Update: How goes it with the anti-CGRP MABs?


Nine months have passed since the first of the anti-CGRP monoclonal antibodies (MABs), erenumab (Aimovig), became available for general clinical use. Shortly thereafter, two more MABs joined erenumab in the arsenal of therapies intended for migraine prevention, galcanezumab (Emgality) and fremanezumab (Ajovy).

All three MABs are FDA approved for migraine prevention, and in large-scale clinical trials all three were demonstrated to be safe, well-tolerated and more effective than placebo for reducing headache burden in patients with either episodic or chronic migraine (link to pg 5 in issue #3/Spring 2018). Since their release these MABs have been prescribed for many tens of thousands of patients. What have we learned from our clinical experience to date?

Mirroring their performance in the relevant research studies, all three MABs are generally well-tolerated. Aside from occasional injection site reactions and a low but discernible incidence of constipation in patients receiving erenumab (Aimovig), there has been no consistent pattern of additional side effects observed. One caveat: we have no long-term clinical experience with these MABs. While their mechanisms, sites of action and molecular nature are such that they should be safe, confirmation of that safety must await the test of time.

Are these MABs effective?  Yes and no.  Some migraine patients experience a dramatic reduction in headache burden within the first 1-2 months following initiation of therapy, and recent research data suggest that responders tend to experience further improvement as treatment continues. For most patients, evidence of a positive response will begin to emerge after the first or second treatment.  For other patients, however, the improvement may be less robust, and a significant percentage will experience no meaningful improvement whatsoever.

A number of related questions naturally follow:

  1. If a patient fails one MAB, will he/she potentially respond to another?  Answer: At this point we simply don’t know.  Suffice it to say that in patients who fail to respond after 2 or 3 treatments, a change in therapy typically is indicated… whether to another MAB or to a another type of therapy altogether.

  2. If one of these MABs is combined with another therapy for migraine prevention, will the combination have an additive effect in suppressing migraine?  Answer: again, we just don’t know.  At our own headache center we are following a number of patients who experienced a partial positive response to serial onabotulinumtoxinA (BotoxA) injection therapy and have continued that therapy following the addition of a MAB.  Generally speaking, both BotoxA and these MABs are believed to exert their therapeutic effect by acting upon a protein (calcitonin gene related peptide: CGRP) critical to head pain signal transmission within the circuitry that generates migraine (link to pg 7 in issue #2/Fall 2017).  Whether such combined therapy represents unnecessary and pointless duplication or a positive amplification of therapeutic effect remains unknown.

  3. Might there be better combinations of prophylactic therapy than BotoxA and a MAB?  Answer: possibly, but we currently lack the evidence required to provide a definitive answer.  Oral prophylactic therapies such as topiramate (Topamax, Trokendi, Qdexy) appear to possess multiple mechanisms of action for suppression of migraine, and while it makes sense that their use would be complementary to MAB therapy, it’s too early to make that claim with any degree of certainty.

  4. Have providers and patients experienced any difficulty in prescribing or obtaining these MABs?  Unfortunately, the answer is a resounding: Yes!  The three companies holding the patents for erenumab, galcanezumab and fremanezumab each have implemented patient assistance programs which at least theoretically will enable a majority of patients to obtain their particular MAB at little or no personal financial cost. In practice, however, the process of ensuring patients receive the MAB prescribed and do so in a manner that allows them to remain on a schedule of monthly administration has frequently proven to be unwieldy and even ineffective.  Provider experience has varied widely, and patient experience has been similarly inconsistent.  With time, the process hopefully will improve for all parties concerned.