Comparison of New Pharmacologic Agents With Triptans for Treatment of Migraine

Abstract

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 ...

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

“…In the largest of these NMAs, Yang et al [ 30 ] included a total of 64 double-blind RCTs with the aim of comparing the efficacy of lasmiditan, rimegepant, ubrogepant, triptans and other currently available migraine-specific acute treatments. In comparisons between lasmiditan (50 and 100 mg), rimegepant (75 mg ODT/tablet not differentiated) and ubrogepant (50 and 100 mg), no statistically significant differences in the odds of achieving pain freedom or pain relief at 2 hours were seen.…”

“…In the absence of such data, network meta-analysis (NMA) offers a way of comparing interventions simultaneously in a single analysis. To date, three NMAs have been published, comparing the efficacy of lasmiditan, rimegepant and ubrogepant – those of Johnston et al 2022 [ 28 ], Agboola et al 2020 [ 29 ] and Yang et al 2021 [ 30 ]. Since publication of these NMAs, new key data/evidence for lasmiditan have become available from the registration studies CENTURION [ 17 ] and MONONOFU [ 18 ].…”

CGRP Regulates Nucleus Pulposus Cell Apoptosis and Inflammation via the MAPK/NF‐κB Signaling Pathways during Intervertebral Disc Degeneration

“…Therefore, the CGRP receptor can be a therapeutic target for IVDD. Rimegepant, also known as BMS-927711, is a novel small molecular compound that potently antagonizes the CGRP receptor [ 60 ]. Our results indicated that Rimegepant could inhibit the adverse effects of CGRP on human NP cells in vitro.…”

Gepants — a long way to cure: a narrative review

“…After 40 years since discovering CGRP, the gepants, antagonists of the CGRPr, are finally available for clinical use. RCTs demonstrated gepants’ efficacy in treating acute attacks to obtain 2 h pain freedom in about 20% of patients and pain relief in about 60% of them, with a more favorable safety profile than triptans [ 75 ]. Gepants were also the first oral agents specifically designed to prevent migraine.…”