Anticalcitonin Gene-Related Peptide Agents Effectively Prevent Migraines

Anticalcitonin gene-related peptide agents, delivered in monthly or daily doses, can effectively combat migraine with few side effects, according to research published in the  Clinical Journal of Pain.

To address the lack of research comparing the relatively new oral anticalcitonin gene-related peptide (CGRP) agent atogepant with injected CGRP monoclonal antibodies (mAbs) in preventing migraine, a research team conducted a network meta-analysis of the efficacy and safety of different doses of atogepant and CGRP mAbs.

The researchers identified 24 articles for analysis to identify all randomized controlled trials (RCTs) published through May 2022 that included patients diagnosed with episodic or chronic migraine who were treated with erenumab, fremanezumab, eptinezumab, galcanezumab, atogepant, or placebo. Outcomes included the reduction in the number of days per month during which patients experienced migraine, the 50% response rate, and the number of adverse events (AEs) they experienced. Risk of bias was assessed by using the Cochrane Collaboration tool, which revealed no substantial publication bias in the analysis.

The researchers found that, although all agents studied were more effective than placebo in preventing migraine to a statistically significant degree, monthly fremanezumab 225 mg, was the most effective in reducing the number of days during which migraine was experienced (standardized mean difference [SMD], -0.49; 95% confidence interval [CI], -0.62, -0.37) and in producing a 50% response rate (relative risk [RR], 2.98; 95% CI 2.16, 4.10). In contrast, monthly erenumab 140 mg, proved the best choice for reducing the number of days during which medication was required for acute migraine (SMD −0.68; 95% CI −0.79, −0.58). 

Regarding migraine type, monthly fremanezumab 225 mg, was the most effective anticalcitonin gene-related peptide agent evaluated for episodic migraines, whereas monthly erenumab 140 mg, was best for chronic migraines.

Although eptinezumab is the only intravenous agent with a rapid onset of action, it is considerably less effective than fremanezumab and erenumab in reducing the number of days during which migraine is experienced as well as in achieving a 50% response rate and in reducing the number of days during which medication was required for acute migraine.

Galcanezumab, 120 mg, had greater efficacy than most anticalcitonin gene-related peptide agents but a significantly higher incidence of AEs than placebo. Moreover, because high-dose galcanezumab increased the incidence of serious AEs, the researchers do not recommend its use.

Although daily atogepant, 60 mg, ranked fourth in its reduction in the number of days during which patients experienced migraine and in the 50% response rate, this agent was safer than its comparators. “There was no signal of hepatotoxicity with atogepant in the RCT trials [sic] we included, and the liver safety profile has no significant difference when compared with placebo,” the researchers explain. As a result, they recommended atogepant as an alternative for migraine prevention in those who cannot tolerate the AEs associated with injected anticalcitonin gene-related peptide agents.

Although no significant difference in the rate of discontinuation owing to adverse events was found between the treatments evaluated and placebo, monthly fremanezumab 225 mg, monthly erenumab 140 mg, and daily atogepant 60 mg, had fewer side effects than the other agents studied. 

Limitations of this analysis included potential skewing because of inclusion and exclusion criteria, the brevity of the trials included, and the range of durations of the studies evaluated.

“The results of this study are also anticipated to provide a foundation for evidence-based practice and educate patients, doctors, and guidelines writers on the relative benefits of various migraine preventive drugs,” according to the researchers. “Monthly fremanezumab 225 mg, monthly erenumab 140 mg, and daily atogepant 60 mg, may be effective interventions with acceptable safety.”