Revisiting dose-finding of monoclonal antibodies in migraine

We present a clinical case, i.e. a female migraine patient who mistakenly administered supratherapeutic (three-fold higher) doses of e renumab leading to more efficacious clinical responses without any side-effects. This example illustrates that the initial dosages might have been too low, resulting in a remaining undesired increased effect of CGRP. While a capsaicin forearm model has repeatedly been used to evaluate the pharmacoki netic-pharmacodynamic relationship of mAbs, we provide directions to revisit or reconsider dose-finding and dose-ranging of these drugs. These directions include (i) refinement and application of a capsaicin forehead model (instead of a forearm model) to study trigeminovascular activity and improve dosing, and (ii) reconsideration of trial populations. Indeed, the dose-finding studies were mainly performed in relatively young and normal-weight males, while most phase III/IV trials are marked by a high female-to-male ratio, mainly consisting of overweight to obese females. Considering these asp ects in future trials could optimize healthcare for a larger proportion of migraine patients.
Source: The Journal of Headache and Pain - Category: Neurology Source Type: research