Ubrogepant relieves early migraine symptoms and may help prevent full-blown attacks

Ubrogepant relieves early migraine symptoms and may help prevent full-blown attacks

Treat migraines before the pain begins: New research shows ubrogepant relieves pre-onset symptoms, offering hope to millions seeking earlier and more effective relief.

Recent exploratory analysis from the Phase 3 Prodrome trial shows that ubrogepant, a calcitonin gene-related peptide receptor antagonist, administered in the initial phase of a migraine attack, can improve common prenatal symptoms, including fatigue, light and sound sensitivity, sore throat, and dizzy spells. A detailed report will be published in the JournalNatural medicine.

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Almost a third of participants who recognized prodromal symptoms reported moderate to severe functional disability due to symptoms such as cognitive impairment or fatigue, highlighting the need for early intervention.

Migraine is a common neurological disorder characterized by recurrent attacks of moderate to severe headaches and other symptoms of brain dysfunction. Migraine has four distinct but often overlapping phases, including premonitory (prodrome), aura, headache, and postdrome phases.

The symptoms of the preconception phases are broadly divided into three groups: cognitive impairments, characterized by concentration or thinking and fatigue; homeostatic dysfunction characterized by food cravings; and headache phase-associated symptoms, including sensitivity to light and sound.

Premonitory symptoms are highly predictive of approaching headaches and are associated with activation of the hypothalamus region of the brain. These findings, along with others discussed in the paper, support the understanding of migraine attacks that may originate in the central nervous system. The identification of the role of the calcitonin gene-related peptide as a causative neurotransmitter associated with migraine attacks has offered the opportunity to explore migraine pathophysiology. Small molecule inhibitors of the calcitonin gene-related peptide receptor have shown promising results in preventing migraine attacks.

The prodromic Phase 3 multicenter, randomized, double-blind, placebo-controlled, crossover study was designed to evaluate the efficacy of ubrogepant, a calcitonin gene-related peptide receptor antagonist, in preventing the development of headache and resolving premonitory phase symptoms. This article focuses on an exploratory analysis of its effects on premonitory symptoms.

Experimental design

Brain-building studies cited in the study suggest that relief of prodromal symptoms by ubrogepant may be associated with central nervous system effects, with hypothalamic activation patterns observed during migraine pre-monitoring phases.

The study recruited migraine sufferers who could reliably identify migraine attacks with at least 75% of headache cases occurring in 1–6 hours. Qualifying prodromal events were defined by the presence of preconception phase symptoms, which the participant would confidently be followed by 1–6 hours of headache.

Participants were randomly assigned to two groups. In one group, participants received a placebo drug to treat the first qualifying precongestion and ubrogepant 100 mg to treat the second qualifying precongestion. In another group, participants received ubrogepant 100 mg to treat the first qualifying premonitory event and placebo medication to treat the second qualifying event. The two treatments were separated by a minimum 7-day washout period.

Experimental results

The study included 480 participants for safety analysis and 477 participants for efficacy analysis. The safety population had a mean age of 42.3 years and was predominantly female (87.7%) and white (88.1%), which may account for generalizability. The most common premature symptoms identified at baseline before treatment were sensitivity to light and sound, fatigue, neck pain and dizziness.

Both drugs (ubrogepant and placebo) were administered in the pre-mission phase of migraine, and results were recorded over a 48-hour period.

Effectiveness analysis

Cognitive symptoms such as “brain fog” resolved more quickly with ubrogepant: difficulty thinking improved within 6 hours, while concentration problems showed improvement as early as 1 hour after the dose.

The exploratory efficacy analysis, for which the paper provides precise percentages, odds ratios and confidence intervals, found lack of photosensitivity in approximately 19% and 12% of ubrogepant- and placebo-treated events at 2 hours post-treatment. a lack of fatigue in approximately 27% and 16% and the absence of neck pain in approximately 28% and 15% of ubrogepant and placebo events, respectively, at 3 hours post-treatment; an absence of sound sensitivity in approximately 50% and 35% of respective events at 4 hours post-treatment; and the absence of dizziness in approximately 88% and 82% of the respective events at 24 hours after treatment.

Among symptoms of cognitive impairment, concentration difficulties resolved in approximately 8% and 2% of ubrogepant- and placebo-treated events, respectively, at 1 hour after treatment, and thinking difficulties resolved in approximately 56% and 41% of respective events after treatment. Additionally, rescue medication use within 24 hours of dosing was lower in UBROGEPANT-treated events (21.7%) compared to placebo-treated events (39.4%).

Security analysis

Treatment-emergent treatment-emergent adverse events (TEAEs) were identified in 9% of placebo-treated events and 13% of ubrogepant-treated events. Overall, 12% of placebo-treated events and 17% of ubrogepant-treated events were reported to have treatment losses, regardless of perceived relationship to treatment. The most common adverse events (≥2%) following placebo and ubrogepant administration were nausea, fatigue, dizziness, and somnolence (sleepiness). None of these events were serious or resulted in discontinuation of studies.

Meaning

The study suggests that ubrogepant may be a therapeutic drug that can help resolve the deactivation of symptoms that occur in the premature phase of migraine. During this phase, ubrogepant may improve common preconception symptoms, with possible improvement as early as one hour after treatment.

The symptoms of the preconception phases are very predictable for impending headaches. Existing evidence shows that a significant proportion of migraine sufferers can recognize these symptoms the day before their headache. Therefore, treatments aimed at resolving these symptoms have high potential to prevent the onset of headaches.

The study censored data from participants who used rescue medications, ensuring that results were not confounded by painkiller medications—a rigor that strengthened the validity of the symptom resolution findings.

As mentioned by researchers, greater awareness of the clinical symptomatology of the pre-onset phase as well as the availability of effective treatment offers a great opportunity to improve the treatment of acute migraine. The paper also emphasizes that reversing these symptoms with a CGRP receptor antagonist such as ubrogepant highlights the importance of the brain in migraine pathophysiology and suggests that targeting central nervous system mechanisms could be a fruitful avenue for new therapeutics.

The primary objective of the Prodrome study was to evaluate the effectiveness of ubrogepant in preventing the onset of headache following administration during the premonition phase of a migraine attack. The evaluation of the effectiveness of ubrogepant in resolving preconception symptoms was an exploratory analysis of additional endpointsNatural medicinePaper. The authors note that these analyzes were not controlled for multiple comparisons, highlighting the need for additional studies specifically designed to evaluate the effect of acute treatment on premonitory symptoms.

In addition, subjects were instructed to consume ubrogepant if they recognized preconception symptoms and were confident that a headache would follow within 1 to 6 hours. However, the study did not analyze differences in symptom resolution between participants who did and did not develop headaches. These parameters should be considered in future studies.

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