Intended for healthcare professionals


New preventive treatments for migraine

BMJ 2018; 361 doi: (Published 13 June 2018) Cite this as: BMJ 2018;361:k2507
  1. Rebecca Burch, assistant professor of neurology1,
  2. Melissa Rayhill, assistant professor of neurology2
  1. 1Harvard Medical School Boston, Massachusetts, USA
  2. 2Jacobs School of Medicine and Biomedical Sciences State University of New York, Buffalo, New York, USA
  3. Correspondence to: R Burch rburch{at}

High prices put promising monoclonal antibodies out of reach for many patients

What is a day without migraine worth? Drug companies, payers, and patients are wrestling with this question as new treatments for migraine are developed and brought to market. Monoclonal antibodies to calcitonin gene related peptide or its receptor (CGRP mAbs) are a novel class of preventive treatment aimed at reducing the frequency of episodic migraine, chronic migraine, or cluster headache.

CGRP is a widely distributed vasodilatory neuropeptide that is involved in migraine pathophysiology. Four antibodies to CGRP or its receptor have been developed. Erenumab was approved by the US Food and Drug Administration on 17 May 2018, and a marketing application is under review by the European Medicines Agency. Galcanezumb and fremanezumab are under FDA review; eptinezumab’s licensing application has yet to be submitted to the FDA.

This new class of drugs is a welcome development for the estimated one billion people worldwide who have this chronic, disabling illness.1 Patients with infrequent migraine often manage headaches with symptom relieving drugs such as triptans. When headaches are frequent, additional preventive drugs are needed. Existing preventive treatments are not effective for everyone, and some are poorly tolerated. Although trials of CGRP mAbs reported a modest reduction in days with migraine per month compared with placebo, the treatments had few adverse effects.2345

How much is modest efficacy and improved tolerability worth, especially when we lack information on long term safety? A draft report from the US Institute for Clinical and Economic Review (ICER) tries to answer this question, using a premarket estimated price of $8500 (£6300; $7200) a year for antibody treatment.6 An ICER network meta-analysis compared efficacy, safety, and cost effectiveness of erenumab and fremenezumab with existing preventive treatments (onabotulinum toxin A, topiramate, propranolol, and amitriptyline). Efficacy compared with placebo was similar for all treatments. The reduction in the number of days with migraine a month ranged from 1.3 to 2.4 in people with chronic migraine (headaches 15 or more days a month) and 0.9 to 2 days in those with episodic migraine.6

The ICER report rates the net benefit of erenumab and fremanezumab as “comparable or better” than comparators for patients with chronic migraine who have not responded to one other preventive treatment. The evidence on erenumab and fremanezumab for episodic migraine was judged largely inconclusive because long term efficacy and safety data weren’t available, with most trials lasting only 12 weeks. Since CGRP is a systemic vasodilator, rare but serious adverse events may become apparent only in post-marketing surveillance.

The report also notes that trials of these agents excluded participants who had already tried more than two other preventive therapies. This could limit generalisability to clinical practice. Clinical trials suggest that CGRP antibodies may be associated with fewer side effects than olderpreventive treatments. Post-marketing surveillance required by the FDA should provide more information.7

The manufacturer’s listed price for erenumab is $6900 a year. Although this is below the predicted price, it is still around $150 000 per quality adjusted life year (QALY)—a threshold that strains the accepted upper limits of cost effectiveness in most countries.68 The ICER estimates that each migraine-free day attributed to erenumab or fremanezumab costs between $130 and $340, relative to no treatment or treatment with onabotulinumtoxin A.

At first glance, this may seem reasonable for a highly disabling disease, but the budget busting implications of this pricing strategy are shown by ICER estimates of patient access to these treatments. 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. A roughly 75% reduction in price of erenumab or fremenezumab, to $50 000 per QALY ($2200 a year), would be needed to achieve full coverage of the eligible population at acceptable societal costs.

Access to erenumab will therefore be limited. If subsequent CGRP antibodies are priced similarly, this entire class of treatments may be out of reach for many patients. In the US, migraine disproportionately affects people of low socioeconomic status and those who are under-insured.9 Such patients were also underrepresented in CGRP mAB clinical trials, which enrolled predominantly white women. Unfortunately, the highly disabled migraine patients who need these treatments most would be least likely to have access.

Patients in the US are already struggling to afford essential headache treatments. Prices for previously inexpensive, well established migraine treatments have skyrocketed in recent years.1011 Clinicians and patient advocacy groups must oppose inflated prices for new and existing drugs that effectively lead to rationing of treatment according to socioeconomic status.

If we unquestioningly accept high prices and the industry arguments to justify them, we are complicit in pricing patients out of treatment. Poorly treated migraine is associated with high costs to society, and limiting access may prove short sighted. The price of these agents must fall – both to reflect their modest efficacy, and to allow more equitable access to a treatment option that might succeed where others have failed. Otherwise, the price of progress may be simply too high.


  • Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

  • Provenance and peer review: Commissioned; not externally peer reviewed.


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