gms | German Medical Science

Introduction: More than 10% of the global population is said to be affected by migraine attacks, which can severely impair quality of life. Furthermore, migraine is regarded as one of the major causes of disability worldwide. Two new generations of drugs, i.e., ditans and gepants, have been developed for the treatment of migraine attacks. The ditan, serotonin 5-HT1F receptor agonist, lasmiditan has been studied at the doses of 50, 100 and 200mg. Gepants, calcitonin gene-related peptide (CGRP) receptor antagonists, are represented by the drugs rimegepant (orally available at the dose of 75mg) and ubrogepant (orally available at the doses 50 and 100mg, while also studied at 25mg). Clinical trials for these new drugs have been published recently. The aim of this study was to analyze and compare the efficacy and safety of these new drugs for the acute treatment of migraine in adult patients by using phase 3 randomized controlled trials (RCTs) for a network meta-analysis [1].

Methods: A systematic search was conducted in MEDLINE via PubMed, Embase and The Cochrane Register of Controlled Trials. Phase 3 RCTs studying lasmiditan, rimegepant or ubrogepant for the acute treatment of adult migraine patients were included. Two primary efficacy endpoints were analyzed, namely pain freedom at two hours, and freedom from most bothersome symptom at two hours. Treatment emergent adverse events (TEAEs) were regarded as one of the main outcomes for safety and tolerability. Frequentist random effects network meta-analyses with in addition pairwise meta-analyses were performed for all outcomes. Odds ratios (ORs) with 95% confidence intervals (CIs) for the comparison to placebo were estimated and reported.

Results: After screening, seven studies could be included for analysis in the network meta-analysis with in total 12,859 patients. In terms of the two primary efficacy endpoints, all treatments differed significantly from placebo. The largest odds ratio for the outcome pain freedom at two hours was estimated for lasmiditan 200mg (OR 2.88, 95% CI [2.22, 3.73]), and the second largest for lasmiditan 100mg (OR 2.28, 95% CI [1.75, 2.96]). The results for the outcome freedom from most bothersome symptom at two hours were similar for most treatments with estimated ORs slightly above 1.60, except for the small doses of lasmiditan (50mg) and ubrogepant (25mg) with estimated ORs of only 1.30 and 1.36. The ORs for TEAEs were largest for all doses of lasmiditan, with the largest effect estimated for the 200mg dose (OR 4.62, 95% CI [3.73, 5.72]).

Discussion and Conclusion: Lasmiditan 200mg was estimated to be the most efficacious of the studied migraine attacks treatments, but with the worst tolerability profile. Rimegepant and ubrogepant were less efficacious although better tolerated. This network meta-analysis permitted the analysis and comparison of the safety and efficacy of new treatments for migraine attacks. The results are based on few studies with possible heterogeneity and limited representativeness of the study populations. To confirm our results, more studies including adequate head-to-head clinical trials are needed.

The authors declare that they have no competing interests.

The authors declare that an ethics committee vote is not required.