Precision medicine for migraine

Diversity and response to antimigraine medication

As Professor Antoinette Maassen van den Brink, Rotterdam, Netherlands explained, despite numerous clinical trials and some real-world evidence (RWE), knowledge of the pharmacology and related clinical effects of new treatments is low. Clinical trial data collected from mainly Caucasian, overweight females are not necessarily generalizable to all populations.¹ However, gender, body-mass index, age, ethnic background, ultrarapid metabolism, and other characteristics may affect the pharmacokinetics of therapies and contribute to low efficacy. Collection of RWE will expand knowledge on the effectiveness and safety of new migraine medications in a wider population.

Can we predict CGRP mAb super responders?

Uncovering differences between responders and non-responders to migraine medications will also help to improve migraine care. Defining patients who will derive greatest benefit from treatment with anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) may avoid unnecessary economic costs and adverse effects, said Dr Ana Rita Pinheiro, Lisbon, Portugal. Some response predictors have already been identified, which include:^2,3

Uncovering differences between responders and non-responders to migraine medications will help to improve migraine care

• Unilateral pain
• Allodynia in episodic migraine
• Response to triptans
• Lower number of failed preventives
• Lower frequency at baseline
• Shorter disease duration
• Lower analgesic intake.

Dr Pinheiro presented results of a sub-analysis of a prospective study conducted in her clinic to determine predictors of super response to preventive therapies. Super responders were defined as those with ≥75% reduction in migraine frequency for at least 6 months (n=29) and compared with super non responders (<25% frequency reduction; n=13).

Factors predictive of super response to CGRP mAbs were found to be lower baseline frequency of migraine attacks, episodic migraine, and response to triptans. Conversely, disease duration, aura, absence of medication overuse and absence of psychiatric comorbidities were not found to be predictors of super response.

Predictors of super response to CGRP mAbs include lower baseline frequency of migraine, episodic migraine, and response to triptans

Scientific rationale

The overlap between response to triptans and anti-CGRP mAbs may be explained by convergence in their mechanisms of action. During a migraine attack, activation of the trigeminovascular system leads to CGRP release, vasodilation of the intracranial arteries, sensitization and activation of pain and inflammation. mAbs targeting CGRP lead to modulation of pain transmission and reduction in sensitization either by removing excess CGRP or by blocking receptor binding. Triptans constrict extracerebral blood vessels and reduce trigeminal sensory nerve activation, inhibiting vasoactive peptide release (including substance P and CGRP) thus indirectly affecting the CGRP pathway.⁴

Future directions

Management decisions based upon patient characteristics could have a more prominent role in future migraine treatment

Anti-CGRP mAbs are increasingly used as migraine preventives due to their proven benefits in clinical and real-life studies. As knowledge increases about the use of CGRP-targeted therapies from RWE, management decisions based upon patient characteristics could have a more prominent role in the treatment of migraine, concluded Professor Maassen van den Brink.