploring synergistic drug combinations and gathering high-quality real-world evidence to optimize patient outcomes.

New data from the congress reveals that most VVD used in clinical trials exhibit anti-fibrotic properties, but results regarding improvements in pulmonary function and the prevention of interstitial lung disease (ILD) progression remain mixed. A post-hoc analysis utilizing the EUSTAR database examined the effects of drugs such as endothelin-receptor antagonists (ERA), phosphodiesterase-5 inhibitors (PDE5i), and prostanoids on disease progression and survival in over 2,000 patients. It found that prostanoids were associated with a reduced risk of ILD progression in patients without digital ulcers—often linked to ILD development—while ERAs appeared protective against symptom worsening, especially in those with more severe vasculopathy.

Interestingly, the analysis noted that DLCO (diffusing capacity of the lungs for carbon monoxide) interacted differently with VVD categories: acting as a risk factor when combined with ERA but serving as a protective factor with prostanoids. The study also found no significant independent impact of VVD on mortality.

Further research presented at the same congress involving more than 4,000 patients evaluated the relationship between VVD, immunosuppressants, and ILD development. While vasodilators like sildenafil and iloprost showed a potentially protective effect against ILD development within one year, immunosuppressants did not demonstrate a significant protective role, highlighting the possible importance of VVD in early disease management.

The findings suggest that the effectiveness of VV drugs may depend on the patient's clinical profile, particularly the presence of digital ulcers, which correlate with disease severity. The evidence underscores the need for further randomized controlled trials to better understand and confirm these preliminary findings.

In conclusion, the research emphasizes that combining vasodilating drugs, especially sildenafil and iloprost, could offer a protective benefit against ILD in systemic sclerosis. Tailoring treatments according to individual patient characteristics holds promise, but more rigorous studies are essential to establish definitive therapeutic strategies.