Treating CRPS-Associated Neuropathic Pain With EGF Receptor Inhibition

A single infusion of cetuximab was not associated with relief from therapy-resistant neuropathic pain.

A single infusion of cetuximab, an epidermal growth factor receptor inhibitor (EGFR-I) was not associated with relief from therapy-resistant neuropathic pain, according to a small proof-of-concept trial published in Pain Medicine, although substantial pain reductions were reported by some of the participants.

Preclinical findings, case reports, and a case series have shown relief from neuropathic pain after treatment with EGFR-Is. With this small proof-of-concept randomized, double-blind placebo-controlled trial, investigators sought to assess the therapeutic efficacy of the EGFR-I cetuximab in 14 patients with chronic, severe, therapy-resistant neuropathic pain associated with complex regional pain syndrome or compressed peripheral nerves. Participants were randomly assigned to receive a single infusion of cetuximab or placebo, followed by a single open-label infusion of cetuximab.

Three to 7 days after the single cetuximab infusion, the mean daily average pain score reduction was 1.73 points (90% CI, 0.80-2.66),  a 1.22-point greater reduction compared with the placebo (90% CI, -0.10 to 2.54) but insufficient to provide conclusive statistical evidence of efficacy. Exploratory analyses suggested that pain relief may be greater in the 14 days following blinded infusion of cetuximab compared with placebo. The percentage of participants reporting a ≥50% average pain reduction 3 to 7 days after treatment with cetuximab was 36%, compared with 14% after placebo. The most frequent side effect was grade 1-2 skin rash, reported by 86% of participants.  

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Study investigators conclude that although this small proof-of-concept trial failed to demonstrate cetuximab superiority, the confidence intervals do not rule out a clinically meaningful effect, and the individual responses of patients do indicate that cetuximab may be a treatment option for some patients with neuropathic pain. “The high response rate among treatment-resistant patients, and the magnitude of pain relief seen in those patients who benefitted are encouraging. Repetitive dosing and longer follow-up of larger, homogeneous samples of patients with sufficiently high pain scores at the time of testing of analgesic effect are now warranted in order to determine the benefit-to-side effect ratio of this treatment.”

Merck KGaA funded trial medication, placebo, and the study grant, as well as two external pain experts to review the protocol prior to study start.

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Kersten C, Cameron MG, Bailey AG, et al. Relief of neuropathic pain through epidermal growth factor receptor inhibition: a randomized proof-of-concept trial [published online May 20, 2019]. Pain Med. doi: 10.1093/pm/pnz101