Department of Anesthesiology, University of Virginia Health System, Charlottesville, Virginia; Adynxx Inc, San Francisco, California.
Department of Neurology, Drexel University, Philadelphia, Pennsylvania.
J Pain. 2014 Dec;15(12):1366-76. doi: 10.1016/j.jpain.2014.09.013. Epub 2014 Oct 2.
Complex regional pain syndrome (CRPS) is a potentially debilitating chronic pain syndrome with a poorly understood but likely neuroimmune/multifactorial pathophysiology associated with axonal injury. Based on the potential contribution of proinflammatory cytokines to CRPS pathogenesis and prior research with thalidomide, we investigated lenalidomide, a thalidomide derivative, for CRPS treatment. We conducted a phase II, randomized, double-blind, placebo-controlled study to evaluate the efficacy of oral lenalidomide 10 mg once daily in consenting patients with unilateral or bilateral CRPS type 1. The study comprised 12 weeks of treatment followed by a long-term extension. The primary efficacy outcome was reduced pain in the index limb, defined as ≥30% improvement from baseline using an 11-point numeric rating scale. One hundred eighty-four subjects enrolled. The primary endpoint was not met because equal proportions of treated (16.1%) and control (16.1%) subjects achieved the outcome; however, lenalidomide was well tolerated, with no evidence of neuropathy or major adverse effects. This study is the largest controlled, blinded clinical trial in subjects with chronic CRPS using the Budapest research criteria. It demonstrates the feasibility of conducting high-quality clinical trials in CRPS type 1 and provides considerations for designing future trials.
This article reports an adequately powered, controlled clinical trial in subjects with CRPS. Treatment and placebo were equally effective, but the study demonstrated that lenalidomide treatment is feasible in this population. The study provides examples to consider in designing future CRPS trials.
复杂区域疼痛综合征（CRPS）是一种潜在使人衰弱的慢性疼痛综合征，其发病机制尚不完全清楚，但可能与轴突损伤有关的神经免疫/多因素病理生理学有关。基于促炎细胞因子对 CRPS 发病机制的潜在贡献以及沙利度胺的先前研究，我们研究了来那度胺，一种沙利度胺衍生物，用于治疗 CRPS。我们进行了一项 II 期、随机、双盲、安慰剂对照研究，以评估每日口服来那度胺 10mg 对单侧或双侧 CRPS 1 型患者的疗效。该研究包括 12 周的治疗期和随后的长期扩展期。主要疗效终点是指数肢体疼痛减轻，定义为使用 11 点数字评分量表基线至少改善 30%。184 名受试者入组。主要终点未达到，因为接受治疗（16.1%）和对照组（16.1%）的受试者比例相等达到了该结果；然而，来那度胺耐受性良好，没有神经病变或重大不良事件的证据。这项研究是使用布达佩斯研究标准在慢性 CRPS 受试者中进行的最大规模的对照、盲法临床试验。它证明了在 CRPS 1 型中进行高质量临床试验的可行性，并为设计未来的试验提供了考虑因素。
本文报告了一项针对 CRPS 患者的充分效力、对照临床试验。治疗组和安慰剂组的疗效相当，但该研究表明，来那度胺治疗在该人群中是可行的。该研究为设计未来的 CRPS 试验提供了一些考虑因素。
