Aimovig: An Approach for Migraine Prevention?

Aimovig is a monoclonal antibody that prevents migraines

injection
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There are two kinds of migraine therapy: abortive or preventive. Abortive treatments are used during a migraine attack, with the aim of stopping it. Triptans and NSAIDs like acetaminophen and ibuprofen (Advil) are abortive treatments.

Preventive treatments attempt to reduce the frequency and severity of migraine headaches. These medications are broadly categorized as oral migraine-preventive medications (OMPMs) and include antidepressants, anticonvulsants, and beta-blockers.

In a November 2017 article published in the New England Journal of Medicine, Goadsby and co-authors examined the ability of Aimovigto (erenumab) to prevent migraine attacks. Unlike current OMPMs, Aimovig is a biologic product—a monoclonal antibody. Specifically, Aimovig prevents migraines by blocking the calcitonin gene-related peptide (CGRP) receptor, which is linked to migraine activation.

Who Was Included in Aimovig Trials?

During Phase 2 and Phase 3 clinical trials, Aimovig has been tested on patients with both episodic and chronic migraines.

Episodic migraines are defined as fewer than 15 migraine or headache days per month, either with or without aura. Chronic migraines are defined as at least 15 headache days per month. At least eight of these fifteen days are migraine days either with or without aura.

Episodic migraines are more common—about 90 percent of people with migraines have them. Between 5 percent and 8 percent of people with migraines have chronic migraines.

About the Trial

In a November 2017 article published in the New England Journal of Medicine, Goadsby and co-authors examined the ability of Aimovig to prevent migraine attacks.

In this study, there were 995 adult participants divided into two experimental groups and a control group. The control group received a placebo injection, and the experimental groups received either a 70 mg or a 140 mg subcutaneous injection of Aimovig, administered as six doses spaced four weeks apart.

According to the authors, both dosages “reduced migraine frequency, the effects of migraines on daily activities, and the use of acute migraine–specific medication over a period of 6 months.”

At baseline, the number of migraine days experienced each month by participants in the study was 8.3 days. Between months four and six of treatment, the number of migraine days decreased by 3.2 and 3.7 in the 70-mg Aimovig and 140-mg Aimovig groups, respectively.

Between the start of the study and four to six months of treatment, in the 70-mg group, 43.3 percent of patients experienced at least a 50 percent reduction in the number of migraine days experienced each month.

Between the start of the study and four to six months of treatment, in the 140-mg group, 50 percent of patients experienced at least a 50 percent reduction in the number of migraine days experienced each month.

Between the start of the study and four to six months of treatment, in those receiving placebo, 26.6 percent experienced at least a 50 percent reduction in the number of migraine days experienced each month.

The number of days in which patients had to use specific medications to treat acute migraines was decreased by 1.1 days in the 70-mg group and 1.6 days in the 140-mg group as compared with 0.2 days in the placebo group.

Impairment of daily activities makes migraines debilitating. Using a questionnaire, the researchers assessed improvements in the performance of everyday activities. They found significant improvements in those receiving Aimovig.

Adverse Effects and Limitations

Although adverse effects of Aimovig were reported by the majority of participants, these adverse events were for the most part no different from those receiving placebo. Notably, more people receiving 70 mg of Aimovig reported pain at the injection site than did those in the control group.

Examples of more common adverse events included cold, upper respiratory tract infection, and sinusitis.

One limitation of the study was that the researchers didn’t include patients who experienced no therapeutic benefit from two or more classes of OMPMs.

However, researchers did include patients who discontinued OMPMs due to insufficient efficacy, lack of a sustained response, or unpleasant adverse effects. In fact, 38.7 percent of patients in the sample had previously experienced no benefit from OMPMs.

Furthermore, according to Goadsby and co-authors:

"Efficacy was similarly demonstrated in a phase 2 trial of erenumab involving patients with chronic migraine, in which 68 percent of patients had previously discontinued migraine-preventive medication because of a lack of efficacy or unacceptable side effects."

When combined with results from other Phase 2 and Phase 3 clinical trials examining the use of Aimovig in those with chronic and episodic migraine, it appears that Aimovig can help prevent episodic migraines.

More research needs to be done to elucidate the long-term safety of Aimovig, as well as how long its effects last.

How Aimovig Stacks Up to OMPMs

One big difference between Aimovig and OMPMs is that Aimovig specifically targets specific pathophysiological processes that play a role in migraine.

Not enough research has been done to compare the effects of Aimovig with other medications used to prevent migraine headaches. Moreover, there isn’t a lot of research examining the efficacy of OMPMs themselves.

