This transcript has been edited for clarity.
Dear colleagues, I’m Hans-Christoph Diener from the Faculty of Medicine at the University of Duisburg-Essen in Germany.
CGRP receptor agonists
Let me start with the treatment of acute migraine attacks. Until recently, we had analgesics, nonsteroidal anti-inflammatory drugs like ibuprofen, ergot alkaloids, and triptans. There are new developments, which are small molecules that are antagonists at the calcitonin gene-related peptide (CGRP) receptor. At the moment, we have three of them: rimegepant 75 mg, ubrogepant 50 mg or 100 mg, and zavegepant (a nasal spray) 10 mg.
These are all effective and superior to placebo. The 2-hour pain-free rate is somewhere between 25% and 30%. They have very few side effects; these include a little bit of nausea, somnolence, nasopharyngitis, and for zavegepant, the nasal spray, taste disturbance. In indirect comparisons, the so-called gepants are about as effective as ibuprofen and aspirin, and they seem to be less effective than sumatriptan 100 mg.
Unfortunately, until now, we have no direct comparison with triptans and we have no data demonstrating whether they are effective in people where triptans do not work. The major shortcoming is the cost in the United States. The cost per tablet or nasal spray is somewhere between $80 and $200. This means we definitely need more studies for these gepants.
Migraine prophylaxis
Let me move to the prophylaxis of migraine with drugs. Previously and still, we have all medications like beta-blockers, flunarizine, topiramate, valproic acid, amitriptyline, and candesartan, and for chronic migraine, onabotulinumtoxinA. We have now 5 years’ experience with the monoclonal antibodies against CGRP or the CGRP receptor like eptinezumab, erenumab, fremanezumab, and galcanezumab.
These are all equally effective. They reduce migraine-days between 3 and 7 per month. They are effective both in episodic and chronic migraine, and most importantly, they are effective in people with medication overuse headaches. The 50% responder rates are somewhere between 40% and 60%, and there are no significant differences between the four monoclonal antibodies.
The major advantage is a very good tolerability profile; very few patients terminate treatment because of adverse events. There has been, with one exception, no direct comparison of the monoclonal antibodies with traditional migraine preventive drugs or onabotulinumtoxinA. The only exception is a trial that compared topiramate and erenumab, showing that erenumab was definitely more effective and better tolerated.
At the moment, the recommendation is to use these monoclonal antibodies for 12 months in episodic migraine and 24 months in chronic migraine and then pause. It usually turns out that between 50% and 70% of these patients need to continue the treatment. If they are not working, there is a possibility to switch between the monoclonal antibodies, and the success rate after this is somewhere between 15% and 30%.
Gepants were also developed for the prevention of migraine. Here, we have rimegepant 75 mg every other day or atogepant 60 mg daily. They are effective, but in indirect comparisons, they are less effective than the monoclonal antibodies. At present, we have no comparative trials with monoclonal antibodies or the traditional migraine preventive drugs.
Potential patients are those who have needle phobia or patients who do not respond to monoclonal antibodies. Again, the biggest shortcoming is cost in the United States. The cost per year for migraine prevention or prophylaxis is between $12,000 and $20,000.
Finally, we also had very exciting news. There is a new therapeutic approach via PACAP. PACAP is pituitary adenylate cyclase-activating polypeptide, which has similar biological actions as CGRP but with additional actions. It could very well be that people who do not respond to a monoclonal antibody would respond to a monoclonal antibody against PACAP.
At the congress, the first randomized, placebo-controlled trial with a monoclonal antibody against PACAP was presented. This monoclonal antibody was effective in a population of people in whom prior preventive therapy had failed. A phase 3 study is planned, and most probably the PACAP monoclonal could work in people who do not respond to monoclonal antibodies against CGRP.
Dear colleagues, we have now many choices for the acute treatment of migraine and migraine prophylaxis. We have new kids on the block, and we have to learn more about how to use these drugs, their benefits, and their shortcomings.
He has disclosed the following relevant financial relationships:Received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Abbott; Addex Pharma; Alder; Allergan; Almirall; Amgen; Autonomic Technology; AstraZeneca; Bayer Vital; Berlin Chemie; Bristol-Myers Squibb; Boehringer Ingelheim; Chordate; CoAxia; Corimmun; Covidien; Coherex; CoLucid; Daiichi-Sankyo; D-Pharm; Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 3M Medica; MSD; Medtronic; Menarini; MindFrame; Minster; Neuroscore; Neurobiological Technologies; Novartis; Novo Nordisk; Johnson & Johnson; Knoll; Paion; Parke-Davis; Pierre Fabre; Pfizer; Schaper and Brummer; Sanofi-Aventis; Schering-Plough; Servier; Solvay; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.
Dr. Diener is professor, department of neurology, Stroke Center-Headache Center, University Duisburg-Essen (Germany).
A version of this article appeared on Medscape.com.