Effects of Intravenous Eptinezumab vs Placebo on Headache Pain and Most Bothersome Symptom When Initiated During a Migraine Attack. A Randomized Clinical Trial
RCT (n=480) found significantly faster freedom from headache pain (median, 4 hours vs 9 hours;P < .001) and absence of most bothersome symptom (median, 2 hours vs 3 hours; P < .001) with eptinezumab vs placebo, respectively. Results remained significant at 4 hours after infusion.
Source:
Journal of the American Medical Association
SPS commentary:
A related editorial discusses this trial. It notes that this is the first study to report rapid, acute benefits of a CGRP monoclonal antibody started for prevention, thereby serving as a possible inflection point for how clinicians conceptualise the role of CGRP monoclonal antibodies as migraine therapies. Another recent clinical trial demonstrated the preventive effectiveness of rimegepant, a small-molecule CGRP receptor antagonist FDA approved for the acute treatment of migraine. Both of these studies evaluated treatments targeted at CGRP or its receptor and indicate that this class of therapies may transcend the traditional dividing line between acute and preventive migraine medications. The possibility of an entirely new approach to migraine treatment, whereby acute therapies may have preventive benefit and preventive treatments have immediate effects, is an intriguing step forward for the field.
A systematic review for acute treatments for migraine is also reported in this edition of JAMA. It found triptans, NSAIDs, paracetamol, dihydroergotamine, CGRP antagonists, lasmiditan, and remote electrical neuromodulation, showed improvements in short-term pain. There was limited evidence for use of opioids. The editorial notes it is the first systematic review to include the newer gepant and ditan medication classes and to use the same methodology to evaluate both devices and medications. A clear message from this review is that opioid medications are not an appropriate acute treatment for migraine. Based on 13 clinical trials, opioids were judged to have low strength of evidence for the acute treatment of migraine. None of the clinical trials that evaluated opioid use for acute migraine treatment measured risks such as opioid overdose or misuse, development of medication overuse headache, or conversion to chronic migraine as adverse events, but these complications have been well-described in other studies. Given the evidence-based effectiveness of many other medication classes, the lack of good evidence for effectiveness of opioids as acute treatment for migraine, and over whelming evidence of harm with frequent opioid use, it is clear that opioids should be used sparingly, if at all, for treatment of migraine.
The editorial concludes that choice of acute treatment should include considerations of effectiveness, adverse event profiles, safety concerns and contraindications, and cost. Triptans are the typical first-line treatment based on good-quality evidence for both effectiveness and safety. In patients whose migraines do not respond to triptans or who are unable to tolerate them, a trial of NSAIDs or gepants may be appropriate.