Lasmiditan for Acute Treatment of Migraine in Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Abstract

The US Food and Drug Administration has approved orally administered 100-mg and 200-mg doses of lasmiditan for the acute treatment of migraine, with or without aura. Having a unique mechanism of action, lasmiditan is the first and only Food and Drug Administration-approved serotonin 5-HT1F receptor agonist. The objective of this study was to systematically evaluate the efficacy and safety of lasmiditan for the acute treatment of migraine in adult patients. We systematically searched PUBMED, EMBASE, and Cochrane Library databases. Any relevant articles published before 3 March, 2020 were collected. Inclusion criteria were: (1) randomized clinical trials; (2) enrolled adult participants diagnosed with migraine; (3) compared lasmiditan at 100mg or 200mg with placebo; (4) enrolled more than 100 participants; and (5) provided any available data for predefined primary or secondary outcomes. Three high-quality, multi-centered randomized clinical trials with 4506 patients in total were included. We found that the use of lasmiditan was related to a significantly increased rate of pain freedom at 2h post-dose with 31.60% patients achieving freedom of pain in the lasmiditan group compared with 17.55% patients in the placebo group (relative risk [RR] 1.80 [95% confidence interval (CI) 1.34-2.42]), with no significant heterogeneity. In addition, lasmiditan is reported to significantly increase the rate of absence of the most bothersome symptoms at 2h compared with the placebo group with no significant heterogeneity (lasmiditan, 42.82%; placebo, 30.38%; RR 1.44 [95% CI 1.03-2.01], I2 = 0%). With regard to the safety endpoints, compared with the placebo group, participants in the lasmiditan group had a higher rate of fatigue, paresthesia, and somnolence (fatigue: lasmiditan, 1.94%; placebo, 0.24%; RR 7.96 [95% CI 0.4-158.86]; paresthesia: lasmiditan, 6.91%; placebo, 1.56%; RR 4.46 [95% CI 1.54-12.93], somnolence: lasmiditan, 5.9%; placebo, 2.15%; RR 2.76 [95% CI, 1.49-5.11]) with low heterogeneity. A subgroup analysis demonstrated that without safety differences, participants who received the 200-mg dose had a higher percentage of freedom of pain at 2h and sustained pain relief at 2-24h compared with the 100-mg dose (freedom of pain at 2h: lasmiditan, 34.53%; placebo, 28.67%; RR 1.2 [95% CI 1.04-1.38]; lasmiditan, 20.62%; placebo, 16.33%; RR 1.26 [95% CI 1.19-1.34]), with low heterogeneity for both outcomes (I2 = 0%). In this meta-analysis, the use of lasmiditan as an acute treatment for episodic migraine in adults led to a greater percentage of freedom of pain and the absence of the most bothersome symptoms at 2h post-dose. Lasmiditan 200mg had superior efficacy to 100-mg dose without a significantly increased risk for adverse events.