TY - JOUR

T1 - Pre-treatment non-ictal cephalic allodynia identifies responders to prophylactic treatment of chronic and episodic migraine patients with galcanezumab

T2 - A prospective quantitative sensory testing study (NCT04271202)

AU - Ashina, Sait

AU - Melo-Carrillo, Agustin

AU - Szabo, Edina

AU - Borsook, David

AU - Burstein, Rami

PY - 2023

Y1 - 2023

N2 - BACKGROUND: Migraine is a complex neurological disorder involving generalized abnormalities in processing sensory information. Adopting evidence that central sensitization imposes major hurdles in the treatment of migraine, we hypothesized that it is the non-ictal (rather than ictal) allodynia that may determine the outcome of migraine prevention with peripherally-acting drugs. METHODS: To test this hypothesis, we used Quantitative Sensory Testing to determine whether it is possible to identify a patient's response to prophylactic treatment with galcanezumab based on presence/absence of cephalic and/or extracephalic allodynia during the pre-treatment non-ictal phase of migraine. RESULTS: Using strict criteria for allodynia (heat 32-40°C, cold 32-20°C, mechanical <60 g), we report that (a) the incidence of pre-treatment non-ictal cephalic allodynia was 21% in the 24 responders (>50% decrease in monthly migraine days) and 85% in the 19 non-responders; (b) the incidence of non-ictal extracephalic allodynia distinguishes responders from non-responders less accurately; and that (c) the incidence of non-ictal cephalic allodynia was similar in the chronic migraine and high-frequency episodic migraine groups. CONCLUSIONS: Clinically, the findings suggest that presence/absence of non-ictal allodynia can be used to identify galcanezumab responders with nearly 80% accuracy and galcanezumab non-responders with nearly 85% accuracy. Mechanistically, the presence of non-ictal allodynia (reflecting a state of activity-independent central sensitization) in both chronic migraine and high-frequency episodic migraine patients raises the possibility that the state of non-ictal allodynia may be attributed to physiological properties of central trigeminovascular neurons that are due to the genetic load of the individual patient rather than their migraine frequency.

AB - BACKGROUND: Migraine is a complex neurological disorder involving generalized abnormalities in processing sensory information. Adopting evidence that central sensitization imposes major hurdles in the treatment of migraine, we hypothesized that it is the non-ictal (rather than ictal) allodynia that may determine the outcome of migraine prevention with peripherally-acting drugs. METHODS: To test this hypothesis, we used Quantitative Sensory Testing to determine whether it is possible to identify a patient's response to prophylactic treatment with galcanezumab based on presence/absence of cephalic and/or extracephalic allodynia during the pre-treatment non-ictal phase of migraine. RESULTS: Using strict criteria for allodynia (heat 32-40°C, cold 32-20°C, mechanical <60 g), we report that (a) the incidence of pre-treatment non-ictal cephalic allodynia was 21% in the 24 responders (>50% decrease in monthly migraine days) and 85% in the 19 non-responders; (b) the incidence of non-ictal extracephalic allodynia distinguishes responders from non-responders less accurately; and that (c) the incidence of non-ictal cephalic allodynia was similar in the chronic migraine and high-frequency episodic migraine groups. CONCLUSIONS: Clinically, the findings suggest that presence/absence of non-ictal allodynia can be used to identify galcanezumab responders with nearly 80% accuracy and galcanezumab non-responders with nearly 85% accuracy. Mechanistically, the presence of non-ictal allodynia (reflecting a state of activity-independent central sensitization) in both chronic migraine and high-frequency episodic migraine patients raises the possibility that the state of non-ictal allodynia may be attributed to physiological properties of central trigeminovascular neurons that are due to the genetic load of the individual patient rather than their migraine frequency.

KW - Allodynia

KW - CGRP monoclonal antibodies

KW - galcanezumab

KW - headache

KW - trigeminal

U2 - 10.1177/03331024221147881

DO - 10.1177/03331024221147881

M3 - Journal article

C2 - 36786278

AN - SCOPUS:85148113555

VL - 43

SP - 3331024221147881

JO - Cephalalgia

JF - Cephalalgia

SN - 0800-1952

IS - 3

ER -