ab790f10b114a93b9ef81e778eae7b46 jcm-14-07546.pdf 2c7289841e10229695baa33d40aed71a16baefa0 jcm-14-07546.pdf da88ef2ccda1c775bbf84e0c9fae76bac6fd9a51c0b55c0028355f7c28e4a6f6 jcm-14-07546.pdf Title: Macitentan in the Treatment of Digital Ulcers in Patients with Systemic Rheumatic Autoimmune Diseases: A National Multicenter Study of 42 Patients Subject: 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. Keywords: Raynaud’s phenomenon; digital ulcers; systemic autoimmune rheumatic diseases; systemic sclerosis; macitentan; endothelin receptor antagonist; efficacy; safety Author: Miriam Retuerto-Guerrero, Clara Moriano Morales, Ivan Castellvi Barranco, María Hildegarda Godoy Tundido, Clara Méndez Perles, Carlos de la Puente Bujidos, Ana Salome Pareja Martínez, Marta Garijo Bufort, Leyre Riancho Zarrabeitia, Elena Aurrecoechea Aguinaga, Guillermo González Arribas, Esther F. Vicente-Rabaneda, Silvia Montes García, Belén Atienza-Mateo, Vanesa Calvo-Río, Cristina Corrales Selaya, José Andrés Lorenzo Martín and Elvira Díez Álvarez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Fri Oct 24 13:02:16 2025 CEST ModDate: Fri Oct 24 13:04:26 2025 CEST Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 943527 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- LKTHYW+URWPalladioL-Roma Type 1 Custom yes yes yes 92 0 TVFHYC+URWPalladioL-Ital Type 1 Custom yes yes yes 93 0 CYXJUD+URWPalladioL-Bold Type 1 Custom yes yes yes 94 0 IKKWKP+CMSY10 Type 1 Builtin yes yes yes 167 0 IOAOCB+PalatinoLinotype TrueType WinAnsi yes yes no 178 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 211 0 IOAOCB+PalatinoLinotype TrueType WinAnsi yes yes no 186 0 IOAOBP+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 187 0 IOAPOL+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 188 0 IOAOCB+PalatinoLinotype TrueType WinAnsi yes yes no 207 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-04-25 03:12:31 CEST RepresentationInformation: jcm-14-07546.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-04-24 18:10:34 CEST Size: 943527 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 326 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Patients and Methods Children: Item: Title: Statistical Analysis Item: Title: Ethical Concerns Item: Title: Results Children: Item: Title: Previous Therapies and Treatment Regimens Item: Title: Efficacy Evaluation Item: Title: Safety Profile Item: Title: Discussion Item: Title: Conclusions Item: Title: References Info: Title: Macitentan in the Treatment of Digital Ulcers in Patients with Systemic Rheumatic Autoimmune Diseases: A National Multicenter Study of 42 Patients Author: Miriam Retuerto-Guerrero, Clara Moriano Morales, Ivan Castellvi Barranco, María Hildegarda Godoy Tundido, Clara Méndez Perles, Carlos de la Puente Bujidos, Ana Salome Pareja Martínez, Marta Garijo Bufort, Leyre Riancho Zarrabeitia, Elena Aurrecoechea Aguinaga, Guillermo González Arribas, Esther F. Vicente-Rabaneda, Silvia Montes García, Belén Atienza-Mateo, Vanesa Calvo-Río, Cristina Corrales Selaya, José Andrés Lorenzo Martín and Elvira Díez Álvarez Subject: 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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