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

James R. Seibold, Joseph H. Korn, Robert Simms, Phillip J. Clements, Larry W. Moreland, Maureen D. Mayes, Daniel E. Furst, Naomi Rothfield, Virginia Steen, Michael Weisman, David Collier, Fredrick M. Wigley, Peter A. Merkel, Mary Ellen Csuka, Vivien Hsu, Susan Rocco, Mark Erikson, John Hannigan, W. Scott Harkonen, Martin E. Sanders

Research output: Contribution to journalArticle

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 μg/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 μg/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 μg/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 μg/kg per day, is associated with reduced skin thickening, improved mobility, and improved function in patients with moderate to severe diffuse scleroderma.

Original languageEnglish (US)
Pages (from-to)871-879
Number of pages9
JournalAnnals of internal medicine
Volume132
Issue number11
DOIs
StatePublished - Jun 6 2000

ASJC Scopus subject areas

  • Internal Medicine

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    Seibold, J. R., Korn, J. H., Simms, R., Clements, P. J., Moreland, L. W., Mayes, M. D., Furst, D. E., Rothfield, N., Steen, V., Weisman, M., Collier, D., Wigley, F. M., Merkel, P. A., Csuka, M. E., Hsu, V., Rocco, S., Erikson, M., Hannigan, J., Harkonen, W. S., & Sanders, M. E. (2000). Recombinant human relaxin in the treatment of scleroderma. A randomized, double-blind, placebo-controlled trial. Annals of internal medicine, 132(11), 871-879. https://doi.org/10.7326/0003-4819-132-11-200006060-00004