European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention

DOI: https://doi.org/10.1186/s10194-018-0955-y

Abstract-Summary Monoclonal antibodies acting on the calcitonin gene-related peptide or on its recep- tor are new drugs to prevent migraine.

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4 Treatment

Four monoclonal antibodies have been developed: one targeting the calcitonin gene-related peptide receptor (erenumab) and three targeting the calcitonin gene- related peptide (eptinezumab, fremanezumab, and galcanezumab).

The aim of this document by the European Headache Federation (EHF) is to provide an evidence-based and expert-based guideline on the use of the monoclonal antibodies acting on the calcitonin gene-related peptide for migraine prevention.

We found low to high quality of evidence to recommend eptinezumab, erenumab, fremanezumab, and galcanezumab in patients with episodic migraine and medium to high quality of evidence to recommend erenumab, fremanezumab, and galcane- zumab in patients with chronic migraine.

For several clinical questions, there was not enough evidence to provide recom- mendations using the GRADE approach and recommendations relied on experts’ opinion.

Monoclonal antibodies acting on the calcitonin gene-related peptide are new

drugs which can be recommended for migraine prevention.

Extended: The aim of this guideline is to provide evidence-based and expert- based guidance to clinicians for the management of episodic migraine (EM) and chronic migraine (CM) with CGRP mAbs.

Future biomarker research should identify patients more prone to respond to

CGRP mAbs and enable clinicians to personalize treatment decisions.

Introduction Some patients may treat their migraine attacks with drugs to relieve pain but in some patients because of frequency, severity and impact on quality of life, preven- tive treatment is required to reduce the occurrence of acute attacks and the need of medications to relieve the pain.

Many years have passed since the first mechanism-based drug, methysergide,

was introduced for migraine treatment [148].

Other drugs, including calcium-channel antagonists, antidepressants, antiepilep- tics, anti-hypertensives developed for indications other than migraine entered the field based on clinical studies [149–152].

Poor tolerability and side effects are important limitations of available preventive

treatments.

Those new treatments are migraine specific whereas all the other available pre- ventive drugs were developed for indications other than migraine and have an unclear mechanism of action considering migraine pathophysiology.

Methods We included (1) observational (prospective) and intervention studies in which an CGRP mAb was assessed as possible treatment strategy for migraine prevention; (2) studies published in English or in other languages if a reliable translation could be obtained; (3) reliable criteria to diagnose migraine; (4) treatment for migraine prevention with any form of CGRP mAb; (5) reporting any outcome referring to migraine frequency, severity, duration, disability, or use of drugs to treat the acute attacks before and after treatment or in treated and untreated patients.

4.2 Preventive Treatment

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We excluded studies (1) with observational designs not reporting outcomes with treatment or not comparing at least two treatment strategies; (2) performed in patients with headache other than migraine; (3) not reporting information on the outcomes selected for the PICO and clinical questions; (4) published only in the form of abstracts or presented at conferences only.

Quality of evidence was addressed for single studies and for selected outcomes

according to the GRADE approach [153].

Results A phase IIIb study, the LIBERTY trial, evaluated the efficacy of erenumab 140 mg monthly dose as compared to placebo in patients with EM who had been treated unsuccessfully (in terms of either efficacy or tolerability, or both) with between two and four preventive treatments [154].

A sub-analysis of patients using fremanezumab as an add-on treatment [155] and pooling together data of patients with EM and CM showed that among patients who received fremanezumab as add-on to their preventive treatment there was a signifi- cant decrease in the number of migraine days relative to placebo (−4.1 versus −2.5), an increase in the number of patients who had improvement by 50% or more of migraine days (40% versus 24%; P = 0.0505) and a reduction in the mean number of days using acute medications (33% vs 26%).

Conclusions CGRP mAbs appear promising drugs for migraine prevention.

Acknowledgement A machine generated summary based on the work of Sacco, Simona; Bendtsen, Lars; Ashina, Messoud; Reuter, Uwe; Terwindt, Gisela; Mitsikostas, Dimos- Dimitrios; Martelletti, Paolo. 2019 in The Journal of Headache and Pain.

Erenumab: First Global Approval