{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:02:31Z","timestamp":1790974951440,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,3,30]],"date-time":"2009-03-30T00:00:00Z","timestamp":1238371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>A phase II randomized controlled trial of recombinant human relaxin suggested that a dosage of 25 \u03bcg\/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\u2010blind, placebo\u2010controlled clinical trial to compare placebo with 10 \u03bcg\/kg\/day and 25 \u03bcg\/kg\/day recombinant human relaxin, given for 24 weeks in patients with stable, diffuse, moderate\u2010to\u2010severe SSc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Men and women ages 18\u201370 years with diffuse cutaneous SSc (dcSSc) were administered recombinant human relaxin (10 \u03bcg\/kg\/day or 25 \u03bcg\/kg\/day) or placebo for 24 weeks as a continuous subcutaneous infusion. There was a followup safety visit at week 28.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.24380","type":"journal-article","created":{"date-parts":[[2009,3,31]],"date-time":"2009-03-31T01:45:08Z","timestamp":1238463908000},"page":"1102-1111","source":"Crossref","is-referenced-by-count":135,"title":["Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement: A randomized, double\u2010blind, placebo\u2010controlled trial"],"prefix":"10.1002","volume":"60","author":[{"given":"Dinesh","family":"Khanna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Clements","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Furst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph H.","family":"Korn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ellman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Rothfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrick M.","family":"Wigley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry W.","family":"Moreland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Silver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youn H.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia D.","family":"Steen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary S.","family":"Firestein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur F.","family":"Kavanaugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Weisman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen D.","family":"Mayes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Collier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Csuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Simms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Merkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Thomas A.","family":"Medsger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin E.","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Maranian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Seibold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,3,30]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000264"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)87000-4"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12616665"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12365206"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-132-11-200006060-00004"},{"key":"e_1_2_8_7_2","first-page":"302","article-title":"Safety and pharmacokinetics of recombinant human relaxin in systemic sclerosis","volume":"25","author":"Seibold JR","year":"1998","journal-title":"J Rheumatol"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230510"},{"key":"e_1_2_8_9_2","first-page":"1892","article-title":"Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies","volume":"20","author":"Clements PJ","year":"1993","journal-title":"J Rheumatol"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005650-199206000-00002"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230202"},{"key":"e_1_2_8_12_2","first-page":"466","article-title":"Does incorporation of aids and devices make a difference in the score of the health assessment questionnaire\u2010disability index? Analysis from a scleroderma clinical trial","volume":"35","author":"Khanna D","year":"2008","journal-title":"J Rheumatol"},{"key":"e_1_2_8_13_2","first-page":"832","article-title":"Responsiveness of the SF\u201036 and the Health Assessment Questionnaire Disability Index in a systemic sclerosis clinical trial","volume":"32","author":"Khanna D","year":"2005","journal-title":"J Rheumatol"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kem009"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-199711000-00014"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.050187"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22289"},{"issue":"9","key":"e_1_2_8_18_2","first-page":"S283","article-title":"Performance of the modified Rodnan skin score in clinical trials of scleroderma","volume":"52","author":"Merkel PA","year":"2005","journal-title":"Arthritis Rheum"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199906)42:6<1194::AID-ANR16>3.0.CO;2-7"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsgi.2004.05.002"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780370110"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-6543-y"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/14.3.800"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod66.6.1743"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2005.23880.x"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.49.4.577"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00384.x"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1282.028"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-005-6187-x"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.24380","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.24380","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T12:11:30Z","timestamp":1696680690000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.24380"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3,30]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,4]]}},"alternative-id":["10.1002\/art.24380"],"URL":"https:\/\/doi.org\/10.1002\/art.24380","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3,30]]}}}