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

Abstract

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.

• Authors: J R Seibold, J H Korn, R Simms, P J Clements, L W Moreland, M D Mayes, D E Furst, N Rothfield, V Steen, M Weisman, D Collier, F M Wigley, P A Merkel, M E Csuka, V Hsu, S Rocco, M Erikson, J Hannigan, W S Harkonen, M E Sanders
• Journal: Annals of internal medicine (Ann Intern Med) Vol. 132 Issue 11 Pg. 871-9 (Jun 06 2000) ISSN: 0003-4819 [Print] United States
• PMID: 10836913 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Placebos
• Recombinant Proteins
• Relaxin

Topics

• Adolescent
• Adult
• Aged
• Analysis of Variance
• Anemia (chemically induced)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Eruptions (etiology)
• Exanthema (chemically induced)
• Female
• Humans
• Male
• Menorrhagia (chemically induced)
• Middle Aged
• Placebos
• Recombinant Proteins (administration & dosage, adverse effects)
• Relaxin (administration & dosage, adverse effects)
• Scleroderma, Systemic (drug therapy, pathology)