Genetic Risk Score May Be Effective for Predicting Migraine Response to Triptans

Previous studies have identified many risk loci for migraine without aura (MwoA)—the most common form of migraine. Recently, researchers tested the hypothesis that a genetic risk score based on single-nucleotide polymorphisms (SNPs) may influence headache response to triptans in patients and found a significant relationship between triptan efficacy and the cumulative score of genetic risk.

The study involved a cohort of triptan-treated patients with MwoA. The researchers evaluated the predictive role of 6 single-locus markers (rs9349379, rs2078371, rs6478241, rs11172113, rs1024905, and rs6724624) that were recently identified at the genome-wide level of significance as risk factors for MwoA.

“MwoA, the most common form of migraine, is typically characterized by attacks of throbbing and unilateral headache pain lasting from 4 to 72 hours, usually accompanied by nausea, vomiting, photophobia, and phonophobia,” noted the authors. “The acute treatment of migraine includes selective 5HT1B/D receptors agonists, collectively known as triptans, which are currently recommended as the first-line therapy for moderate to severe migraine attacks. Despite the well-established efficacy and safety of triptans, about one-third of migraineurs treated with them do not adequately respond, even after a switch to a different triptan.”

Patients recorded their migraine pain intensity before taking the treatment and then again 120 minutes later using a 4-point pain scale. Based on the information, they were then stratified as either consistent responders—those with at least a 2-point decrease in pain level—or inconsistent responders.

Among the 172 patients, 36.6% had inconsistent responses to triptans. Patients using triptans other than frovatriptan (52.3%) tended to have a lower risk of inconsistent response than those using frovatriptan. Sex, age, and use of prophylactic medications were similar between the 2 groups. While the logistic regression analysis showed detected a nominal association between rs6724624 and inconsistent response (OR, 2.14; 95% CI, 1.19-3.89), the association did not remain after being corrected for multiple comparisons.

To assess the cumulative effects of SNPs on individual risk of poor response to triptans, the researchers created 5 genetic risk scores by adding the number of risk alleles for MwoA at different selected loci. While there were no significant differences in mean scores for the top 6, 5, 4, and 3 top-ranking variants, GRS-2, which was constructed with risk alleles of the 2 top-ranking SNPs (rs6724624C and rs1024906G), was inversely associated with the risk of inconsistent response.

The researchers noted that the association remained significant even after correction for multiple testing.

They suggest that their findings must be confirmed in large prospective studies; however, these results reinforce the idea that genetic risk score may be a useful tool for evaluating the impact of genetic constitution on headache response.

Reference:

Cargnin S, Viana M, Sances G, et al. Using a genetic risk score approach to predict headache response to triptans in migraine without aura [published online September 26, 2018]. J Clin Pharmacol. doi: 10.1002/jcph.1320.