For Patients With Migraine, Are CGRP Inhibitors Worth the Cost?


A recent review of the ICER report on calcitonin gene-related peptide inhibitor monoclonal antibodies has suggested that due to their cost and comparative benefit to available treatments, they should be reserved as second-line treatments.

Dr Elizabeth Loder

Elizabeth Loder, MD, MPH

In part due to their cost, calcitonin gene-related peptide (CGRP) inhibitor monoclonal antibodies should be reserved for the patients with incapacitating high-frequency episodic migraine or chronic migraine who have not benefited from or cannot tolerate first-line preventive treatments, according to a recent review.1

The review, an examination of the Institute for Clinical and Economic Review (ICER) 2018 evidence report on migraine treatments was an assessment of the first 2 CGRP inhibitors to be approved, erenumab (Aimovig, Amgen/Novartis) and fremanezumab (Ajovy, Teva).2 It used network meta-analysis (NMA) to compare the 2 treatments to with placebo and other commonly used preventives. It estimated that change from baseline ranged from 3.5 fewer migraine days per month with 70-mg erenumab to 4.1 fewer migraine days per month with 140-mg erenumab, compared to 4 fewer migraine days per month for topiramate at 100 mg/d, and propranolol at 160 mg/d.

Coauthors Elizabeth Loder, MD, MPH, and William Renthal, MD, PhD, both from the Division of Headache at Harvard Medical School and Brigham and Women’s Hospital, wrote that although fremanezumab and erenumab improve the outcomes of patients with chronic and episodic migraine “relative to no treatment,” their outcomes and those of the currently available therapies are relatively similar.

Some experts have expressed some disagreement with the focus on the CGRP inhibitors’ therapeutic gains—a point in the ICER analysis. David Dodick, MD, the director of the headache and concussion programs at Mayo Clinic in Phoenix, noted in a NeurologyLive Peer Exchange program that therapeutic gain is “meaningless in clinical practice,” and that the focus should be on magnitude of response.3

“Inevitably, what happens is you not only mirror that magnitude of response, but you’re better than it,” he explained. “The reason is you’ve taken placebo off the table. So, the patient’s not wondering, ‘Do I have a 50-50 chance of getting a placebo.’ And number 2, you’re doing more things for the patient. You’re not just writing a prescription, right? I think actually we do better in clinical practice than the results we get in clinical trials. My advice to clinicians is to use the magnitude of the response when you determine clinical benefit and not look at 1.8 or 2.2 or 2.4 days and the difference.”

Loder and Renthal wrote that a point of contention with the new treatments is their unknown cost. Notably, they acknowledged that “the cost of the CGRP [monoclonal antibodies] is likely to exacerbate existing treatment inequities because people of low socioeconomic status are more likely to experience migraine but have less access to treatment.”

Loder and Renthal pointed to an editorial written by Rebecca Burch, MD, and Melissa Rayhill, MD, in which the authors call attention to the ICER report’s estimation that the cost of each migraine-free day with erenumab or fremanezumab is between $130 and $340, in comparison with no treatment or treatment with onabotulinumtoxin A (Botox).4

“At the current price, it estimates that only 20% of patients who do not respond to one preventive treatment could be treated with erenumab without exceeding the cost burden that society is willing to bear,” Burch and Rayhill wrote. Both pairs of authors remarked that in order for the entire eligible patient population to gain access to the treatments at “acceptable societal costs,” a 75% reduction in price (roughly $2200 per year) would need to be achieved.

The list price of erenumab, which is similar to the other 2 approved agents, fremanezumab and galcanezumab (which was not included in the ICER report), is $6900 per year. Its manufacturers, Amgen and Novartis, do offer an access card program, called Aimovig Ally, for patients which offers a $5 copay per month feature or a 12-dose, no-cost feature for those whose insurance does not cover the cost of treatment.

The availability of the access card is dependent on health plan coverage and the requirement of prior authorizations, with the potential to “help reduce prescription costs to no more than $5 per month up to a $2,700 annual cap.” For those whose insurance does not cover erenumab, the manufacturing duo also offers a Bridge to Commercial Coverage plan, which provides “up to 12 doses to patient while insurance coverage is pursued for up to 24 months from enrollment, whichever occurs first.”5

Loder and Renthal wrote that the ICER economic model faced the limitation of focusing on CGRP inhibitors’ benefits in comparison with placebo, calling it an inappropriate comparator due to the availability of other preventive agents with established efficacy data. “Compared with commonly used doses of propranolol or topiramate, the antibodies’ cost per [quality-adjusted life-year] exceeds reasonable thresholds, and the overall budget impact is likely to be substantial,” they explained.


1. Loder E, Renthal W. Calcitonin gene-related peptide monoclonal antibody treatments for migraine. JAMA Intern Med. Published online January 14, 2019. Accessed January 18, 2019.

2. ICER. Calcitonin gene-related peptide (CGRP) inhibitors as preventative treatments for patients with episodic or chronic migraine: effectiveness and value: final evidence report. Published July 3, 2018. Accessed January 18, 2019.

3. Tepper S, Silberstein S, Dodick D, Gadsby P, Ailani J. Chronic migraine: new paradigms in management. Unprecedented efficacy of CGRP inhibitors for migraine. NeurologyLive website. Published January 8, 2019. Accessed January 18, 2019.

4. Burch R, Rayhiill M. New preventive treatments for migraine. BMJ. 2018;361:k2507. doi: 10.1136/bmj.k2507

5. Your access to Aimovig. Aimovig website. Accessed January 18, 2019.

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