Migraine Treatment of the Month: Atogepant (Qulipta)
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The nervous system is a complex collection of interactive electronic circuits that conduct communication signals along insulated wires that are called axons. As with any nervous system circuit, the biologic circuit that produces migraine headache conducts signal - in this case the signal of head pain - via electrochemical transmission. Put simply, an electronic signal travels down an axon, reaches a certain point, causes the release of a chemical, and that chemical interacts with its receptor either to pass the head pain signal along or to complete the circuit and produce the desired result…or in the case of migraine headache, the not so desired result.
While many different chemicals, most of them peptides (proteins), participate in migraine’s circuitry, two of the most important chemical proteins within the circuit are serotonin and calcitonin gene-related peptide (CGRP). If one can block the contribution of either protein to the conduction of head pain signal, the sensitivity of the migraine circuit will be diminished, and the circuit’s ability to produce headache consequently will decrease. It’s like turning a light off by pressing a switch or turning down its brightness by adjusting a rheostat.
At present there are two major classes of anti-CGRP medications for migraine treatment: the monoclonal antibodies and the “gepants” (rimigepant/Nurtec, ubrogepant/Ubrelvy and, now, atogepant/Qulipta).
The anti-CGRP monoclonal antibodies (Mabs) are indicated for prevention/suppression of migraine and not for acute migraine treatment. Ubrelvy is indicated for acute migraine treatment only. Nurtec occupies the unique position of being indicated for both acute migraine treatment and prevention of episodic migraine.
ADVANCE, the well-designed multi-center trial that evaluated Qulipta‘s safety, tolerability and effectiveness in the prevention of episodic migraine, demonstrated the medication to be safe, tolerable and robustly effective in reducing headache burden and migraine-related disability. Perhaps most striking, in those research subjects with episodic migraine who were destined to respond to Qulipta, a positive response often was observed within the first 1 to 2 weeks of initiating treatment. This tendency for early treatment response is not common amongst oral medications used for migraine prevention, and if this finding so clearly demonstrated in the ADVANCE study extends to general clinical practice, it will be attractive to both migraine patients and the physicians who care for them. Waiting weeks to months to determine whether or not a medication may be effective can be a tedious and frustrating process, and for a patient to experience the beginnings of a positive response so early in treatment can serve only as positive reinforcement for continuing the treatment.
Qulipta is available in 10, 30 and 60 mg dose formulations, each to be taken as one dose daily.
To put things in perspective, and rapidity of response aside, there is at most one other oral medication for prevention of episodic migraine, Nurtec, that is as well tolerated as Qulipta, as specific in its mechanism of action within the migraine circuitry and possessed of such a strong scientific evidence base for its use. A large scale clinical trial evaluating Qulipta‘s effectiveness in treating chronic migraine was just completed, and its results should be forthcoming soon.
Which is better: Qulipta or a subcutaneously self-injected or intravenously administered anti-CGRP mab? How about Qulipta versus Nurtec? or Qulipta versus older therapies such as topiramate? In the absence of active comparator (ie, head-to-head) clinical trials, about the most that can be said at this point is that all of these medications are safe and effective for migraine prevention. Topiramate can be notoriously difficult to tolerate for a variety of reasons, but all of the others are generally well-tolerated by most patients.
Will Qulipta prove to be effective in patients who have failed to respond to an anti-CGRP Mab or Nurtec? Again, no one knows, but to extrapolate from the admittedly preliminary data concerning the anti-CGRP Mabs, an improvement in treatment response may be reported by patients who are switched from one anti-CGRP prevention medication to another.
Especially in dealing with a disorder as prevalent and as clinically varied as migraine, it’s awfully nice to have options. For patients with episodic migraine who prefer an oral therapy for migraine prevention and for whom tolerability with a low chance of significant adverse side effects is important, Qulipta represents a very attractive new option.