According to the American Academy of Neurology:

"Evidence is also unavailable for making broad-range comparisons among multiple agents within a single class; such evidence would provide a more comprehensive understanding of relative efficacy and tolerability profiles across a broader range of therapeutic agents. Studies are needed that specifically evaluate when preventive therapy is warranted and how medications should be titrated."

Only a limited number of studies have examined the efficacy of OMPMs. According to the AAN, there is either strong or moderate evidence supporting the efficacy of the following preventive treatments:

  • Divalproex sodium, sodium valproate, and topiramate (antiepileptic drugs)
  • Metoprolol, propranolol, timolol, atenolol, and nadolol (beta-blockers)
  • Amitriptyline and venlafaxine (antidepressants)

Furthermore, gabapentin, lamotrigine, clomipramine, and fluoxetine, which are prescribed for migraine prevention, are probably not effective at preventing migraines.

Of note, treatment with anti-epileptic drugs requires careful follow-up for pancreatitis, liver failure, and teratogenic effects such as birth defects. Furthermore, divalproex sodium can cause weight gain. So far, it appears that Aimovig doesn’t pose such adverse effects.

One thing that we do know about OMPMs is that adherence is low. In other words, lots of people who take these medications stop taking them.

In a retrospective study published in Cephalagia in 2015, Hepp and colleagues examined the efficacy of 14 different types of OMPMs for the treatment of chronic migraines. Among 8688 patients, adherence rates at six months ranged between 26 percent and 29 percent. At 12 months, adherence rates dropped to between 17 percent and 20 percent.

According to the authors:

"Although the reasons for nonadherence are not captured in claims data, previously published studies suggest that low adherence may be attributed to a number of factors, including side effects and/or lack of efficacy of the OMPM. Furthermore, treatment guidelines by the AAN also point out that only a handful of the OMPMs available actually have good clinical evidence of their efficacy in preventing migraine headaches."

Interestingly, the researchers found that of the 14 OMPMs tested, amitriptyline, nortriptyline, gabapentin, and divalproex had significantly lower rates of adherence when compared with topiramate.

Neurostimulation

Here is a fundamental issue with migraines: We don’t really understand how they work. Without a clear understanding of the mechanisms of this illness, it’s difficult to create novel abortive and preventive treatments that target specific pathways.

Consider the following passage from a 2013 review article titled “Migraine: a brain state”:

"Hypotheses of migraine pathogenesis have typically focused on a primary region of initiation such as spreading depression in the cortex or a ‘migraine generator’ in the brainstem. But the temporal progression of a migraine attack indicates simultaneous changes in the function of multiple brain regions, and it is not clear that there is a single anatomical region wherein migraine begins in all patients."

Like Aimovig, Cefaly aims to directly disrupt the pathogenesis of migraine by targeting mechanisms. Unlike Aimovig, which is given as an injection, Cefaly is a neurostimulation device placed over the forehead. It stimulates the trigeminal nerve, which is thought to play a big role in migraines.

Cefaly was recently approved by the FDA not only as a preventive intervention but also an acute treatment, too. It comes in three models: Cefaly Acute, Cefaly Prevent, and Cefaly Dual. (Cefaly Dual has modes for both the acute and the preventive treatment of migraines.)

According to its makers, Cefaly Prevent administers a low-intensity current which can be used daily to prevent migraine attacks.

In clinical trials, which occurred between 2009 and 2012, those receiving Cefaly treatment for the prevention of migraines experienced a significant decline in both migraine and headache days after three months of use.  

More specifically, patients who received Cefaly treatment experienced 29.7 percent fewer migraine days and 32.3 percent fewer headache days. Furthermore, 38.2 percent of patients receiving Cefaly experienced at least a 50 percent reduction in monthly migraine days.

In addition to experiencing fewer migraine and headache days, those using Cefaly also required less anti-migraine medication (“rescue medications”). Of note, there were no serious adverse effects in those receiving Cefaly treatment.

During a post-marketing study conducted by Cefaly, 53 percent of patients who received the device were happy with it. Only 4 percent of users reported dissatisfaction and reported minor adverse effects, such as sleepiness, headache, or tingling caused by the device. As with the clinical trials, there were no serious adverse effects secondary to Cefaly treatment. 

A Word From Verywell

Although we don’t fully understand how migraines work, new interventions such as the biologic product Aimovig, as well as the neurostimulation device Cefaly, aim to disrupt the mechanisms of this illness. Aimovig has yet to be approved by the FDA, but Cefaly is available. If interested in these or other preventive treatments, discuss them with your neurologist.

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