Author:
Al-Hassany Linda,Karsan Nazia,Lampl Christian,Goadsby Peter J.,MaassenVanDenBrink Antoinette
Abstract
AbstractMigraine is a debilitating disorder, and while the introduction of monoclonal antibodies (mAbs) has led to efficacious and tolerable responses, a substantial number of patients are so-called “non-responders”. We introduce reasons for this insufficient response, including insufficient blockade of Calcitonin Gene-Related Peptide (CGRP) or its receptor. We present a clinical case, i.e. a female migraine patient who mistakenly administered supratherapeutic (three-fold higher) doses of erenumab 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 pharmacokinetic-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 aspects in future trials could optimize healthcare for a larger proportion of migraine patients.
Publisher
Springer Science and Business Media LLC
Subject
Anesthesiology and Pain Medicine,Neurology (clinical),General Medicine
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献