Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2009 Apr;60(4):1102-11
Date
04/01/2009Pubmed ID
19333948Pubmed Central ID
PMC3711466DOI
10.1002/art.24380Scopus ID
2-s2.0-65249109216 (requires institutional sign-in at Scopus site) 115 CitationsAbstract
OBJECTIVE: A phase II randomized controlled trial of recombinant human relaxin suggested that a dosage of 25 microg/kg/day was safe and clinically effective in improving skin disease and reducing functional disability in scleroderma (systemic sclerosis; SSc). We undertook a large randomized, double-blind, placebo-controlled clinical trial to compare placebo with 10 microg/kg/day and 25 microg/kg/day recombinant human relaxin, given for 24 weeks in patients with stable, diffuse, moderate-to-severe SSc.
METHODS: Men and women ages 18-70 years with diffuse cutaneous SSc (dcSSc) were administered recombinant human relaxin (10 microg/kg/day or 25 microg/kg/day) or placebo for 24 weeks as a continuous subcutaneous infusion. There was a followup safety visit at week 28.
RESULTS: The primary outcome measure, the modified Rodnan skin thickness score, was similar among the 3 groups at baseline and at weeks 4, 12, and 24. Secondary outcomes such as functional disability were similar in all 3 groups, while the forced vital capacity decreased significantly in the relaxin groups. The discontinuation of both doses of relaxin at week 24 led to statistically significant declines in creatinine clearance and serious renal adverse events (defined as doubling of serum creatinine, renal crisis, or grade 3 or 4 essential hypertension) in 7 patients who had received relaxin therapy but in none who had received placebo.
CONCLUSION: Recombinant relaxin was not significantly better than placebo in improving the total skin score or pulmonary function or in reducing functional disability in patients with dcSSc. In addition, relaxin was associated with serious renal adverse events, the majority of which occurred after stopping the infusion. If relaxin is used therapeutically for any conditions other than scleroderma, close monitoring of blood pressure and renal function must be performed.
Author List
Khanna D, Clements PJ, Furst DE, Korn JH, Ellman M, Rothfield N, Wigley FM, Moreland LW, Silver R, Kim YH, Steen VD, Firestein GS, Kavanaugh AF, Weisman M, Mayes MD, Collier D, Csuka ME, Simms R, Merkel PA, Medsger TA Jr, Sanders ME, Maranian P, Seibold JR, Relaxin Investigators and the Scleroderma Clinical Trials ConsortiumAuthor
Mary Ellen Csuka MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultCreatinine
Dose-Response Relationship, Drug
Double-Blind Method
Female
Humans
Infusions, Subcutaneous
Male
Middle Aged
Placebos
Recombinant Proteins
Relaxin
Scleroderma, Systemic
Skin
Substance Withdrawal Syndrome
Treatment Failure
Vital Capacity
