Thursday, February 24, 2011

Botox Ineffective for Chronic Migraine?

Briefly Noted As announced in a Pain-Topics UPDATE [here] last November 2010, Allergan Inc. received FDA approval for Botox® (onabotulinumtoxinA) as preventative therapy for chronic migraine, and the drug also was licensed for this indication in the UK. However, a new report in Drug and Therapeutics Bulletin — or DTB, a publication of the British Medical Journal Group — suggests that the published evidence for Botox's effectiveness as a treatment for chronic migraine is limited and unconvincing [abstract here].

According to an added report in Medical News Today [online here], Botox (a form of botulinum toxin A) treatment requires up to 39 injections into head and neck muscles and must be repeated every 12 weeks for maximum clinical effectiveness. Its mode of action in preventing chronic migraine has not been clearly established, but it appears distinct from Botox's well known paralyzing effect on muscles. The news article also notes that each treatment with Botox for chronic migraine costs around £276 ($450 USD). Importantly, Botox may lead to worsening of headache symptoms in around 10% of those treated, with a similar proportion developing itching, rash, pain, stiffness, and muscles spasms. Rarely, Botox can prompt anaphylactic shock and, despite screening and control procedures, the possibility of transmitting an infection with Botox cannot be ruled out entirely, since the drug contains human serum albumin, according to the article.

The UK's drugs regulator — Medicines and Healthcare products Regulatory Agency (MHRA), comparable to the U.S. FDA — believed that Botox offered a "unique approach" for migraine treatments, which avoided the systemic side effects of many pharmacotherapies and had a favorable safety profile. The efficacy of Botox was expected to improve over time with repeated treatment sessions. Approval of Botox for migraine in the U.S. and UK was supported by the manufacturer’s PREEMPT — Phase III REsearch Evaluating Migraine Prophylaxis Therapy — program, consisting of 2 large, double-blind, placebo-controlled clinical trials involving 1,384 adults from 122 study sites in North America and Europe. The PREEMPT studies were published in the July 2010 print issue of Cephalalgia [abstract here].

However, the DTB article notes that some headache specialists fault the evidence, claiming that the diagnosis of chronic migraine used in the trials was incorrect, since almost two-thirds of trial participants had been overusing pharmacologic headache treatments. Medication overuse headache, or MOH — in which headache treatments themselves cause rather than relieve headache — would rule out the diagnosis of chronic migraine. "These discrepancies and the limited evidence of benefit make it difficult for us to see a place for botulinum toxin A as treatment for chronic migraine," concludes the article.