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 noted.
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 nonictal allodynia with a simplified paradigm of Quantitative Sensory Testing (QST) may provide a quick, affordable, noninvasive, and patient-friendly way to prospectively distinguish between responders and nonresponders to the prophylactic treatment of chronic and high-frequency episodic migraine with drugs that reduce CGRP signaling,” Sait Ashina, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, and colleagues wrote.
The findings were published online 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 less than 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 reported.
In contrast, they noted 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, said in an interview 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.
Dr. 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.