'Quick, Affordable' Test Helps Predict CGRP Response for Migraine

Megan Brooks

February 21, 2023

Testing for nonictal cephalic allodynia can help predict response to the anticalcitonin gene-related peptide (CGRP) galcanezumab (Emgality, Eli Lilly) for patients with migraine, new research suggests.

The ictal phase refers to "sensitization occurring during a time when central trigeminovascular neurons receive massive nociceptive input from active meningeal nociceptors," whereas the nonictal phase refers to "sensitization occurring during a time when central trigeminovascular neurons receive no or subliminal nociceptive input from meningeal nociceptors," investigators note.

In an observational, open-label cohort study, pretreatment nonictal cephalic allodynia identified galcanezumab responders with nearly 80% accuracy, and it identified nonresponders with nearly 85% accuracy.

"Detection of non-ictal allodynia with a simplified paradigm of Quantitative Sensory Testing (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 chronic and high-frequency episodic migraine with drugs that reduce CGRP signalling," Sait Ashina, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, and colleagues write.

The findings were published online February 14 in Cephalalgia.

Immediate Clinical Relevance

Investigator Rami Burstein, PhD, also with Beth Israel Deaconess Medical Center and Harvard Medical School, developed the concept of predicting response to anti-CGRP treatment by testing for the presence or absence of nonictal cephalic allodynia in collaboration with the company CGRP Diagnostics.

In 43 anti-CGRP-naive patients with migraine, the researchers used a simplified QST algorithm to determine the presence/absence of cephalic or extracephalic allodynia during the nonictal phase of migraine ― defined as the period from less than 12 hours after a migraine attack to less than 12 hours before the next attack.

Patients were considered to have allodynia if heat pain thresholds were between 32° C and 40° C, if cold pain thresholds were between 32° C and 20° C, or if the mechanical pain was threshold was <60 g.

Using these strict criteria, pretreatment nonictal cephalic allodynia was a statistically significant predictor of response to anti-CGRP therapy. It was present in 84% of the 19 nonresponders and was absent in 79% of the 24 responders, for an overall accuracy rate of 86% (P < .0001).

Nonictal cephalic allodynia was "consistently" predictive of response for patients with chronic migraine as well as for those with high-frequency episodic migraine, the researchers report.

In contrast, they note that assessing nonictal extracephalic allodynia with QST missed nearly 50% of the patients with allodynia among the nonresponders (accuracy rate of 42%) and added little to the assessment of allodynia among the responders.

Mark Hasleton, PhD, CEO of CGRP Diagnostics, told Medscape Medical News that the study shows it's possible to determine response to anti-CGRP therapy and to prescribe these medications to patients who are most likely to respond.

Hasleton, who was not personally involved with the current study, noted that pretreatment testing for nonictal cephalic allodynia may also allow for earlier prescription of anti-CGRP therapy and potentially dispense without the need for the current trial-and-error approach to prescribing. He noted that if one anti-CGRP fails the patient, it is highly likely that others will also fail.

Given the "very high correlation of the presence of nonictal cephalic allodynia in responders to galcanezumab, our recommendation would be to routinely pretest all potential anti-CGRP candidates prior to prescription," he said.

End of Trial-and-Error Prescribing

Commenting for Medscape Medical News, Shaheen Lakhan, MD, a neurologist and researcher in Boston, Massachusetts, said this research is "very noteworthy, moving us one step closer to predictive, precision medicine and away from the practice of trial-and-error prescribing.

"The trial-and-error approach to migraine management is daunting. These are very costly therapies, and when they don't work, there is continued tremendous suffering and loss of quality of life for patients," said Lakhan, who was not involved in the study.

He added that the failure of drugs to benefit individual patients "may lead to distrust of the healthcare provider" and to the system as a whole, which in turn could lead to less access to care for other conditions or for preventive measures.

"I envision a time when these predictive measures collectively (interictal allodynia, as in this study, plus biobehavioral data) will assist us neurologists in appropriately selecting migraine therapies," Lakhan said.

"Beyond that, we will eventually test new therapies not in cells, animals, and even humans but in silico. In the very near future, we will have solutions tailored to not people suffering a disease but to you ― an individual with a unique genetic, protein, physical, developmental, psychological, and behavioral makeup," he added.

The study was funded in part by Eli Lilly, the National Institutes of Health, and the Anesthesia Department at Beth Israel Deaconess Medical Center. Galcanezumab was provided by Eli Lilly. Disclosures for the investigators are fully listed in the original article. Lakhan has reported no relevant financial relationships.

Cephalalgia. Published online February 14, 2023. Full article

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