title: Combination therapy with Bosentan and Sildenafil improves Raynaud's phenomenon and fosters the recovery of microvascular involvement in systemic sclerosis.
abstract: The aim of this study was to evaluate in systemic sclerosis (SSc) retrospectively the effect of Bosentan and Sildenafil and their combination on Raynaud's phenomenon (RP), function, and capillaroscopic patterns. One hundred and twenty-three SSc patients (mean age ± sd, 57.69 ± 14.07 years) were retrospectively evaluated and divided into two groups according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification score: group 1 score < 10, group 2 score > 10. Each group was divided into three subgroups according to treatment: Bosentan, Sildenafil, and Bosentan + Sildenafil. Nailfold videocapillaroscopy (NVC), Scleroderma Health Assessment Questionnaire (SHAQ) and Raynaud Condition Score (RCS) were performed at baseline and after 3 and 6 months. In Bosentan (29 patients: 12, group 1; 17, group 2), NVC changed significantly in both groups, after 3 and 6 months (p = 0.00439, group 1; p = 0.00035, group 2). In group 1, the "active" and the "late" patterns reduced, and the "aspecific" increased. In group 2, there was a reduction of late patterns, a worsening of SHAQ (p < 0.005) and an improvement of RCS (p = 0.00014). In Sildenafil (63 patients: 35, group 1; 28, group 2), after 3 months, NVC patterns changed significantly in both groups(p = 0.042 group 1, p = 0.00089 group 2). In group 1, the late and early patterns increased, and the aspecific decreased. In group 2, a significant change of NVC pattern was observed also after 6 months (p = 0.00089): the late pattern increased while the active one reduced. After 6 months, SHAQ was significantly reduced in group 1 (p = 0.00027) and in group 2 (p = 0.0043). RCS improved in both groups (p = 0.0042, group 1; p = 0.0016, group 2). Combination therapy (Bosentan + Sildenafil) (31 patients: 14, group 1; 17, group 2) induced significant changes on NVC only in group 1 after 3 (p = 0.00256) and 6 months (p = 0.000349) with a reduction of the late and active patterns and an increase of the early pattern. In both groups, after 6 months, SHAQ (p < 0.05, group 1; p = 0.00049, group 2) and RCS significantly reduced (group 1, p = 0.00024; group 2, p = 0.0021). Patients treated with Bosentan + Sildenafil show a significant improvement of RCS and NVC. This combination therapy may exert a vascular activity achieving an amelioration of the structure of microvasculature in SSc.
authors.affiliation: Department of Experimental and Clinical Medicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy. s.bellandorandone@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Bellando-Randone
authors.affiliation: Department of Experimental and Clinical Medicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy. lepri.gemma@gmail.com.
authors.forename: G
authors.initials: G
authors.lastname: Lepri
authors.affiliation: Department of Experimental and Clinical Medicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Bruni
authors.affiliation: Department of Experimental and Clinical Medicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Blagojevic
authors.affiliation: Department of Experimental and Clinical Medicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Radicati
authors.affiliation: Department of Experimental and Clinical Medicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cometi
authors.affiliation: Department of Translational Medical Sciences, Centre for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: De Paulis
authors.affiliation: Department of Experimental and Clinical Medicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.affiliation: Department of Experimental and Clinical Medicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Guiducci
mesh_terms: D000328:Adult; D000368:Aged; D000077300:Bosentan; D002196:Capillaries / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D020678:Microscopic Angioscopy; D055806:Microvessels / Q000187:drug effects*; D008875:Middle Aged; D009262:Nails / Q000098:blood supply; D011928:Raynaud Disease / Q000188:drug therapy*; D012189:Retrospective Studies; D012595:Scleroderma, Systemic / Q000188:drug therapy*; D000068677:Sildenafil Citrate / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D013449:Sulfonamides; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D000077300:Bosentan
keywords: Bosentan; Microvasculature; Sildenafil; Systemic sclerosis