Lenalidomide for Complex Regional Pain Syndrome Type 1: Lack of Efficacy in a Phase II Randomized Study

JOURNAL OF PAIN

卷:15

Article

Manning, Donald C.^1,2  Alexander, Guillermo³  Arezzo, Joseph C.⁴  Cooper, Alyse⁵  Harden, R. Norman⁶  Oaklander, Anne Louise^7,8  Raja, Srinivasa N.⁹  Rauck, Richard¹⁰  Schwartzman, Robert³ 

[1] Univ Virginia Hlth Syst, Dept Anesthesiol, Charlottesville, VA USA

[2] Adynxx Inc, San Francisco, CA USA

[3] Drexel Univ, Dept Neurol, Philadelphia, PA 19104 USA

[4] Albert Einstein Coll Med, Dept Neurosci & Neurol, Bronx, NY 10467 USA

[5] Celgene Corp, Summit, NJ USA

[6] Rehabil Inst Chicago, Ctr Pain Studies, Chicago, IL 60611 USA

[7] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[8] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA

[9] Johns Hopkins Univ, Div Pain Med, Baltimore, MD USA

[10] Clin Res Ctr, Salem, NC USA

关键词: Complex regional pain syndrome;    cytokines;    immunomodulation;    lenalidomide;    thalidomide;    clinical trial;   

DOI  :  10.1016/j.jpain.2014.09.013

来源: Elsevier

【 摘 要 】

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. Perspective: 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. (C) 2014 by the American Pain Society

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