Применение ласмидитана при острых приступах мигрени.

Shapiro RE et al

BACKGROUND:

In addition to the increased risk for cardiovascular (CV) disease and CV events associated with migraine, patients with migraine can also present with a number of CV risk factors (CVRFs). Existing treatment options can be limited due to contraindications, increased burden associated with monitoring, or patient avoidance of side effects. Safe and effective migraine treatment options are needed for patients with migraine and a history of CV or cerebrovascular disease or with increased risk for CV events. This analysis was designed to evaluate the safety and efficacy of oral lasmiditan, a selective serotonin 5-hydroxytryptamine 1F receptor agonist, in acute treatment of migraine attacks in patients with CVRFs.

METHODS:

SAMURAI and SPARTAN were similarly designed, Phase 3, randomized, double-blind, placebo-controlled trials in adults treating a single migraine attack with lasmiditan 50, 100, or 200 mg. Both studies included patients with CVRFs, and SPARTAN allowed patients with coronary artery disease, clinically significant arrhythmia, or uncontrolled hypertension. Efficacy and safety of lasmiditan in subgroups of patients with differing levels of CVRFs are reported. For efficacy analyses, logistic regression was used to assess treatment-by-subgroup interactions. For safety analyses, Cochran-Mantel-Haenszel test of general association evaluated treatment comparisons; Mantel-Haenszel odds ratio assessed significant treatment effects.

RESULTS:

In this pooled analysis, a total of 4439 patients received ≥1 dose of study drug. A total of 3500 patients (78.8%) had ≥1 CVRF, and 1833 patients (41.3%) had ≥2 CVRFs at baseline. Both trials met the primary endpoints of headache pain freedom and most bothersome symptom freedom at 2 h. The presence of CVRFs did not affect efficacy results. There was a low frequency of likely CV treatment-emergent adverse events (TEAEs) overall (lasmiditan, 30 [0.9%]; placebo, 5 [0.4%]). There was no statistical difference in the frequency of likely CV TEAEs in either the absence or presence of any CVRFs. The only likely CV TEAE seen across patients with ≥1, ≥ 2, ≥ 3, or ≥ 4 CVRFs was palpitations.

CONCLUSIONS:

When analyzed by the presence of CVRFs, there was no statistical difference in lasmiditan efficacy or the frequency of likely CV TEAEs. Despite the analysis being limited by a single-migraine-attack design, the lack of differences in efficacy and safety with increasing numbers of CVRFs indicates that lasmiditan might be considered in the treatment algorithm for patients with CVRFs. Future studies are needed to assess long-term efficacy and safety.

PubMed

Brandes JL et al

OBJECTIVES:

To address the need for long-term lasmiditan data, the GLADIATOR study evaluated the safety (primary) and efficacy (secondary) of lasmiditan for the intermittent, acute treatment of migraine attacks for up to 1 year.

METHODS:

In this prospective, randomized, open-label, Phase 3 study, patients who had completed either of two single-attack studies were offered the opportunity to be randomized 1:1 to lasmiditan 100 mg or 200 mg. Patients were asked to use lasmiditan as the first treatment for each new migraine attack of at least moderate severity. Assessments occurred at baseline and at prespecified time increments up to 48 hours after each dose of study drug using an electronic diary, and safety was assessed throughout the study. Migraine Disability Assessment (MIDAS) was assessed at each visit.

RESULTS:

As of the cut-off date for this interim analysis (6 March 2018), 1978 patients had received ≥ 1 lasmiditan dose and treated 19,058 migraine attacks. Overall, treatment-emergent adverse events (TEAEs) were similar to those in the single-attack studies and included dizziness (18.6%), somnolence (8.5%), and paresthesia (6.8%). The frequency of TEAEs generally decreased with subsequent attacks. No treatment-related serious adverse events and no cardiovascular TEAEs potentially due to vasoconstriction were observed. For both lasmiditan doses, efficacy measures were generally consistent over study quarters and treated attacks. Overall, across all treated attacks at 2 hours post-dose, pain freedom was observed in 26.9% of the attacks treated with lasmiditan 100 mg and 32.4% of the attacks treated with lasmiditan 200 mg. MIDAS total scores decreased over time.

CONCLUSIONS:

The interim results of this long-term study showed intermittent lasmiditan (100 mg and 200 mg) to be generally well tolerated and efficacious for the acute treatment of migraine over a 1-year period. Trial registration number: NCT02565186; clinicaltrials.gov/ct2/show/NCT02565186.

PubMed

For Immediate Release:

October 11, 2019

The U.S. Food and Drug Administration today approved Reyvow (lasmiditan) tablets for the acute (active but short-term) treatment of migraine with or without aura (a sensory phenomenon or visual disturbance) in adults. Reyvow is not indicated for the preventive treatment of migraine.

“Reyvow is a new option for the acute treatment of migraine, a painful condition that affects one in seven Americans,” said Nick Kozauer, M.D., acting deputy director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “We know that the migraine community is keenly interested in additional treatment options, and we remain committed to continuing to work with stakeholders to promote the development of new therapies for the acute and preventive treatment of migraine.” 

Migraine headache pain is often described as an intense throbbing or pulsing pain in one area of the head. Additional symptoms include nausea and/or vomiting and sensitivity to light and sound. Approximately one-third of individuals who suffer from migraine also experience aura shortly before the migraine. An aura can appear as flashing lights, zig-zag lines, or a temporary loss of vision. Migraines can often be triggered by various factors including stress, hormonal changes, bright or flashing lights, lack of food or sleep, and diet. Migraine is three times more common in women than in men and affects more than 10% of people worldwide.

The effectiveness of Reyvow for the acute treatment of migraine was demonstrated in two randomized, double-blind, placebo-controlled trials. A total of 3,177 adult patients with a history of migraine with and without aura treated a migraine attack with Reyvow in these studies. In both studies, the percentages of patients whose pain resolved and whose most bothersome migraine symptom (nausea, light sensitivity, or sound sensitivity) resolved two hours after treatment were significantly greater among patients receiving Reyvow at all doses compared to those receiving placebo. Although patients were allowed to take a rescue medication two hours after taking Reyvow, opioids, barbiturates, triptans and ergots were not allowed within 24 hours of the study drug’s administration. Twenty-two percent of patients were taking a preventive medication for migraine.

There is a risk of driving impairment while taking Reyvow. Patients are advised not to drive or operate machinery for at least eight hours after taking Reyvow, even if they feel well enough to do so. Patients who cannot follow this advice are advised not to take Reyvow. The drug causes central nervous system (CNS) depression, including dizziness and sedation. It should be used with caution if taken in combination with alcohol or other CNS depressants.

The most common side effects that patients in the clinical trials reported were dizziness, fatigue, a burning or prickling sensation in the skin (paresthesia), and sedation.

The FDA granted the approval of Reyvow to Eli Lilly and Company.     

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.