Migraine Treatment of the Month: Qulipta Re-Visited
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As we have discussed many times before in Migraineur, “migraine” is the constellation of symptoms that result from a biological circuit within the nervous system which – like all nervous system circuits – involves electrochemical transmission of a signal…a head pain sign signal in the case of migraine. The “chemicals” involved in this transmission are primarily neuropeptides (nervous system proteins), and one of the major neuropeptides active in the migraine circuitry is calcitonin gene related peptide (CGRP).
Atogepant (Qulipta) is a “gepant” that blocks the action of CGRP and essentially “short-circuits the circuit”. Qulipta was FDA-approved as a prevention therapy for episodic and chronic migraine (EM and CM) in September 2021, and we previously featured the medication in our Winter 2022 issue. Over the last 3 years the medication’s use has expanded dramatically, and due to both this accumulated clinical experience and new research involving the drug we felt Qulipta was worth re-visiting.
Qulipta’s effectiveness as a prevention therapy for EM has been clearly established, and Qulipta represents a welcome addition to the growing arsenal of similarly attractive EM therapies. It is CM, however, that accounts for a disproportionate share of the public health burden imposed by migraine generally, and until relatively recently we lacked any evidence-based therapy for suppression of CM. Along with onabotulinumtoxinA (BotoxA), 3 subcutaneously self-injected anti-CGRP monoclonal antibodies (mabs) and one intravenously infused anti-CGRP mab, Qulipta is one of the “Big 6” therapies for suppression of CM that possesses a strong evidence base for that indication, is safe, is typically well-tolerated and is clearly effective in a high proportion of CM patients.
This magazine’s editor served as a clinical investigator in PROGRESS, the phase 3 research trial that evaluated Qulipta’s safety and effectiveness in suppressing CM. While the trial was placebo-controlled and double-blind (ie, neither the investigators nor the patients/research subjects knew whether they had been randomized to placebo or Qulipta) it was quite obvious almost from the start that an unusually high proportion of the subjects were experiencing a significant reduction in headache frequency quite soon after starting the study drug. When the study was completed and the “blind” was lifted, the results clearly demonstrated Qulipta to be superior to placebo for treating CM. Also significant was the finding that in those subjects destined to respond to Qulipta the response typically was evident within the first month of treatment.
In a paper recently published in the journal Neurology, Lipton and colleagues evaluated the results from the two phase 3 trials involving Qulipta for EM and the PROGRESS trial involving CM. In those trials, the superiority of Qulipta over placebo was evident as early as the first day following initiation of treatment and was more effective than placebo in reducing weekly “migraine days” during each of the first 4 weeks following initiation of treatment.
These are findings of high clinical relevance for both patients and healthcare providers. That an oral prevention therapy can be effective so rapidly in treating migraine – and especially CM – is news that is most welcome.
Which is better for suppressing CM: Qulipta, a subcutaneously self-injected or intravenously administered anti-CGRP mab or BotoxA? In the absence of active comparator (i.e., head-to- head) clinical trials, about the most that can be said at this point is that all of these therapies are safe and effective for treating CM.
Will Qulipta prove to be effective in CM patients who have failed to respond to an anti-CGRP mab or BotoxA? Again, no one knows.
Might certain combinations of these “Big 6” therapies for CM prove to be more effective than monotherapy with only one? This, too, remains uncertain, but there is some very preliminary evidence that initiating “prophylactic polytherapy” by adding Qulipta to the treatment regimen of CM patients who have experienced a partial positive response to BotoxA may further improve treatment response in a high percentage.
Especially in dealing with a disorder as prevalent and as distressingly effective in reducing quality of life as is CM, it’s awfully nice to have options. For patients with CM (or EM) who prefer an oral therapy for migraine prevention and are seeking a rapid onset of therapeutic effect, Qulipta represents a very attractive option.
