Migraine
Clarissa Chan, PharmD
A systematic review and meta-analysis by Yang and colleagues, published in JAMA Open Network in October 2021, found that 5-HT1F receptor agonists or “ditans” (lasmiditan) and calcitonin gene-related peptide antagonists or “gepants” (rimegepant and ubrogepant) were not as effective in reducing pain 2 hours post-dose as compared to triptans. However, the study findings concluded gepants were less likely to cause mild to moderate adverse events compared to triptans.
“This was a decently performed meta-analysis of the major players approved for acute migraine treatment, although lesser players [like NSAIDs] were excluded,” said Frederick G. Freitag, DO, FAHS, professor emeritus at Medical College of Wisconsin’s Department of Neurology, who was not involved with the research.
Although triptans are regarded as the standard of care in acute migraine treatment due to their efficacy and tolerability, they are only known to be effective in 27% to 30% of patients treated. Investigating newer pharmacotherapies versus current gold-standard acute therapy options could help health care practitioners better treat migraine.
Study findings
Yang and colleagues’ review analyzed 64 double-blind randomized clinical trials obtained from the Cochrane Register of Controlled Trials, Embase, and PubMed databases between inception to March 5, 2020. The review included 46,442 participants between the ages of 36 to 43 years, 74% to 87% of whom were women.
The primary outcome of the analysis was the odds ratio for freedom from pain (“pain freedom”) at 2 hours post-dose. The researchers found that triptans were associated with higher pain freedom at 2 hours compared with lasmiditan, rimegepant, and ubrogepant, .
Pain relief and adverse events were also measured 2 hours post-dose. In this measure, triptans were also associated with higher general pain relief at 2 hours relative to lasmiditan, rimegepant, and ubrogepant.
Taken together, most of the studied acute migraine treatments gave participants pain relief 2 hours post-dose in comparison to placebo. Of all studied treatments, lasmiditan was most likely to cause adverse events, while rizatriptan, sumatriptan, and zolmitriptan were associated with an increased risk of adverse events over gepants.
Do ditans and gepants measure up clinically?
“Clinically, ditans and gepants are not any more effective than triptans, with high numbers of patients stopping them for lack of benefit or adverse events,” said Freitag. “Tolerability is good with gepants since they do not seem to have an increase in [likelihood of adverse events] with migraine duration or severity, which is not true of triptans and reflected in this analysis.”
Ditans and gepants are better for people with cardiovascular and cerebrovascular diseases, but they are not completely known to be safe, said Freitag.
“Cardiovascular risks of triptans and dihydroergotamine are one-off occurrences and likely related to unknown genetic variations that lead to increased vascular reactivity at the 5-HT1B receptor,” said Freitag. “Since it’s a vasospastic issue that produces cardiovascular issues, people in their 40s and 50s who have calcified vascular lesions or heavily plaqued [and therefore] can’t vasospasm [are the concern].”
Big pharma distractors?
While pharma companies promote these new under-patent drugs as superior to triptans, “none dared to do a comparator trial to older agents, and if they do in phase 4, they will be stacked so they win,” said Freitag. Pharma-sponsored copay programs also allow them to have these at little or no out-of-pocket cost to patients, Freitag noted.
“The presumed but unproven advantage is that the new drugs [do not cause] medication-overuse headaches, which may take time to become apparent if it exists,” he said. Triptan medication overuse is also not likely, since according to Freitag frequency and duration of use would have to exceed insurance-approved quantity limits and occur for at least a year, respectively.
So while ditans and gepants are still new to the landscape of acute migraine treatment and require further study to determine efficacy and tolerability, Yang and colleagues’ review and meta-analysis of these newer pharmacotherapies shows that it may be beneficial to consider their use especially in patients who are at risk for cardiovascular-related adverse events. ■