Post Hoc Analysis Finds Erenumab Enables Reversion From Chronic to Episodic Migraine

The analysis, published in Cephalalgia, found that more than 50% of patients exhibited reversion from chronic migraine to episodic migraine after week 12 of the double-blind treatment phase.

Results from a post hoc analysis of a double-blind trial and open-label extension showed that monthly treatment with erenumab, a calcitonin gene-related peptide (CGRP) inhibitor, reduced migraine frequency among chronic migraineurs. The analysis, published in Cephalalgia, found that more than 50% of patients exhibited reversion from chronic migraine (CM) to episodic migraine (EM) after week 12 of the double-blind treatment phase (DBTP).

Erenumab, which was approved by the FDA in 2018, is administered monthly via self-injection of a 70-mg or 140-mg dose. The treatment blocks the CGRP receptor, which is believed to play a crucial role in migraine.

CM is defined by the occurrence of headache on 15 or more days per month for more than 3 months, with at least 8 days/month linked to migraine, whereas EM is the complement of CM, researchers explained. If monthly headache frequency decreases to less than 45 days for at least 12 weeks, investigators considered it a reversion from CM to EM.

Previous studies have found the annual rate of transitioning from EM to CM is roughly 2.5% in population-based studies and around 14% in clinic-based studies.

Researchers performed a post hoc analysis of a 12-week placebo-controlled trial of patients with CM and a subsequent 52-week, open-label extension to better assess reversion rates from CM to EM. However, authors cautioned that “the state of reversion that is associated with treatment is provisional, as there conceivably might be movement back to CM.”

Once patients completed the 12-week DBTP, they were eligible for entry into the 52-week open label treatment phase (OLTP) if they provided informed consent and were deemed appropriate for continued treatment by the investigator.

During the trial all participants were randomized 3:2:2 to receive monthly placebo, erenumab 70 mg, or erenumab 140 mg. Information on headache duration, intensity and symptoms was collected daily during the 4 weeks before baseline, the 12-week DBTP, and over the first 12 weeks and weeks 21 to 24, 37 to 40, and 49 to 52 of the OLTP. Patients used an electronic diary to enter headache information and an algorithm was used to determine which days qualified as migraine vs headache.

In addition to reversion to EM over 12 weeks of treatment, monthly reversion, delayed reversion, delayed long-term reversion, and long-term reversion to EM were also assessed.

Of the 637 patients who completed the DBTP, 609 patients entered the 52-week OLTP. During the extension, “549 patients started on erenumab 70 mg, and 60 started on erenumab 140 mg. Of the patients who started on erenumab 70 mg, 199 switched to erenumab 140 mg at the week 28 visit or earlier. During the OLTP, 139 patients (22.8%) discontinued treatment,” the researchers wrote. The 2 most common reasons for discontinuation were patient request and lack of efficacy.

Analyses revealed:

  • In the double-blind treatment phase, 53.1% (95% CI, 47.8%-58.3%) of 358 erenumab-treated completers had reversion to EM.
  • In this phase, monthly reversion rates to EM were typically higher among patients receiving 140 mg vs 70 mg of erenumab.
  • Among 181 completers (receiving erenumab for 64 weeks), 98 (54.1% [95% CI, 46.6%-61.6%]) had reversion to EM during the double-blind treatment phase.
  • Of the 181 completers 96.9% (95% CI, 91.3%-99.4%) had persistent reversion to EM (over 24 weeks), 96.8% (95% CI, 91.1%-99.3%) of whom had long-term persistent reversion to EM (over 64 weeks).
  • Delayed reversion to EM occurred in 36 of 83 (43.4% [95% CI, 32.5%-54.7%]) patients; of these, 77.8% (95% CI, 60.9%-89.9%) persisted in reversion through week 64.

Although the number of monthly acute migraine-specific medication days at baseline was similar in EM reverters vs nonreverters, those who reverted from CM to EM over the DBTP exhibited fewer monthly headache days and monthly migraine days (MMDs) at baseline. These patients also had fewer prior failures of migraine preventive treatment compared with those who remained in CM.

Investigators found that “patients achieving persistent EM reversion over 24 weeks had a mean (SD) reduction in MMDs from parent study baseline of 10.3 (4.6) days, and those achieving long-term persistent EM reversion over 64 weeks had a mean (SD) reduction in MMDs from parent study baseline of 11.4 (4.7) days, indicating that the reversion to EM was associated with a substantial reduction in monthly migraine days.”

Because participants of the OLTP were not randomized to 70 mg to 140 mg and the extension did not have a placebo-control group, bias may have been introduced, marking a limitation to the study. Results may also not be generalizable to the wider migraine population as patients with comorbidities including fibromyalgia were not eligible for enrollment in the double-blind trial and were thus not included in the OLTP.

“Overall, approximately two-thirds of patients with CM receiving erenumab are likely to attain reversion to EM and persist in this state after 64 weeks of treatment,” researchers concluded.


Lipton RB, Tepper SJ, Silberstein SD, et al. Reversion from chronic migraine to episodic migraine following treatment with erenumab: results of a post-hoc analysis of a randomized, 12-week, double-blind study and a 52-week, open-label extension. Cephalalgia. Published online December 3, 2020. doi:10.1177/0333102420973994