The New Cutting-Edge Treatment for Migraines

The new sexy business – by which I mean “profitable” – in the treatment of chronic migraine is therapy targeted at the calcitonin gene–related peptide receptor. The past few years have brought several of these to market as ongoing maintenance therapy. This looks at a different application – acute migraine. Their proposed unmet need – the slice of patients for whom various triptans are ineffective.

This is a multi-center, randomized, double-blinded, placebo-controlled trial of rimegepant, an orally-administered CGRP antagonist, administered as a single-dose for acute migraine headache of moderate-to-severe intensity. These authors randomized 1,186 patients in a 1:1 ratio, with the primary end point being freedom from pain at 2 hours after the initial dose.

The winner: rimegepant.

Yes, rimegepant is superior to doing nothing at all for your migraine headache.

And just barely – 19.6% response to rimegepant, compared with 12.0% response to placebo.

The clinical value here is virtually negligible. And, helpfully, the authors provided the primary limitation of this trial for you in the text:

“First, the trial did not include an active comparator to rimegepant.”

The authors note in their introduction many patients receiving triptans do not have a response – 34%! This, however, implies 60+% of patients do have a response – far superior to rimegepant. Then, patients also have an array of over-the-counter options including acetaminophen, ibuprofen, and various caffeine-containing combination therapies. Treating moderate-to-severe migraine attacks with placebo borders on – if not crosses into – unethical territory. Even if this therapy didn’t have a dismal response rate, we still need to generalize it one step further to those who are non-responders to triptans to even have an indication – which would then be the proper enrollment criterion for a trial to ensure the same physiologic features making a patient a triptan non-responder weren’t also a CGPR antagonist non-responder.

Now, no one opposes further exploration of alternative, effective treatments for migraine – headaches, particularly migraine headaches, are relatively common presenting complaints in the Emergency Department. While we have effective abortive treatments for such, there is tremendous value in having a wider array of options for use at home, considering the direct and indirect resource costs and human suffering associated with headaches requiring Emergency Department evaluation and treatment.

But this is junk science – an advertorial in a journal continually proving itself to have virtually no worthy editorial standard:

“Biohaven Pharmaceuticals sponsored the trial, supplied the trial agents, reviewed the trial design, collected the data, and performed data management and analysis. The manuscript was written with the assistance of a medical writer funded by Biohaven Pharmaceuticals. All the authors have confidentiality agreements with Biohaven Pharmaceuticals, either as a condition of employment or in their role as consultants.”

Yet another utter embarrassment for the New England Journal of Medicine.

“Rimegepant, an Oral Calcitonin Gene–Related Peptide Receptor Antagonist, for Migraine”

https://www.nejm.org/doi/full/10.1056/NEJMoa1811090

Addendum: There’s a second study, as well, published in The Lancet with similar results. And, furthermore, deep in a non-redacted part of the protocol, the authors share these unpublished Phase 2b trial results. To be taken with a grain of salt, to be sure, but obviously any comparison with an active drug would have looked much worse for rimegepant:

2 thoughts on “The New Cutting-Edge Treatment for Migraines”

    1. Before my time – or likewise they would have incurred my wrath! For what good that does anyone anywhere.

      In the future, genes will be edited on the fly to reduce the minor inconveniences of life.

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