ICER Releases Final Evidence Report on Acute Treatments for Migraine

The Institute for Clinical and Economic Review (ICER) released its final evidence report on acute treatments of migraine on February 25. The Institute’s last report on migraine treatment was released in 2018.

The report includes assessments of 2 therapeutic drug classes aimed to mitigate or prevent migraine among patients: calcitonin gene-related peptide (CGRP) antagonists and 5-hydroxytryptamine (5-HT 1f) agonists. Administrating CGRP has been shown to delay migraine-like attacks while monoclonal antibodies targeting the CGRP receptor are used in migraine prophylaxis.

Although some migraineurs respond well to existing therapies, medication may wear off during acute episodes and responses may decrease over time with episodic use. This leaves open a possibility for therapies that provide long-term control and relief of acute attacks. Authors included insights from patients and patient support groups to better formulate recommendations and assess effective treatment options.

Trials involving 2 oral CGRP receptor agonists, ubrogepant and rimegepant, along with lasmiditan, a selective 5-HT 1f agonist, were considered for clinical effectiveness and safety. Ten randomized controlled trials were included on the 3 treatments, and all but 1 phase 2 trial of rimegepant were placebo controlled. Treatments were compared with control groups or use of triptans (eletriptan and sumatriptan), the most commonly used migraine-specific medication.

The ICER meta-analysis found that “overall, a greater proportion of patients achieved freedom from pain and pain relief at 2 hours post dose with the interventions compared to placebo.” The 2-hour mark was evaluated upon recommendation from migraineurs.

Researchers defined sustained pain freedom as “individuals who were pain free at 2 hours and maintained pain freedom with no use of rescue medication or relapse within 24 or 48 hours…after the initial treatment.” Results showed a greater proportion of patients treated with interventions achieved sustained pain freedom at 24 hours compared with those who received placebos. Differences in treatment method were not statistically significant.

Bothersome symptoms such as phonophobia, photophobia, or nausea were also measured. The meta-analysis found patients who took lasmiditan, rimegepant, or ubrogepant all had higher odds of relief from these symptoms 2 hours after receiving doses compared with controls. Again, there was no statistically significant difference among interventions.

Adverse events were reported as mild or moderate in intensity among trial participants. However, researchers note “in the open-label extension study of lasmiditan, 12.8% of patients discontinued the trial due to adverse events, and dizziness was reported to be the most common adverse event leading to discontinuation (2.7% of patients in the 100 mg group, and 4.3% of patients in 200 mg group).”

The majority of data collected on these treatments measured relief of a single migraine attack, meaning use outcomes for repeated attacks is largely unknown. “Important long-term outcomes such as the effect of these medications on potentially decreasing the frequency of migraine attacks, the occurrence of medication overuse headaches, and the need for other therapies such as opioids and barbiturates are currently not known,” authors said.

In addition, to determine long-term cost effectiveness researchers developed a de novo semi-Markov model and compared the 3 interventions to each other and 3 comparators. The factors were tested across 2 populations, those who can take triptans and those for whom triptans are not effective or tolerated.

For patients who can take triptans, researchers found that sumatriptan and eletriptan are more effective than the interventions and less expensive. For those who cannot take triptans, researchers determined “rimegepant (assuming similar pricing to ubrogepant) and ubrogepant are cost effective at commonly used thresholds.” However, lasmiditan exceeded the per quality-adjusted life-year (QALY) gained threshold ($150,000) in the same population.

Due to differing clinical trial designs, some price estimates are uncertain. “More evidence is required to obtain better precision in cost-effectiveness estimates for lasmiditan, rimegepant, and ubrogepant when compared with usual care,” authors said.

Listed in the report are additional benefits and contextual considerations migraineurs can take into account when assessing the new agents.

Value Our Health, a patient advocacy group, responded to the report and claimed ICER’s findings contained “alarming flaws.”

Specifically, the group contests how ICER utilized the QALY metric, which they deem discriminatory due to the fact it is “not an accurate reflection of how migraine patients view the value of their own lives.” Value Our Health also claims ICER disserved female migraine patients because the final results of its analysis were not stratified by sex. Additionally, the group says the report “makes oversimplified assumptions regarding mortality effects of migraines” and “fails to incorporate outcomes that matter to patients.”

In a joint statement, the Coalition for Headache and Migraine Patients (CHAMP) and Headache & Migraine Policy Forum (HMPF) called the ICER report a “partial win for people living with migraine.” Although the organizations laud the institute for including diverse stakeholder insights, “we continue to have concerns that the ICER approach under-counts the real economic costs of migraine disease and under-values the benefits of these new medicines.” In addition, the 2 organizations call on ICER to rerun the analysis on the 3 acute treatments using a new framework to ensure greater inclusion of societal factors.