Feb 29

The right drug for the right patient - how QST can point to who will benefit from Migraine medication

In this blog, we will explore the use of Quantitative Sensory Testing (QST) as a tool to help identify whether a drug might be a suitable treatment for an individual migraine sufferer.

QST is used in pain clinics to determine pain classification, as well as determine a right fit for specific drugs. (Bruneau, 2022) (Yarnitsky, 2012)

Migraines - what are they?

According to Mayo Clinic, migraine is a genetic neurologic disorder that affects individual sufferers in a range of severity and duration. Some sufferers will have a migraine attack on rare occasions, while others may have a migraine many days in a month. The duration of the migraine attack also varies from person to person, lasting at least 4 hours, while for some, migraine can last for up to 72 hours. To make matters even more dire, since migraines are genetic, if one parent suffers from migraines, there is a 50% probability that their child will also carry that burden.

The difference between Episodic and Chronic Migraines

Migraines come in more than one form. Cleveland Clinic provides a detailed description of both Chronic and Episodic migraines. While both may have the same symptoms, chronic migraines (CM) happen more often or last for a longer duration. Migraines are considered chronic when the sufferer experiences headaches on at least 15 days each month and when those headaches include migraine symptoms like pulsating one-sided headache, inability to tolerate light and sound, nausea or vomiting for at least 8 days per month; occurring for a period of 3 months or longer.

Migraines and sensory processing

Recently there is increasing evidence that migraine sufferers have irregularities in processing sensory information originating from the visual, auditory, olfactory, and somatosensory organs. Additionally, abnormalities in pain perception, e.g. Allodynia – pain in response to a non-painful stimulus, are caused by the increased nerve responsivity of the trigeminovascular neurons feeding into the somatosensory cortices (Ashina, 2023).

Phenotyping and Quantitative Sensory Testing

Amidst progress in pain research and the expanding landscape of pharmaceutical treatments, it becomes crucial to accurately phenotype the patient to better a better suited drug. Instead of relying on trial-and-error approaches, incorporating phenotyping tools such as Quantitative Sensory Testing (QST) is imperative. These tools play a pivotal role in enhancing the precision of the decision-making process regarding the most suitable pharmaceutical interventions for individual patients. (Edwards, 2021) As you read on, you will see how QST has had an almost magical, crystal ball effect in the realm of migraine medications.

Preventive Migraine treatment with CGRP-mAb

In their research on high-frequency episodic migraine and chronic migraine Ashina et al. chose to look at prophylactic migraine treatment with galcanezumab, a monoclonal antibody against calcitonin gene-related peptide (CGRP-mAb). The researchers in this case explored the connection between cephalic allodynia experienced in the non-ictal phase and the efficacy of galcanezumab as a preventive treatment for migraine.

This study used 3 types of stimuli to test pain thresholds: heat, cold and mechanical. Thermal thresholds were assessed using Medoc’s Q-Sense with the Method of Limits. Mechanical thresholds were assessed using Von Frey monofilaments. The strictest criteria for allodynia were used: heat pain thresholds below 40ºC, cold pain thresholds above 20ºC, mechanical pain thresholds <60 g Von Frey monofilament. Inclusion in this prospective, observational, open-label cohort study was based on migraine diagnosis by a neurologist and headache specialist, according to the 3rd edition of the International Headache Classification of the International Headache Society (ICHD-3), suffering from migraines 8 or more days per month for the past 3 months. Participants in the study were required to refrain from beginning or changing their prophylactic medication routine for medications other than those for migraines (medications such as antidepressants, antiepileptics, etc.) so as not to risk interference with the study results. (Ashina, 2023)

Predicting who will benefit from Galcanezumab

In this study, responders were those who showed >50% decrease in average monthly migraine days during the three treatment months compared to percentage of pre-treatment migraine days in the pre-treatment month. The researchers found that allodynia at the supra-orbital site could predict galcanezumab responders with nearly 80% accuracy and identify galcanezumab non-responders with nearly 85% accuracy. These promising conclusions, based on the resulting 21% incidence of pre-treatment non-ictal cephalic allodynia in 24 responders and the 85% incidence of allodynia in the 19 non-responders. Incidentally, there was no statistically significant difference in incidence of allodynia between the high-frequency episodic migraine and the chronic migraine group, nor in responders’ ratio between these two groups of patients. (Ashina, 2023)

Flunarizine for Chronic Migraine

In another prospective open-label study by Pan et al, using Medoc’s TSA-II, QST was performed to assess the relation between QST measures and treatment efficacy in preventive treatment-naïve CM sufferers receiving flunarizine. Flunarizine is the most prescribed prophylactic in Taiwan and recommended as a first-line prophylactic by the European Federation of Neurologic Societies. Additionally, differences in pain sensitivity between a group of 50 healthy controls and 84 CM patients were assessed using QST. CM diagnosis was based on ICHD-3.

Thermal testing was conducted according to the DFNS (German Research Network for Neuropathic Pain) standards using the Method of Limits. The heat pain threshold (HPT) and cold pain threshold (CPT) were tested using the standard 30mm x 30mm thermode.

Following flunarizine treatment, 24 (29%) CM patients were considered responders with ≥50% reduction in the number of monthly headache days throughout the 12-week treatment period.

Flunarizine efficacy and QST

The decision tree analysis, as it appears in Pan et al, gives a good perspective of the accuracy of the QST testing and the difference between CM responders and non-responders. Those more likely to be responders were patients with HPT >44.9ºC (p=0.002) or mechanical pain thresholds (MPT) >158 g (p=0.020) measured with Von Frey monofilaments over the V1 dermatome (ophthalmic branch of the trigeminal nerve). Furthermore, overall accuracy for having a treatment response was 80%, and the sensitivity, specificity, positive, and negative values were 87%, 63%, 85%, and 65%, respectively. The results of this study were also conclusive, showing compared to patients with relatively normal pain sensitivity, chronic migraine patients with lower V1 MPT or V1 HPTs were less responsive to the flunarizine treatment. To conclude, cutoff values for the identification of flunarizine prophylactic treatment responders are >44.9 C HPT or >158 g MPT measured over the V1 dermatome. (Pan, 2022)

Worldwide, migraine is one of the most prevalent diseases, ranking the 6th highest cause of disability. Given the numbers – and we did not even get into the socio-economic effects of migraine on the patient, which were estimated in a European study to be a mean of one workday, one to two housework days, as well as missed social events. In the U.S., the numbers are even higher, and it is estimated that migraines are the cause of >50% reduction in productivity (Agosti, 2018) Clearly, finding the ‘right drug’ for each patient is of paramount importance, not only from a pain perspective, but also to reduce the socioeconomic disability burden of missed workdays in addition to the cost of the drug treatment and additional doctor visits, etc.

How QST can give important answers to clinicians treating Migraine sufferers

In high-frequency and chronic migraine patients specifically, where the disease burden due to the number of headache days per month is this high, the call for finding the right preventive treatment becomes critical. These studies have clearly demonstrated that the use of Quantitative Sensory Testing has a clear and consistent value in determining whether a particular preventive migraine drug would be effective for specific patients. Given the amount of migraine drugs on the market, the ability to assess the potential personal effectiveness of a drug is a terrific benefit, especially considering the alternative ‘trial and error method’ requiring the patient try one drug after another until reaching ‘the one’ that works for them.

QST, a simple, non-invasive, and mostly non-painful test that can be performed in the clinic, ensuring a more accurate determination of what medication is the best solution for each migraine patient, saving the patient from additional pain, time, as well as lessening the economic and socio-economic disability burden.