Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement: A Randomized, Double-Blind, Placebo-Controlled Trial

Dinesh Khanna, Philip J. Clements, Daniel E. Furst, Joseph H. Korn, Michael Ellman, Naomi Rothfield, Fredrick Wigley, Larry W. Moreland, Richard Silver, Youn H. Kim, Virginia D. Steen, Gary S. Firestein, Arthur F. Kavanaugh, Michael Weisman, Maureen D. Mayes, David Collier, Mary E. Csuka, Robert Simms, Peter A. Merkel, Thomas A. MedsgerMartin E. Sanders, Paul Maranian, James R. Seibold

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1102-1111
Number of pages10
JournalArthritis and Rheumatism
Volume60
Issue number4
DOIs
StatePublished - Apr 2009

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Relaxin
Diffuse Scleroderma
Placebos
Kidney
Skin
Therapeutics
Creatinine
Subcutaneous Infusions
Systemic Scleroderma
Vital Capacity
Skin Diseases
Randomized Controlled Trials
Outcome Assessment (Health Care)
Clinical Trials
Safety
Lung

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

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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 journalArticle

Khanna, D, Clements, PJ, Furst, DE, Korn, JH, Ellman, M, Rothfield, N, Wigley, F, 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, Sanders, ME, Maranian, P & Seibold, JR 2009, 'Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement: A Randomized, Double-Blind, Placebo-Controlled Trial', Arthritis and Rheumatism, vol. 60, no. 4, pp. 1102-1111. https://doi.org/10.1002/art.24380
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. / Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement : A Randomized, Double-Blind, Placebo-Controlled Trial. In: Arthritis and Rheumatism. 2009 ; Vol. 60, No. 4. pp. 1102-1111.
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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.",
author = "Dinesh Khanna and Clements, {Philip J.} and Furst, {Daniel E.} and Korn, {Joseph H.} and Michael Ellman and Naomi Rothfield and Fredrick Wigley and Moreland, {Larry W.} and Richard Silver and Kim, {Youn H.} and Steen, {Virginia D.} and Firestein, {Gary S.} and Kavanaugh, {Arthur F.} and Michael Weisman and Mayes, {Maureen D.} and David Collier and Csuka, {Mary E.} and Robert Simms and Merkel, {Peter A.} and Medsger, {Thomas A.} and Sanders, {Martin E.} and Paul Maranian and Seibold, {James R.}",
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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.

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