Pre-Treatment Cephalic Interictal Allodynia Predicts Outcome of Prophylactic Treatment of Chronic and Episodic Migraine Patients with Galcanezumab: A Prospective Quantitative Sensory Testing Study
Sait Ashina1, Agustin Melo-Carrillo2, Edina Szabo3, David Borsook4, Rami Burstein5
1Beth Israel Deaconess Medical Center, Harvard Medical School, 2Anesthesia, Beth Israel Deaconess Medical Center, Harvard Medical School, 3Anesthesia, Boston Children’s Hospital, Harvard Medical School, 4Psychiatry and Radiology, Massachusetts General Hospital, Harvard Medical School, 5Beth Isreal Deacones Medical Center
Objective:
To investigate whether interictal allodynia may determine the migraine state, including the outcome of migraine prevention with galcanezumab.
Background:
Central sensitization imposes major hurdles for migraine treatment. The abnormal perception of pain and its induction by innocuous stimuli depends on enhanced excitability and responsivity of peripheral and central trigeminovascular neurons that feed into conscious perception of headache.
Design/Methods:
Quantitative Sensory testing was used to determine whether it is possible to predict patients’ response to prophylactic treatment with galcanezumab, a monoclonal antibody against calcitonin gene-related peptide, based on presence or absence of cephalic and/or extracephalic allodynia during the pre-treatment interictal phase of migraine. The criteria used for allodynia was as follows: <40oC for heat, >20oC for cold and < 60g for mechanical.
Results:
We found that the incidence of pre-treatment cephalic interictal allodynia was 21% in the 24 responders (>50% decrease in monthly migraine days) and 85% in the 19 non-responders. The incidence of extracephalic interictal allodynia did not distinguish responders from non-responders while the incidence of cephalic interictal allodynia was similar in the chronic migraine and high-frequency episodic migraine groups. The incidence of interictal allodynia was unrelated to the amount of time patients were headache-free before being tested.
Conclusions:
The findings suggest that it is possible and simple to predict galcanezumab responders with nearly 80% accuracy and galcanezumab non-responders with nearly 85% accuracy. One can infer that the establishment of activity-independent central sensitization is unrelated to the frequency of migraine attacks or to the number of hour/days after the termination of the last attack or initiation of the next attack. It is possible that the interictal allodynia may be attributed to peripheral and central molecular, cellular and/or physiological properties of trigeminovascular neurons that are inherent to the genetic load of the individual rather than the pathophysiological state of disease.