Headlines from the 2014 AHS Annual Meeting
The 56th annual scientific meeting for the American Headache Society occurred in Los Angeles, California on June 26-29, 2014. The theme for this year’s meeting was “Researching and Understanding Both Hemispheres of Migraine”. A great deal of exciting research was presented, including data on monoclonal antibodies and migraine prevention, the link between migraine and cardiovascular disease in women, infant colic and early migraine, and peripheral nerve blocks for headache.
There is a plethora of exciting data for the use of monoclonal antibodies that target the calcitonin gene-related peptide (CGRP) pathway for the prevention of migraines.1 While these potential treatments are still in the early stages of development, they could eventually be the first mechanism-based, migraine-specific therapy for migraine prevention. One of the agents being studied, ALD403, is a genetically engineered humanized CGRP antibody that is delivered intravenously. In a double-blind, placebo-controlled, randomized trial, a greater proportion of patients receiving ALD403 experienced a reduction in migraine days than those receiving placebo. Though not statistically significant, during weeks 9 to 12, 75.3% of ALD403-treated patients had a 50% reduction in migraine days versus 66.7% of placebo treated patients (P=0.1603). However, a significantly greater proportion of patients receiving ALD403 had a 75% reduction in migraine days versus placebo (53.4% vs 30.8%, P=0.0039); 41.1% patients receiving ALD403 vs 16.7%, who received placebo had a 100% reduction in migraine days (P=0.0008). A second, fully humanized monoclonal antibody to CGRP, LY2951742, also showed positive results in a double-blind, placebo controlled trial. In this study of subcutaneous LY2951742, there was a significantly greater change in mean headache days at 3 months for those receiving LY2951742 (-4.2 days) versus those receiving placebo (-3.0 days); P=0.003. Additionally, LY2951742 demonstrated superior results for all secondary endpoints, which included headache days, migraine attacks, and 50% responder rate. A third drug, AMG 334 that is under investigation binds to the CGRP receptor itself, and is currently in 2 Phase 2 randomized, double-blind, placebo-controlled, multicenter trials. The first trial is examining the safety and efficacy of AMG 334 in migraine prevention, and the second is evaluating the safety and efficacy of the drug in chronic migraine prevention. Data for this new class of treatment are exciting, and have the potential to change the way people with migraines are treated.
Another subject highlighted at the meeting was the link between migraine and cardiovascular disease in women.2 An ongoing prospective cohort study of female registered nurses in the US was initiated in 1989 and collected self-reported data every 2 years for incidence of cardiovascular disease (confirmed through medical record review by physicians). In the baseline questionnaire, and 2 subsequent questionnaires, women reported whether they had been diagnosed with migraine by a physician. Data for 115,541 women through June 2011 were analyzed. Overall, women who had been diagnosed with migraine had more unfavorable cardiovascular disease risk than those who did not have a diagnosis of migraine, including a history of hypertension, hypercholesterolemia, were currently smokers, used postmenopausal hormones, and had a family history of myocardial infarction (MI). In this study, those who reported migraine had a statistically significant multivariable adjusted risk of developing total cardiovascular disease (hazard ratio, 1.52; 95% confidence interval [CI], 1.36 – 1.71) versus with women without migraine. Additionally, it was found that women with migraine had a higher risk of developing secondary cardiovascular disease outcomes: MI: HR, 1.42 (95% CI, 1.20 – 1.68); stroke: HR, 1.65 (95% CI, 1.40 – 1.95); angina/revascularization: HR, 1.75 (95% CI, 1.30 – 2.34); and cardiovascular disease mortality: HR, 1.43 (95% CI, 1.06 – 1.93). Study limitations include self-reported diagnosis of migraine, possibly leading to misclassifications. This research does not include information about migraine aura status, as aura has been linked to an increased risk for stroke. Further studies may help to elucidate the relationship between risk for cardiovascular disease and migraine in women.
A meta-analysis of 3 studies (totaling 891 study participants) that examined the potential link between infant colic and early migraine was also presented.3 In a pooled random effects model, the odds ratio for the relationship between infantile colic and migraine was 5.6 (95% CI, 3.3-9.5; P=0.004), indicating a robust association between the two. The causes of infant colic are still not fully understood, and though some believe there is a relationship between colic and gastrointestinal distress, the data are questionable. Because infantile colic can be extremely stressful for parents, it is important to gain a better understanding of the underlying pathology of the condition. Further studies should be conducted to examine this relationship, as this may provide additional information for physicians and parents in the treatment of infants with colic.
Data from a multicenter study of patients receiving peripheral nerve blocks were also presented.4 A central electronic database was used to collect demographic and other information from adult patients who had been diagnosed with a headache disorder that was not controlled by other therapies at the time of receiving a nerve block. Patients reported if they had ever had previously received a nerve block, what medication they had used that day to treat their headache and what medications they were taking on a daily basis for prevention, the location of their headache, the severity, and how long it had lasted. Physicians provided data on the type of block performed, whether it was bilateral or unilateral, and the type and dose of medication used. Patients reported their pain levels immediately after the nerve block was performed, and then again in 2 weeks. The study reported data for 164 patients. The majority of patients (58.3%) had migraine; 50.6% of the 164 patients had a peripheral nerve block in the past and 66.7% were being treated for migraine prophylactically. The vast majority of patients who received a peripheral nerve block had nerve root tenderness at the injection site. Before the nerve block, 71.2% of patients rated their pain between a 4 and 8 out of 10, and after the nerve block, nearly half (47.2%) reported a reduction in pain level to 1 out of 10. For some patients (25%), pain relief only lasted for a matter of hours; 41.4% said it lasted for 2 weeks, and 30.3% said it lasted days. The majority of patients (74%) were either very satisfied or satisfied with the procedure. While the use of peripheral nerve block did help some patients, further studies on the their use are needed to gain a better understanding as to what patients may benefit the most from this type of migraine treatment.
Much research continues to be conducted in the area of migraine. Additional research that was presented at the annual AHS meeting can be found on the organization’s website.