Macitentan in the Treatment of Digital Ulcers in Patients with Systemic Rheumatic Autoimmune Diseases: A National Multicenter Study of 42 Patients

TL;DR

Macitentan effectively heals digital ulcers in autoimmune disease patients, with gastrointestinal issues and higher ulcer counts predicting poorer outcomes.

Contribution

Demonstrates macitentan's efficacy and safety in treating refractory digital ulcers in systemic rheumatic autoimmune diseases.

Findings

Macitentan achieved 82.9% complete ulcer healing in 3 months.

Gastrointestinal involvement and higher baseline ulcers predicted poorer response in systemic sclerosis patients.

Adverse events were rare and did not lead to treatment discontinuation.

Abstract

Objective: To evaluate the real-world safety and efficacy of macitentan (MACI) in patients with systemic autoimmune rheumatic diseases (SARDs) and refractory digital ulcers (DUs). Methods: We conducted a retrospective observational study of 42 patients treated with MACI (10 mg/day) on a compassionate-use basis across Spanish reference hospitals. Given the cohort’s heterogeneity, a two-step analysis was performed: a global assessment of all patients, followed by a subgroup analysis restricted to those with systemic sclerosis (SSc) or fulfilling very early SSc (VEDOSS) criteria to explore predictors of response. Efficacy was defined as complete healing, partial response, or a lack of response based on physician assessment. Safety was evaluated through analysis of adverse events. Results: In the global cohort, MACI demonstrated a high rate of complete ulcer healing (82.9%) at the 3-month follow-up, with a significant reduction in median ulcer count (p < 0.001). Subgroup analysis within the SSc/VEDOSS cohort (n = 36) revealed that the presence of gastrointestinal involvement (GI) and a higher baseline DUs were significant predictors of a poorer therapeutic response (p = 0.022 and p = 0.028). The drug was well-tolerated; adverse events were infrequent and rarely led to treatment discontinuation. Conclusions: In this real-world refractory population, MACI was associated with rapid DU healing and a favorable safety profile. GI and higher ulcer burden predicted diminished treatment response in SSc patients. These results support the use of MACI as a valuable therapeutic option for severe digital vasculopathy in SARDs, although further prospective studies are warranted to confirm these observations.

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