Migraine studies find new drug, several existing options all effective for acute treatment
An industry-funded trial found that migraine pain resolved sooner with eptinezumab than placebo, while a meta-analysis found that several established and newer therapies for the acute treatment of migraine were associated with reductions in short-term pain.
Two recent studies—an industry-funded trial and a meta-analysis—focused on acute migraine treatment.
The trial looked at eptinezumab, an anti-calcitonin gene-related peptide antibody that received FDA approval for migraine prevention in February 2020, as an acute migraine treatment. The phase 3 trial was conducted from November 2019 to July 2020 at 47 sites in the United States and the country of Georgia. Adults with at least a one-year history of migraine, with four to 15 migraine days per month in the three previous months, were randomized to either IV eptinezumab, 100 mg (n=238), or placebo (n=242), administered within one to six hours of onset of a moderate to severe migraine attack. The study was sponsored and funded by the drug's manufacturer, H. Lundbeck A/S, including editorial support for the study manuscript. Results were published June 15 by JAMA.
Patients given eptinezumab had statistically shorter times to headache pain freedom (median, four hours vs. nine hours; hazard ratio [HR], 1.54; P<0.001) and to absence of their most bothersome symptom (median, two hours vs. three hours; HR, 1.75; P<0.001). At two hours after infusion, 23.5% versus 12.0% were free of headache pain (odds ratio [OR], 2.27; 95% CI, 1.39 to 3.72; P<0.001) and 55.5% and 35.8% had absence of their most bothersome symptom (OR, 2.25; 95% CI, 1.55 to 3.25; P<0.001). Fewer eptinezumab-treated patients (31.5% vs. 59.9%) used rescue medication within 24 hours (OR, 0.31; 95% CI, 0.21 to 0.45; P<0.001).
Also, a systematic review and meta-analysis, sponsored by the Agency for Healthcare Research and Quality and also published June 15 by JAMA, looked at established and newer therapies for the acute treatment of migraine. The analysis of 15 systematic reviews and 115 randomized clinical trials including 28,803 participants with migraines found that multiple acute interventions were associated with improvements in short-term pain outcomes compared to placebo, including NSAIDs, triptans, calcitonin gene-related peptide receptor antagonists, 5-HT1F receptor agonists, dihydroergotamine, acetaminophen, and remote electrical neuromodulation. While these treatments had moderate to high strength of evidence (SOE), opioids had low or insufficient evidence to support their use, the review found.
Triptans and NSAIDs used individually were significantly associated with reduced pain at two hours and one day (moderate to high SOE) and increased risk of mild and transient adverse events. Calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and mild adverse events.
Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant differences in adverse events was noted between nonpharmacologic and sham treatments.
An editorial accompanying both papers stated that while the systematic review provides a better understanding of currently available acute treatments, the study of eptinezumab shows that new classes of treatments are blurring the line between acute and preventive migraine therapies. Taken together, the reports communicate an optimistic message, the editorial stated. However, clinicians need comparative effectiveness and safety studies among different acute treatments for migraine, including devices.
“Unrelenting and bold research is required to continue development of new acute therapies,” the editorial stated. “Effective, reliable, and safe acute treatment for migraine is within reach, and patients deserve nothing less.”