Head-to-head relief: ubrogepant, rimegepant, and zavegepant in migraine treatment

Migraine, a significant cause of disability worldwide, heavily impacts daily functioning and quality of life. Despite various acute treatment options, including nonsteroidal anti-inflammatory drugs (NSAIDs) and triptans, patients experience limited relief or adverse effects. This review examines the efficacy and safety of gepants - ubrogepant, rimegepant, and zavegepant - in the acute treatment of migraine. We assessed phase II and III clinical trials, focusing on clinically relevant endpoints such as pain freedom and freedom from the most bothersome symptom at two hours post-treatment. We calculated the number needed to treat (NNT) to achieve significant endpoints for each gepant. Gepants are recommended for the acute treatment of migraine in individuals who do not respond to triptan monotherapy or combination therapy, who experience only partial effectiveness, or who cannot tolerate or have contraindications to triptans. The NNT values for achieving pain freedom at two hours were 9 for rimegepant, 11 for zavegepant, and 12 for ubrogepant, which are comparable to NSAIDs such as naproxen (NNT = 11). Paracetamol, although not an NSAID, showed similar efficacy (NNT = 12). Triptans demonstrated lower NNTs, indicating higher efficacy. Gepants offer effective, well-tolerated alternatives with no significant cardiovascular risk and minimal potential for medication-overuse headache.