Lenalidomide for complex regional pain syndrome type 1

Lack of efficacy in a phase II randomized study

Donald C. Manning, Guillermo Alexander, Joseph C. Arezzo, Alyse Cooper, R. Norman Harden, Anne Louise Oaklander, Srinivasa N. Raja, Richard Rauck, Robert Schwartzman

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1366-1376
Number of pages11
JournalJournal of Pain
Volume15
Issue number12
DOIs
StatePublished - Dec 1 2014

Fingerprint

Complex Regional Pain Syndromes
Reflex Sympathetic Dystrophy
Thalidomide
Controlled Clinical Trials
Placebos
Therapeutics
Research
Chronic Pain
lenalidomide
Extremities
Clinical Trials
Cytokines
Pain
Wounds and Injuries
Population

Keywords

  • clinical trial
  • Complex regional pain syndrome
  • cytokines
  • immunomodulation
  • lenalidomide
  • thalidomide

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Neurology
  • Clinical Neurology
  • Medicine(all)

Cite this

Manning, D. C., Alexander, G., Arezzo, J. C., Cooper, A., Harden, R. N., Oaklander, A. L., ... Schwartzman, R. (2014). Lenalidomide for complex regional pain syndrome type 1: Lack of efficacy in a phase II randomized study. Journal of Pain, 15(12), 1366-1376. https://doi.org/10.1016/j.jpain.2014.09.013

Lenalidomide for complex regional pain syndrome type 1 : Lack of efficacy in a phase II randomized study. / Manning, Donald C.; Alexander, Guillermo; Arezzo, Joseph C.; Cooper, Alyse; Harden, R. Norman; Oaklander, Anne Louise; Raja, Srinivasa N.; Rauck, Richard; Schwartzman, Robert.

In: Journal of Pain, Vol. 15, No. 12, 01.12.2014, p. 1366-1376.

Research output: Contribution to journalArticle

Manning, DC, Alexander, G, Arezzo, JC, Cooper, A, Harden, RN, Oaklander, AL, Raja, SN, Rauck, R & Schwartzman, R 2014, 'Lenalidomide for complex regional pain syndrome type 1: Lack of efficacy in a phase II randomized study', Journal of Pain, vol. 15, no. 12, pp. 1366-1376. https://doi.org/10.1016/j.jpain.2014.09.013
Manning, Donald C. ; Alexander, Guillermo ; Arezzo, Joseph C. ; Cooper, Alyse ; Harden, R. Norman ; Oaklander, Anne Louise ; Raja, Srinivasa N. ; Rauck, Richard ; Schwartzman, Robert. / Lenalidomide for complex regional pain syndrome type 1 : Lack of efficacy in a phase II randomized study. In: Journal of Pain. 2014 ; Vol. 15, No. 12. pp. 1366-1376.
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