Patient selection for migraine preventive treatment with anti-CGRP(r) monoclonal antibodies

ABSTRACT

Introduction: Migraine is the most common neurological disorder and represents the first cause of disability in under 50s in both genders. Available preventive drugs were primarily developed for indications other than migraine and with an unclear mechanism of action in migraine pathophysiology.

Areas covered: This article reviews current preventive treatments and their shortcomings and the road that, through the understanding of calcitonin gene-related peptide (CGRP) role in migraine pathophysiology, carried to the approval of the 3 first-in-class monoclonal antibodies (mAbs) acting on the CGRP pathway. Data from phase 2 and phase 3 clinical trials of erenumab, galcanezumab and fremanezumab, both for episodic and chronic migraine prevention, are consistent for safety and efficacy.

Expert opinion: Anti-calcitonin gene-related peptide mAbs have potential advantages over conventional treatments such as ease of use, quick onset of action, persistent efficacy, placebo-like safety profile and absence of pharmacological interactions. Pharmacoeconomic studies should evaluate the economic impact of these drugs taking into account the overall direct and indirect costs related to untreated migraine and to migraine treated with the other available preventive therapies. Given the high cost of these therapies, it is essential to implement all possible strategies to optimize their effectiveness by optimization of patients’ selection.

KEYWORDS:

• Migraine
• chronic migraine
• treatment
• preventive
• anti-CGRP mAbs

Article highlights

• The Global Burden of Diseases 2016 reported that 1.04 billion people have a diagnosis of migraine, which is the first cause of disability in under 50s in both genders.

• Currently available preventive drugs were primarily developed for indications other than migraine and with an unclear mechanism of action in migraine pathophysiology.

• Inconstant efficacy, side effects, contraindications and pharmacological interactions are common shortcomings of all oral preventive treatments.

• CGRP has the role of playmaker in migraine pathophysiology and it represents the most evaluated target for currently in-development migraine treatments.

• Last year brought the approval of the 3 first-in-class monoclonal antibodies (mAbs) acting on the CGRP pathway (erenumab, fremanezumab and galcanezumab), and another (eptinezumab) is expected to enter the market by mid-2019.

• Data from phase 2 and phase 3 RCTs of erenumab, galcanezumab and fremanezumab, both for EM and CM prevention, are consistent for safety and efficacy.

Given the high cost of these therapies, it is essential to implement all possible strategies to optimize their effectiveness.

Declaration of interest

A Negro received travel grants, consulting fees and speaking fees from Allergan, Eli Lilly, Novartis, and TEVA. P Martelletti received travel grants, consulting fees and speaking fees from Allergan, Amgen, Eli Lilly, Novartis, and TEVA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

A reviewer of this manuscript has received honoraria from Supernus Pharmaceutical Inc. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.