Recombinant human relaxin in the treatment of scleroderma - A randomized, double-blind, placebo-controlled trial

Background: Relaxin is a pregnancy-related hormone that has tissue remodeli ng and antifibrotic effects. Systemic sclerosis (scleroderma) is characteri zed by fibrosis of the skin, vasculature, and internal organs. Objective: T o assess the efficacy, safety, and dose-response effect of recombinant huma n relaxin in patients with scleroderma. Design: Multicenter, parallel-group, randomized, double-blind, placebo-cont rolled trial. Setting: Academic referral centers. Patients: 68 patients who had had stable, diffuse scleroderma (moderate to severe) for less than 5 years. Intervention: Recombinant human relaxin. 25 or 100 mu g/kg of body weight p er day, or placebo administered by continuous subcutaneous infusion over 24 weeks. Measurements: Modified Rodnan skin score was the primary efficacy measure. Secondary measurements were pulmonary function, the Health Assessment Quest ionnaire, and other measures of scleroderma that reflected fibrosis. Results: Patients who received 25 mu g/kg of recombinant human relaxin per day had significantly lower skin scores than those who received placebo (me an change, -3.6 at 4 weeks [P = 0.021], -7.5 at 12 weeks [P < 0.001], and - 8.7 at 24 weeks [P = 0.040]). Similar trends were noted in other outcome me asures, including forced vital capacity, measures of oral aperture and hand extension, functional status, and global assessment. Patients who received 100 mu g/kg of relaxin per day did not differ from those who received plac ebo. Drug-related adverse events included menometrorrhagia, reversible anem ia, and complications of the subcutaneous drug administration system (site irritation and local infection). Conclusions: Twenty-four weeks of recombinant human relaxin. 25 mu g/kg per day, is associated with reduced skin thickening, improved mobility, and im proved function in patients with moderate to severe diffuse scleroderma.