Guideline recommendations from the International Headache Society (IHS) and the American College of Physicians (ACP) differ on optimal acute and preventive treatment strategies for migraine, according to a Grand Rounds discussion published in Annals of Internal Medicine.
Experts examined management approaches for a 27-year-old patient with migraine headaches occurring 2 to 15 days per month despite prior treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, gepants, and multiple preventive therapies.
Acute Treatment: Triptans vs Gepants
Guideline-supported acute therapies include NSAIDs, triptans, and gepants, although recommendations differ between organizations. The IHS recommends oral triptans as first-line therapy, whereas the ACP recommends a triptan combined with an NSAID or acetaminophen.
In systematic reviews informing IHS recommendations, ibuprofen 400 mg and naproxen 500 mg were associated with approximately 2.7 and 1.9 times the odds of pain freedom at 2 hours compared with placebo, respectively.
Triptans demonstrated higher efficacy in placebo-controlled analyses, although comparative trials often showed similar effectiveness to NSAIDs. Sumatriptan 50 mg and 100 mg were associated with approximately 2.6 and 3.2 times the odds of pain freedom at 2 hours.
Gepants showed lower relative effectiveness for this endpoint. Rimegepant 75 mg and ubrogepant 100 mg were associated with approximately 1.7 and 2.0 times the odds of pain freedom at 2 hours.
In a network meta-analysis of 137 trials, eletriptan was more effective than other triptans, NSAIDs, and gepants, with approximately 5 times the odds of pain freedom at 2 hours compared with placebo.
Triptans are contraindicated in patients with cardiovascular disease, and frequent use of most acute therapies—except gepants—can lead to medication overuse headache. Gepants are not associated with medication overuse headache and may be particularly useful in patients who do not respond to or cannot tolerate triptans or who are at risk for medication overuse headache.
Preventive Therapy: Limited Comparative Evidence
The IHS guideline identified 26 trials comparing preventive medications, none of which had high-quality evidence. Most showed no difference in efficacy between treatments.
Effectiveness is typically defined as a reduction in monthly migraine days of at least 50% for episodic migraine and 30% for chronic migraine.
Choice of preventive therapy depends on patient-specific factors, including reproductive considerations, adverse-effect profiles, cardiovascular risk, age, and prior treatment response.
CGRP-Targeting Therapies: Faster Response, Higher Cost
Calcitonin gene-related peptide (CGRP)-targeting monoclonal antibodies and oral antagonists are used for migraine prevention and may have a faster onset than traditional oral therapies. Many patients report improvement within 4 weeks compared with 3 to 4 months for oral preventive medications.
In the APPRAISE randomized trial of 621 patients with prior preventive treatment failure, erenumab led to a 50% or greater reduction in monthly migraine days in 56% of patients compared with 17% among those receiving oral preventive medications.
Treatment discontinuation due to adverse effects occurred in 23% of patients receiving oral preventive medications compared with 3% receiving erenumab.
However, the trial included only patients who had not responded to at least one prior oral preventive therapy, introducing potential selection bias.
Guideline recommendations differ regarding use of these therapies. The IHS does not specify a required sequence for CGRP-targeting therapies, whereas the ACP recommends reserving them for patients who have not benefited from oral preventive medications, citing cost and limited long-term safety data.
Annual costs for monoclonal antibodies range from approximately $7,000 to $23,000 compared with about $123 for metoprolol and $274 for valproate.
Management Strategies
In the presented case, one expert recommended a trial of aspirin, acetaminophen, and caffeine, continuation of ibuprofen and ubrogepant for acute treatment, and initiation of topiramate for prevention.
Another expert recommended continuing ubrogepant for acute management and initiating erenumab for prevention.
Both emphasized addressing modifiable risk factors, including medication overuse, sleep-related factors, and exposure to migraine triggers.
“Treatment should be patient-centered and informed by clinical variables such as headache pattern, comorbid conditions, reproductive goals, and avoidance of polypharmacy,” one expert noted.
Limitations
Most randomized studies of preventive migraine therapies are placebo-controlled, and comparative evidence remains limited.
In addition, the APPRAISE trial population included only patients with prior treatment failure, which may limit generalizability.
Disclosure forms are provided with the article online.
Source: Annals of Internal Medicine
