Precision migraine medicine may be guided by saliva CGRP levels


By Michael Woodhead

11 Aug 2022

A precision approach to migraine preventive therapies may be possible based on salivary CGRP levels, according to neurologists in Spain.

Their research has shown that a person’s baseline CGRP levels were able to predict their migraine frequency and also their responses to treatment with the CGRP inhibitor erenumab.

In a pilot study, they recruited 43 patients with episodic or chronic migraine from a hospital headache clinic and also a healthy control group of 27 age-matched people with no history of regular headache.

At baseline, all participants underwent saliva testing for CGRP levels, and then patients with migraine received erenumab 140 mg subcutaneously every four weeks.

The results, published in Annals of Neurology, showed that higher CGRP levels at baseline were significantly associated with a higher headache frequency (mean headache days) in patients with chronic or episodic migraine.

However, rates of depression were also associated with CGRP levels, and in patients with depression, the association between CGRP levels and headache was attenuated.

The researchers identified a cut-off point for salivary CGRP levels of 104 pg/mL to differentiate migraine from controls, with an area under ROC curve (AUC [95.0 CI]) of 0.801 [0.798–0.804].

When assessing treatment response after three doses of erenumab, they found that higher pre-treatment salivary CGRP levels were statistically significantly associated to a higher probability of having 50% or greater reduction in headache frequency in episodic migraine patients, but not in chronic migraine patients.

“In patients with higher headache frequency, the likelihood to response to CGRP-mAbs was dramatically reduced, suggesting that salivary CGRP levels are not associated to treatment response in chronic migraine patients,” they wrote.

They postulated that peripheral regulation of CGRP was not enough in these patients, and in chronic migraine with frequent headache there must be other biological or genetic mechanisms involved.

After 12 weeks of treatment with erenumab, they noted that salivary CGRP levels from patients within all spectrum of migraine frequency converged to similar CGRP values, except in patients with concomitant depressive symptoms.

The researchers said their findings suggested that there was a ‘molecular spectrum’ of CGRP levels “with a pathophysiological meaningful turning point of the disease, which is related to impact and treatment response”.

“On a practical clinical level, this supports, on one hand, the importance of treating migraine patients with effective preventive treatments earlier in the development of the disease since it seems that there is a possibility of reverting migraine molecularly before it reaches a no-return turning point with the current therapeutic option,” they said.

The link between headache and depression had been seen in previous studies and suggested shared genetic polymorphisms between migraine and depression, they added.

“Our study not only supports this linear relationship between headache frequency and depression but also states that CGRP could play an important role in this relation. Perhaps one could hypothesize in its neuroinflammatory central function, for which anti-CGRP monoclonal antibodies do not have as much access due to their very low permeability through the brain blood barrier,” they wrote.

They concluded that saliva offered a relatively easy and non-invasive way to measure CGRP levels, and it was worth exploring further a role for guiding migraine treatment decisions, particularly in patients with episodic migraine.

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