The anti-calcitonin gene-related peptide (CGRP) monoclonal antibody erenumab (Aimovig) helps patients with chronic migraine convert to an episodic pattern soon after treatment initiation, new research suggests.

In an open-label study, 71% of patients with chronic migraine treated for 1 year converted to episodic migraine.

“Erenumab is related to a remarkably high percentage of pattern reversal and is even associated with improvement in clinical headache features,” investigator Gloria Vaghi, MD, IRCCS Mondino Foundation, University of Pavia, Italy, told meeting attendees.

The effect was observed after the first treatment and was maintained over the  long-term in a cohort of difficult-to-treat patients. In addition, this pattern reversal occurred at a higher rate than had been shown in previous clinical trials, Vaghi said.

The findings were presented at the virtual World Congress of Neurology (WCN) 2021.

Direct Mechanism

Chronic migraine is defined as 15 or more headache days per month, with migraine features on 8 or more of those days, for at least 3 months. These patients also often experience medication overuse headache.

Monoclonal antibodies directed against CGRP or its receptor have been approved over the past few years. CGRP is released by the trigeminal nerve, and monoclonal antibodies either bind to CGRP within the synapse or bind directly to its receptors to block CGRP from activating them.

Of the four monoclonals approved by the US Food and Drug Administration, erenumab is the only one that binds to the receptor, the investigators note.

The current study included 82 participants (72% women; mean age, 50 years) with headache duration of 14 ±7 years and a mean duration of chronicity of 13 ±11 years.

The majority (90%) also had medication overuse headache. All had failure of three or more previous preventive treatments, including 73% who had tried onabotulinum toxin A. About one third had a drug washout before starting erenumab, and half were taking ongoing prophylaxis. Psychiatric comorbidities of depression and anxiety were also common (59%).

After an initial dose of 70 mg of erenumab, participants received the drug every 28 days for 1 year. The drug was increased up to 140 mg at the clinician’s discretion. Forty-four of the patients were on the higher dose by month 3.

Thirteen patients discontinued erenumab for either for lack of efficacy (n = 11) or for personal reasons despite good efficacy (n = 2) after a mean of 7.3 months.

Of the remaining 69 patients, 65 were receiving the higher dose by the end of study. The current analysis was conducted based on the 69 study completers.

Patients kept diaries to document headache frequency and acute medication use. Every 3 months, they also filled out Migraine Disability Assessment (MIDAS) questionnaires, the Headache Impact Test-6 (HIT-6), the Allodynia Symptom Checklist-12 (ASC-12), and the Hospital Anxiety and Depression scales (HADS-A and HADS-D).

Early, Sustained Pattern Reversal

Results showed patients achieved the primary outcome of pattern reversal from chronic to episodic migraine at all time-points of 1, 3, 6, 9, 12, and 13 months compared with baseline (P < .01 for all treatment timepoints).

Table. Patients with a pattern reversal from chronic to episodic migraine.

“As we can see during the period of observation, there is a growing percentage of the responders,” Vaghi reported. “It is worth noting that our data show a higher percentage of a response compared to a previous clinical trial.”

After the first monthly dose, 10.2% of the patients experienced a 75% or greater reduction in monthly migraine days. By end of trial at 13 months, the figure had increased to 36.2% of patients.

Roughly a quarter of patients (23.2%) had a 50% to 74% reduction in migraine days after 1 month — and this increased to 38.4% at 13 months.

Combining the 13-month data, three quarters (74.6%) of the participants were experiencing a 50% or greater reduction in monthly migraine days at that timepoint.

Concomitant with the reduction in number of migraine days was a precipitous drop in medication use. Monthly acute medication doses dropped from 31.9 doses at baseline to 12.3 doses at month 1 and to 8.1 doses at month 13.

Similarly, days of drug intake fell from 20.3 days at baseline to 9 days at month 1 and to 6.8 days at month 13 (P < .001 at all study timepoints vs baseline for monthly doses and for days of medication use).

Patients also experienced reduced disability, as measured on the MIDAS and HIT-6 scales (P < .001 at months 3, 6, 9, and 12/13 vs baseline for both measures), and they showed reductions in allodynia at months 6, 9, and 12 vs baseline (P < .001).

There were small, but statistically significant drops in anxiety at months 9 and 12/13 on the HADS-A self-evaluation scales, but even at baseline the score of 6.1 was considered within the normal range (≤ 7). There was also a small but significant reduction in depression at the same time points.

“These are all valuable findings, especially when considering the social burden of migraines,” Vaghi said.

Patients’ satisfaction with treatment was moderately good at 6.6 out of 10 on a visual analog scale at month 1, with a rise to 7.1 at month 12.

About 50% of participants reported any adverse event (AE) throughout the trial. The most commonly reported AEs were fatigue (in 10% – 19%), constipation (9.6% – 16.4%), or cutaneous reactions (4.1% – 6.8%).

“No patients interrupted treatment because of adverse reactions,” Vaghi reported.

Promising but Preliminary

Commenting on the findings for Medscape Medical News, Kiran Rajneesh, MBBS, a neurologist and pain medicine specialist at The Ohio State University Wexner Medical Center in Columbus, noted that Vaghi presented a very promising preliminary study. “But the key there is the preliminary part,” he said.

“It’s a single center study, but very promising for patients with chronic migraine headaches, especially the ones that are refractory,” said Rajneesh, who was not involved with the research.

Because women experience migraines more than men, he said the study was positive in showing good responses overall in a cohort consisting mainly of women.

Rajneesh expressed concern, however, about not knowing the socioeconomic make-up of the study cohort and their access to medications “because these antibodies are fairly expensive.”

He noted that in the United States, access for a patient with chronic pain is a big challenge — whether that access refers to insurance to pay for medications or even [access] to a heated pool for water therapy.

“I’m not well versed with how the European healthcare system works and who can [get] medications vs us,” he said. “And that is a concern, as we’re seeing it unfold over our society that everybody should have the equal right to feel healthy and to feel pain free.”

Vaghi and Rajneesh have disclosed no relevant financial relationships.

XXV World Congress of Neurology (WCN 2021). Presented October 3-7, 2021.

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