Ten open questions in migraine prophylaxis with monoclonal antibodies blocking the calcitonin-gene related peptide pathway: a narrative review

J Headache Pain. 2023 Aug 1;24(1):99. doi: 10.1186/s10194-023-01637-7.

Abstract

The monoclonal antibodies (mAbs) blocking the calcitonin-gene related peptide (CGRP) pathway, collectively called here "anti-CGRP/rec mAbs", have dramatically improved preventive migraine treatment. Although their efficacy and tolerability were proven in a number of randomized controlled trials (RCTs) and, maybe even more convincingly, in real world settings, a number of open questions remain. In this narrative review, we will analyze published data allowing insight in some of the uncertainties related to the use of anti-CGRP/rec mAbs in clinical practice: their differential efficacy in migraine subtypes, outcome predictors, switching between molecules, use in children and adolescents, long-term treatment adherence and persistence, effect persistence after discontinuation, combined treatment with botulinum toxin or gepants, added-value and cost effectiveness, effectiveness in other headache types, and potential contraindications based on known physiological effects of CGRP. While recent studies have already provided hints for some of these questions, many of them will not find reliable and definitive answers before larger studies, registries or dedicated RCTs are available.

Keywords: CGRP; Clinical practice; Contraindications; Migraine; Monoclonal antibodies; Physiological effects.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Calcitonin
  • Calcitonin Gene-Related Peptide* / metabolism
  • Child
  • Humans
  • Migraine Disorders* / drug therapy
  • Migraine Disorders* / metabolism
  • Migraine Disorders* / prevention & control
  • Receptors, Calcitonin Gene-Related Peptide / metabolism

Substances

  • Calcitonin Gene-Related Peptide
  • Antibodies, Monoclonal
  • Calcitonin
  • Receptors, Calcitonin Gene-Related Peptide