By Pat Anson, PNN Editor

CGRP inhibitors have been one of the biggest innovations in migraine treatment in decades. CGRP stands for calcitonin gene-related peptides, a protein that binds to nerve receptors in the brain and triggers migraine pain. Since 2018, the FDA has approved over half a dozen CGRP inhibitors for migraine prevention and treatment.

The problem with anti-CGRP therapies – besides their high cost – is that they only work for about half the people who take them.

A new test may take some of the guesswork out of CGRP therapy, by predicting with about 80% accuracy which patients will respond to CGRP inhibitors before treatment begins.  In a small study published in the journal Cephalalgia, Harvard Medical School researchers found that most migraine patients with non-ictal cephalic allodynia -- pain sensitivity experienced in-between migraine attacks – did not respond to CGRP treatment. Conversely, most patients without non-ictal cephalic allodynia did respond to CGRP therapy.  

Determining which patients have or don’t have cephalic allodynia is relatively easy, through a novel Quantitative Sensory Testing (QST) algorithm that measures how sensitive patients are to heat, cold and being poked in the skin with a sharp object. The test identified CGRP responders with nearly 80% accuracy and non-responders with nearly 85% accuracy.

“Detection of non-ictal cutaneous allodynia with a simplified paradigm of QST may provide a quick, affordable, non-invasive, and patient-friendly way to prospectively distinguish between responders and non-responders to the prophylactic treatment of migraine with drugs that reduce CGRP signaling,” wrote lead author Rami Burstein, MD, Professor of Anesthesia, Harvard Medical School.

Burstein helped develop the QST test in collaboration with CGRP Diagnostics. The test can be done in about five minutes in a doctor’s office.

“This is all about improving outcomes for people suffering from migraines and so we strongly recommend that all potential anti-CGRP recipients have the test done prior to prescription,” said Mark Hasleton, PhD, CEO of CGRP Diagnostics. 

“This will help provide migraine sufferers with either the best chance for treatment success for likely responders, or to enable rapid transition for likely non-responders to other treatment strategies, thus avoiding the misery of treatment failure. CGRP Diagnostics is currently in discussions with multiple key pharma and payor players in this area, with the expectation that such a test will become a prerequisite prior to anti-CGRP prescription.”

A surprise finding from the study is that cutaneous allodynia may be related to genetic factors that cause pain sensitivity, rather than the frequency or severity of migraines.

“This study unveils the mechanism of physiological response to anti-CGRP therapy and could fundamentally change the anti-CGRP therapy field,” said Iris Grossman, PhD, Founding Scientific Advisor at CGRP Diagnostics. “We now have an objective tool to tailor early and effective therapy to migraine sufferers. This novel test holds the potential for earlier access to anti-CGRP therapy, reduced need for prior treatment failures with generics, and enhanced formulary access. It also enables non-responders to rapidly transition to other treatment strategies, preventing a great deal of suffering and frustration for all.”

A 2020 survey of migraine patients by Health Union found that 52% of those who tried a CGRP therapy switched brands because the treatment didn’t work or because they didn’t like the side effects, such as constipation and weight gain.

CGRP medications are not cheap. Eight doses of Nurtec, the migraine treatment endorsed by Khloe Kardashian, can cost over $1,000 without insurance.

Migraine affects more than 37 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.