Relative efficacy of lasmiditan versus rimegepant and ubrogepant as acute treatments for migraine: network meta-analysis findings

Abstract

Background In the absence of head-to-head trials, comprehensive evidence comparing onset of efficacy of novel agents for acute treatment of migraine is lacking. This study aimed to explore the relative efficacy of lasmiditan (serotonin [5-hydroxytryptamine] 1F receptor agonist) versus rimegepant and ubrogepant (calcitonin gene-related peptide antagonists) for the acute oral treatment of migraine through network meta-analysis (NMA). Methods Data included in the NMA were identified through a systematic literature search (conducted April 2018, updated May/December 2020) of phase II–IV, randomised controlled trials (RCTs) in adults with chronic/episodic migraine with/without aura. Treatments included: lasmiditan 50, 100, 200 mg; rimegepant 75 mg; ubrogepant 25, 50, 100 mg. Pairwise treatment comparisons from Bayesian fixed-effect/random-effects NMA, adjusted by baseline risk where appropriate, were conducted. Comparisons were reported as odds ratios with 95% credible intervals. Early-onset efficacy endpoints included: pain freedom at 2 hours and pain relief at 1 and 2 hours. Adverse drug reaction (ADR) profiles were summarised. Heterogeneity and inconsistency in the network were explored; sensitivity analyses investigated robustness of findings. Results Across 12 RCTs included in the base case, females represented >80% of included patients (mean age 37.9–45.7 years). Odds of achieving both pain freedom and pain relief at 2 hours were higher with lasmiditan 100 and 200 mg versus rimegepant 75 mg and ubrogepant 25 and 50 mg. Results for pain relief at 1 hour were consistent with those at 2 hours, but fewer comparisons were available. There were no statistically significant differences between lasmiditan 50 mg and ubrogepant or rimegepant for any outcome. Sensitivity analyses were in the same direction as base case analyses. Most commonly reported ADRs (incidence ≥2%) were: dizziness, fatigue, paraesthesia, sedation, nausea/vomiting and muscle weakness with lasmiditan; nausea with rimegepant; and nausea, somnolence and dry mouth with ubrogepant. Conclusions The efficacy findings of this indirect comparison indicate that lasmiditan 100 mg or 200 mg might be an appropriate acute treatment option for patients with migraine seeking a fast onset of action. Differently from rimegepant and ubrogepant, lasmiditan use is associated with mainly neurological events, which are mostly mild or moderate in severity and self-limiting. 350/350 words

Efficacy, safety and indirect comparisons of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine: A systematic review and network meta-analysis of the literature

“…Rimegepant and lasmiditan 200 mg were superior to other interventions for sustained pain freedom at 24 hours, whereas pain relief at two hours had the highest odds to be achieved compared to placebo with the higher doses of lasmiditan and with rimegepant. These efficacy results are similar to those of a recent network meta-analysis comparing lasmiditan with rimegepant and ubrogepant (30).…”

The pharmacotherapeutic management of episodic and chronic migraine with gepants

“…A network meta-analysis aimed to indirect comparison of lasmiditan (50, 100, and 200 mg) versus rimegepant (75 mg) and ubrogepant (25, 50, and 100 mg) in acute treatment for migraine resulted no statistically significant differences were demonstrated in 50 mg lasmiditan and ubrogepant and rimegepant for pain freedom at 2 hours and pain relief at 1 and 2 hours post-dose. Gepants showed less AEs compared to lasmiditan [57].…”

One Health for Headaches: A Clinical Scientist Residence Project

“…This project envisages that, alongside the theoretical phase, a care model design that is compatible with local facilities can be implemented for a short stay. The theoretical phase can benefit from several teaching aids, such as headache book series [ 15 ] and management guidelines that can, at different levels of intervention, allow for the use of drugs that are locally available, from the standard of care up to the most recent drugs that target calcitonin-gene-related peptide [ 17 , 18 , 19 , 20 ].…”