IMPORTANCENew therapeutic classes of migraine-specific treatment have been developed, including 5-hydroxytryptamine 1F receptor agonists (lasmiditan) and calcitonin gene-related peptide antagonists (rimegepant and ubrogepant). OBJECTIVE To compare outcomes associated with the use of lasmiditan, rimegepant, and ubrogepant vs triptans for acute management of migraine headaches. DATA SOURCES The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to March 5, 2020. STUDY SELECTION Double-blind randomized clinical trials examining current available migrainespecific acute treatments were included.
DATA EXTRACTION AND SYNTHESISThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was applied to extract the data according to a predetermined list of variables of interest, and all network meta-analyses were conducted using a randomeffects model.
MAIN OUTCOMES AND MEASURESThe primary outcome was the odds ratio (OR) for freedom from pain (hereafter referred to as pain freedom) at 2 hours after the dose, and the secondary outcomes were ORs for pain relief at 2 hours after the dose and any adverse events. RESULTS A total of 64 randomized clinical trials were included (46 442 participants; 74%-87% women; age range, 36-43 years). Most of the included treatments were associated with reduced pain at 2 hours compared with placebo. Most triptans were associated with higher ORs for pain freedom at 2 hours compared with lasmiditan (range: OR, 1.72 [95% CI, 1.06-2.80] to OR, 3.40 [95% CI, 2.12-5.44]), rimegepant (range: OR, 1.58 [95% CI, 1.07-2.33] to OR, 3.13 [95% CI, 2.16-4.52]), and ubrogepant (range: OR, 1.54 [95% CI, 1.00-2.37] to OR, 3.05 [95% CI, 2.02-4.60]). Most triptans were associated with higher ORs for pain relief at 2 hours compared with lasmiditan (range: OR, 1.46 [95% CI, 1.09-1.96] to OR, 3.31 [95% CI, 2.41-4.55]), rimegepant (range: OR, 1.33 [95% CI, 1.01-1.76] to OR, 3.01 [95% CI, 2.33-3.88]), and ubrogepant (range: OR, 1.38 [95% CI, 1.02-1.88] to OR, 3.13 [95% CI,). The comparisons between lasmiditan, rimegepant, and ubrogepant were not statistically significant for both pain freedom and pain relief at 2 hours. Lasmiditan was associated with the highest risk of any adverse events, and certain triptans (rizatriptan, sumatriptan, and zolmitriptan) were also associated with a higher risk of any adverse events than the calcitonin generelated peptide antagonists. (continued) Key Points Question When compared with triptans, are 5-hydroxytryptamine 1F receptor agonists (ie, ditans) and calcitonin gene-related peptide antagonists (ie, gepants) associated with reduced pain and fewer adverse events for acute management of migraine headache? Findings This systematic review and network meta-analysis including 64 randomized clinical trials with a total of 46442 participants found that triptans, ditans, and gepants were associated with reduced pain at 2 hours compared with placebo; however, most triptans were associated with reduced pain when compared with ...