Abstract
Objective. A phase II randomized controlled trial of recombinant human relaxin suggested that a dosage of 25 μg/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, placebocontrolled clinical trial to compare placebo with 10 μg/kg/day and 25 μg/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 μg/kg/day or 25 μg/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 mod- ified 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 dis- continuation 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 signif- icantly 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 pres- sure and renal function must be performed.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1102-1111 |
| Number of pages | 10 |
| Journal | Arthritis and Rheumatism |
| Volume | 60 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2009 |
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ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Rheumatology
- Pharmacology (medical)
Cite this
Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement : A Randomized, Double-Blind, Placebo-Controlled Trial. / Khanna, Dinesh; Clements, Philip J.; Furst, Daniel E.; Korn, Joseph H.; Ellman, Michael; Rothfield, Naomi; Wigley, Fredrick; Moreland, Larry W.; Silver, Richard; Kim, Youn H.; Steen, Virginia D.; Firestein, Gary S.; Kavanaugh, Arthur F.; Weisman, Michael; Mayes, Maureen D.; Collier, David; Csuka, Mary E.; Simms, Robert; Merkel, Peter A.; Medsger, Thomas A.; Sanders, Martin E.; Maranian, Paul; Seibold, James R.
In: Arthritis and Rheumatism, Vol. 60, No. 4, 04.2009, p. 1102-1111.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement
T2 - A Randomized, Double-Blind, Placebo-Controlled Trial
AU - Khanna, Dinesh
AU - Clements, Philip J.
AU - Furst, Daniel E.
AU - Korn, Joseph H.
AU - Ellman, Michael
AU - Rothfield, Naomi
AU - Wigley, Fredrick
AU - Moreland, Larry W.
AU - Silver, Richard
AU - Kim, Youn H.
AU - Steen, Virginia D.
AU - Firestein, Gary S.
AU - Kavanaugh, Arthur F.
AU - Weisman, Michael
AU - Mayes, Maureen D.
AU - Collier, David
AU - Csuka, Mary E.
AU - Simms, Robert
AU - Merkel, Peter A.
AU - Medsger, Thomas A.
AU - Sanders, Martin E.
AU - Maranian, Paul
AU - Seibold, James R.
PY - 2009/4
Y1 - 2009/4
N2 - Objective. A phase II randomized controlled trial of recombinant human relaxin suggested that a dosage of 25 μg/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, placebocontrolled clinical trial to compare placebo with 10 μg/kg/day and 25 μg/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 μg/kg/day or 25 μg/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 mod- ified 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 dis- continuation 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 signif- icantly 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 pres- sure and renal function must be performed.
AB - Objective. A phase II randomized controlled trial of recombinant human relaxin suggested that a dosage of 25 μg/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, placebocontrolled clinical trial to compare placebo with 10 μg/kg/day and 25 μg/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 μg/kg/day or 25 μg/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 mod- ified 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 dis- continuation 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 signif- icantly 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 pres- sure and renal function must be performed.
UR - http://www.scopus.com/inward/record.url?scp=65249109216&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65249109216&partnerID=8YFLogxK
U2 - 10.1002/art.24380
DO - 10.1002/art.24380
M3 - Article
C2 - 19333948
AN - SCOPUS:65249109216
VL - 60
SP - 1102
EP - 1111
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
SN - 2326-5191
IS - 4
ER -