Recombinant human relaxin in the treatment of scleroderma. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2000 Jun 06;132(11):871-9
Date
06/03/2000Pubmed ID
10836913DOI
10.7326/0003-4819-132-11-200006060-00004Scopus ID
2-s2.0-0034612234 (requires institutional sign-in at Scopus site) 240 CitationsAbstract
BACKGROUND: Relaxin is a pregnancy-related hormone that has tissue remodeling and antifibrotic effects. Systemic sclerosis (scleroderma) is characterized by fibrosis of the skin, vasculature, and internal organs.
OBJECTIVE: To assess the efficacy, safety, and dose-response effect of recombinant human relaxin in patients with scleroderma.
DESIGN: Multicenter, parallel-group, randomized, double-blind, placebo-controlled 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 microg/kg of body weight per 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 Questionnaire, and other measures of scleroderma that reflected fibrosis.
RESULTS: Patients who received 25 microg/kg of recombinant human relaxin per day had significantly lower skin scores than those who received placebo (mean 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 measures, including forced vital capacity, measures of oral aperture and hand extension, functional status, and global assessment. Patients who received 100 microg/kg of relaxin per day did not differ from those who received placebo. Drug-related adverse events included menometrorrhagia, reversible anemia, and complications of the subcutaneous drug administration system (site irritation and local infection).
CONCLUSIONS: Twenty-four weeks of recombinant human relaxin, 25 microg/kg per day, is associated with reduced skin thickening, improved mobility, and improved function in patients with moderate to severe diffuse scleroderma.
Author List
Seibold JR, Korn JH, Simms R, Clements PJ, Moreland LW, Mayes MD, Furst DE, Rothfield N, Steen V, Weisman M, Collier D, Wigley FM, Merkel PA, Csuka ME, Hsu V, Rocco S, Erikson M, Hannigan J, Harkonen WS, Sanders MEAuthor
Mary Ellen Csuka MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Analysis of Variance
Anemia
Dose-Response Relationship, Drug
Double-Blind Method
Drug Eruptions
Exanthema
Female
Humans
Male
Menorrhagia
Middle Aged
Placebos
Recombinant Proteins
Relaxin
Scleroderma, Systemic
