What is the “Best” Migraine Therapy? Old vs New, New vs New
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While 2021 was replete with a variety of woes that any sane person would prefer to see recede and vanish in the rearview mirror, amidst the gloom induced by the endless pandemic the arsenal of effective therapies for migraine continued to blossom and grow.
Since May 2018 there have emerged no less than nine new therapies for migraine: three subcutaneously self-injected anti-CGRP monoclonal antibodies (Mabs), one intravenously infused anti-CGRP Mab, three oral anti-CGRP “gepants”, a novel oral serotonin agonist (a “ditan”) which is active at a different site than the triptans in the migraine circuitry and an old drug (dihydroergotamine/DHE) available in an interesting new delivery system. That’s a lot of newcomers within a short period of time.
Dampening the enthusiasm for these newcomers has been the necessity for patients typically to obtain prior authorization (PA) from their insurers before trying them and thus for providers to spend financially uncompensated time and effort assisting with the PA and appeals process. Often there are hurdles placed by the insurer before authorization will be granted. For example, one may need to try and fail three generic and relatively inexpensive oral prevention therapies before receiving a chance to try an anti-CGRP Mab. Another example: insurers may require that a client/patient try and fail three oral triptans before authorization is granted for one of the new acute migraine treatments.
These last requirements raise an interesting couple of questions:
Just how well do the newcomers compare to the older therapies for migraine in terms of safety, tolerability and effectiveness?
For that matter, how do the newcomers compare to one another?
Well, the honest answers to both questions is…hard to say. With the exception of the triptans, the older therapies were developed for other medical indications and found serendipitously to be useful for treating migraine as well. The medications listed earlier - the CGRP Mabs and the rest – are “designer drugs” which were developed specifically for migraine. Does that make them better? Hmmm. Generally speaking, the mechanism by which they work to reduce migraine has been more clearly identified than is the case with the older therapies, and more to the point clinically they tend to have fewer side effects than the “oldies”, but few “active comparator” studies evaluating a given older drug against a given newcomer have been performed. As such, not much is known regarding the effectiveness of “old” versus “new”.
There are a few tidbits.
Botox (FDA approved for chronic migraine in 2010 and thus not strictly a “newcomer”) was directly compared to topiramate in the FORWARD chronic migraine study, and because of significant differences in tolerability favoring Botox it appears to be the more useful therapy.
For patients receiving Botox who have experience a partial positive response to injection therapy with the neurotoxin, the addition of erenumab (Aimovig) appears to further reduce migraine burden.
When compared to topiramate, Aimovig is more effective for migraine prevention and far better tolerated.
Switching from one anti-CGRP Mab to another appears to improve treatment response in some patients…although it still remains unknown whether one Mab is superior to the other three.
And that’s about it. Providers complain when insurers require that a patient with chronic migraine try and fail a beta blocker before authorization to receive Botox or an anti-CGRP therapy will be provided. How does “old” propranolol, a beta blocker, compare with Botox or an anti-CGRP medication in treating chronic migraine? No one can say with certainty, but one recent study did demonstrate propranolol can reduce headache burden in chronic migraine, and such data make it difficult to criticize insurers for requiring a trial of (inexpensive) propranolol prior to authorization of (much more expensive) anti-CGRP Mabs.
For better or worse, in welcoming the newcomers we will not be abandoning the older therapies. For now it’s best to think of these newcomers as attractive alternatives when the older therapies are ineffective, poorly tolerated or both.
