Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement: a randomized, double-blind, placebo-controlled trial.
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.


CONCLUSIONS
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.
Khanna
Dinesh
D
David Geffen School of Medicine, and School of Public Health, University of California, Los Angeles, USA. dkhanna@mednet.ucla.edu
Clements
Philip J
PJ
Furst
Daniel E
DE
Korn
Joseph H
JH
Ellman
Michael
M
Rothfield
Naomi
N
Wigley
Fredrick M
FM
Moreland
Larry W
LW
Silver
Richard
R
Kim
Youn H
YH
Steen
Virginia D
VD
Firestein
Gary S
GS
Kavanaugh
Arthur F
AF
Weisman
Michael
M
Mayes
Maureen D
MD
Collier
David
D
Csuka
Mary E
ME
Simms
Robert
R
Merkel
Peter A
PA
Medsger
Thomas A
TA
Sanders
Martin E
ME
Maranian
Paul
P
Seibold
James R
JR