Pre-treatment non-ictal cephalic allodynia identifies responders to prophylactic treatment of chronic and episodic migraine patients with galcanezumab: A prospective quantitative sensory testing study (NCT04271202)

Abstract

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.

Central generators of migraine and autonomic cephalalgias as targets for personalized pain management: Translational links

“…In this regard, it has been proposed that ictal allodynia has an important impact on the efficacy of triptans (Burstein et al, 2004). Interestingly also, the presence/absence of non‐ictal allodynia has been used in migraineurs to identify responders versus non‐responders to treatment with the monoclonal antibody against CGRP galcanezumab, with nearly 80% accuracy (Ashina et al, 2023).…”

Translation, cross-cultural adaptation and measurement proprieties of the German version of the Allodynia Symptom Checklist (ASC-12)

“…Recent literature links allodynia to dysfunctional analgesic mechanisms and abnormal representation of pain perception [ 39 ], which are associated with migraine chronification [ 40 , 41 ] and observed more prominent during migraine attacks [ 42 ]. Interestingly, the presence of interictal allodynia can identify with 85% of accuracy non-responders of CGRP monoclonal antibodies [ 43 ]. The skin hypersensitivity can be explained by a hypofunction of the descending pain inhibitory system, which modulates the nociceptive transmission, or by a facilitation of the ascending pain system [ 44 ].…”

Mode and site of action of therapies targeting CGRP signaling

“…Clinical studies are still scarce but have shown potential benefits of combination therapy [ 125 , 135 ]. Third, non-responders could have a state of central neuron sensitization, supported by the presence of non-ictal allodynia, that is independent from peripheral activation and that cannot be attenuated by anti-CGRP mAbs [ 136 ]. In clinical practice, presence of non-ictal allodynia seems to be a useful predictor of lack of response to galcanezumab [ 136 ].…”