Modified‐release sildenafil reduces Raynaud's phenomenon attack frequency in limited cutaneous systemic sclerosis

• Published in: Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2011-03, Vol.63 (3), p.775-782
• Main Authors: Herrick, Ariane L., van den Hoogen, Frank, Gabrielli, Armando, Tamimi, Nihad, Reid, Carol, O'Connell, Damian, Vázquez‐Abad, Maria‐Dolores, Denton, Christopher P.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; Cardiology. Vascular system; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - adverse effects; Diseases of the osteoarticular system; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Double-Blind Method; Drug therapy; Female; Humans; Male; Medical research; Medical sciences; Middle Aged; Piperazines - administration & dosage; Piperazines - adverse effects; Purines - administration & dosage; Purines - adverse effects; Raynaud disease; Raynaud Disease - drug therapy; Raynaud Disease - etiology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Scleroderma, Limited - complications; Secondary Prevention; Sildenafil Citrate; Sulfones - administration & dosage; Sulfones - adverse effects; Treatment Outcome; Vasodilator Agents - administration & dosage; Vasodilator Agents - adverse effects
• ISSN: 0004-3591; 2326-5191; 1529-0131; 2326-5205
• DOI: 10.1002/art.30195

Objective To examine the effect of sildenafil in patients with Raynaud's phenomenon (RP) secondary to limited cutaneous systemic sclerosis (lcSSc). Methods In this double‐blind, placebo‐controlled study, 57 patients with RP secondary to lcSSc were randomized to receive modified‐release sildenafil 100 mg once daily for 3 days followed by modified‐release sildenafil 200 mg once daily for 25 days or placebo. The primary assessment was the percentage change in the number of RP attacks per week in the per‐protocol population. Secondary end points included Raynaud's Condition Score, duration of attacks, RP pain score, endothelial dysfunction assessed by a peripheral arterial tonometric (PAT) device, and serum biomarker levels. Results The mean percentage reduction from baseline to day 28 in attacks per week was greater for modified‐release sildenafil than for placebo (−44.0% versus −18.1%, P = 0.034); the mean number of attacks per week improved from 25.0 at baseline to 19.3 after placebo treatment and from 30.5 to 18.7 after modified‐release sildenafil treatment (P = 0.244). Decreases from baseline in Raynaud's Condition Score, duration of attacks, and RP pain score were not significantly different between groups. Mean values and changes from baseline in PAT responses and serum biomarker levels were similar between groups. The most frequent adverse events were headache and dyspepsia; the majority of adverse events were mild or moderate. Conclusion Our findings indicate that modified‐release sildenafil reduced attack frequency in patients with RP secondary to lcSSc and was well tolerated. Modified‐release sildenafil may be a treatment option in this patient population.