The Effect and Safety of 5-HT1F Receptor Agonist Lasmiditan on Migraine: A Systematic Review and Meta-Analysis

Abstract

Background. Migraine has a great impact on public health. Current acute therapies do not satisfy all migraineurs. The novel serotonin 5-HT1F receptor agonist appears more promising for aborting migraine attacks. Objective. To evaluate the clinical efficacy and safety of lasmiditan in treating acute migraine attacks. Methods. The literature search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) which assessed the effect and safety of lasmiditan on migraine. The risk of bias was assessed using the Cochrane Collaboration’s risk of bias tool. Results were extracted and pooled as risk ratios (RRs) with a fixed or random-effects model. Results. Based on the four included RCTs, pooled estimates showed that lasmiditan with the 50 mg, 100 mg, and 200 mg doses was superior to placebo at 2 h after the first dose in terms of pain freedom, absence of migraine-associated symptoms, headache relief, no/mild disability, and global impression of change (very much/much better) (RRs ranged from 1.13 to 1.96), except for nausea-free and vomiting-free. Both lasmiditan 100 mg and 200 mg resulted in significantly fewer patients using rescue medication (100 mg: RR = 0.75 , 95% CI (0.61, 0.92), P = 0.007 ; 200 mg: RR = 0.81 , 95% CI (0.66, 0.99), P = 0.04 ) at 2-24 h postdose, compared with placebo. Safety data showed that the proportion of patients reporting at least one treatment-emergent adverse event (TEAE) and the incidence of most common TEAEs such as dizziness, paresthesia, fatigue, somnolence, and nausea was higher in the lasmiditan groups (50 mg, 100 mg, and 200 mg), compared with placebo. There was no significant difference between lasmiditan and placebo in terms of cardiovascular-related TEAEs ( RR = 2.75 , 95% CI (0.81, 9.37), P = 0.11 ). Compared with lasmiditan 100 mg, lasmiditan 200 mg was more effective in pain freedom at 2 h after the first dose ( RR = 0.83 , 95% CI (0.74, 0.94), P = 0.004 ) but associated with a higher risk of reporting at least one TEAE ( RR = 0.88 , 95% CI (0.81, 0.96), P = 0.006 ). Conclusions. Lasmiditan with the 50 mg, 100 mg, and 200 mg doses are effective and safe in acute migraine treatment. Lasmiditan 200 mg is more effective than lasmiditan 100 mg in pain freedom, while lasmiditan 100 mg is better tolerated in the short-term follow-up. Further larger sample-size RCTs are required to verify the applicability and tolerability in the long term.

Profile of Lasmiditan in the Acute Treatment of Migraine in Adults: Design, Development, and Place in Therapy

“…Several meta-analyses have been published based on data from the previously mentioned clinical trials which have demonstrated that lasmiditan is effective at relieving acute migraine pain compared with placebo [47][48][49] with several demonstrating that the 200 mg dose is more effective than the 100 mg dose. [50][51][52] When compared to triptans, lasmiditan has shown lower odds ratios for pain freedom at 2 hours compared with most triptans (OR 1.72, 95% CI 1.06-2.80 to OR 3.40 95% CI 2.12-5.44) as well as pain relief at 2 hours (OR 1.46, 95% CI 1.09-1.96 to OR 3.31, 95% CI 2.41-4.55). Lasmiditan has also been found to have nonsignificant differences in odds ratios compared with small molecule anti-CGRP gepant rescue medications such as ubrogepant and rimegepant for both pain freedom and pain relief.…”