Recombinant Human Relaxin in the Treatment of Systemic Sclerosis With Diffuse Cutaneous Involvement A Randomized, Double-Blind, Placebo-Controlled Trial
Recombinant Human Relaxin in the Treatment of Systemic Sclerosis With Diffuse Cutaneous Involvement A Randomized, Double-Blind, Placebo-Controlled Trial
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DOI：
10.1002/art.24380
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发表时间：
2009-04-01
影响因子：
--
通讯作者：
Seibold, James R.
中科院分区：
文献类型：
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作者：
Khanna, Dinesh;Clements, Philip J.;Seibold, James R.
目标。一项重组人松弛素的II期随机对照试验表明，25 μ g/kg/天的剂量对改善皮肤疾病和减少硬皮病（系统性硬化症；SSc）的功能障碍是安全有效的。我们进行了一项大型随机、双盲、安慰剂对照临床试验，比较安慰剂与10 μ g/kg/天和25 μ g/kg/天的重组人松弛素，在稳定、弥漫性、中重度ssc患者中给予24周。年龄在18-70岁的弥漫性皮肤SSc （dcSSc）患者给予重组人松弛素（10 μ g/kg/天或25 μ g/kg/天）或安慰剂，持续皮下输注24周。第28周进行安全随访。主要结局指标，改良罗德曼皮肤厚度评分，在基线和第4、12和24周时，三组之间相似。3组的次要结局如功能障碍相似，而舒张素组的强迫肺活量明显下降。在接受松弛素治疗的7例患者中，在第24周停用两种剂量的松弛素导致肌酐清除率和严重肾脏不良事件（定义为血清肌酐加倍，肾危象或3级或4级原发性高血压）的统计学显著下降，而没有接受安慰剂治疗的患者。重组松弛素在改善皮肤总评分、肺功能或减轻dcSSc患者功能障碍方面没有显著优于安慰剂。此外，松弛素与严重的肾脏不良事件有关，其中大多数发生在停止输注后。如果松弛素用于治疗硬皮病以外的任何疾病，必须密切监测血压和肾功能。
Objective. A phase II randomized controlled trial of recombinant human relaxin suggested that a dosage of 25 mu g/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 mu g/kg/day and 25 mu g/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 mu g/kg/day or 25 mu g/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.