Erenumab Dosage for Migraine Prevention

An Evidence-Based Narrative Review With Recommendations

Stewart J. Tepper MD; Huma U. Sheikh MD; Carrie O. Dougherty MD; Stephanie J. Nahas MD MSEd; Paul K. Winner DO; Ananda Krishna Karanam PhD; Andrew M. Blumenfeld MD; Ahmad Abdrabboh PharmD MPH; Soeren Rasmussen MD; Jamie L. Weiss PhD; Jessica Ailani MD

Disclosures

Headache. 2022;62(4):420-435. 

In This Article

Discussion

Herein we have reviewed the totality of the available evidence for both doses of erenumab across clinical and real-world studies and across diverse endpoints ranging from MMDs to PROs. We have not conducted a meta-analysis due to apparent clinical and methodological heterogeneities across the identified studies in terms of different populations, classification (CM and EM), disease severity, study design, secondary outcomes evaluated, and time points examined for outcome measures. Further, the studies identified in this review were not designed to compare the two doses of erenumab. We therefore precluded a meta-analysis and chose a narrative synthesis of the evidence for descriptive purposes.

Overall, our detailed review of efficacy parameters regarding the two erenumab doses indicates that, in general, administration of erenumab 140 mg provides numerical benefits compared with erenumab 70 mg.[10,11] The incidence of AEs for erenumab 70 and 140 mg was similar between the subgroups. As per AHS recommendations, CGRP-targeted mAbs should be used for at least 3 months to allow for temporal response patterns to be assessed.[4] While some experience onset of efficacy within the first week of treatment,[27] a proportion may respond later during subsequent months.[4,30,31]

Limited real-world evidence retrieved in our search suggests that initiating treatment with erenumab 70 mg is generally the case in current clinical practice. However, the evidence retrieved also suggests there may be merit in starting with or switching to the higher dosage of erenumab 140 mg. Indeed, evidence from the STRIVE ATP[24] indicates that a therapeutic advantage can be achieved by switching from erenumab 70 to 140 mg. The data suggest that erenumab 140 mg may indeed be the more optimal dose when aiming for a dose–response relationship, balancing efficacy with AEs.

Erenumab is indicated for the preventive treatment of migraine in adults. The US list price of once-monthly erenumab is the same for both 70 and 140 mg doses. Most patients do not pay the list price, with the actual cost to them varying based on their insurance coverage.[35] While erenumab 70 mg is the recommended starting dosage in the prescribing information, the choice between erenumab 70 and 140 mg could also be guided based on factors which signify difficult-to-treat disease. These include patients in whom prior preventive treatments were unsuccessful[13,14] and those with acute medication overuse.[15] Our assessment of the evidence indicates that erenumab 140 mg has a numerical benefit across most outcomes in individuals with difficult-to-treat disease. The potential therapeutic advantage was most strongly apparent in those using acute migraine specific medications, where erenumab 140 mg reduced the number of MSMD to a greater extent than 70 mg. This numerical advantage across outcomes also suggests that for patients started on erenumab 70 mg who report a minimal response initially, the erenumab dose should first be increased to 140 mg before considering a different preventive agent.

Evidence suggests that migraine is a chronic disease that can continually evolve over time.[36] This evolution can involve the transformation from EM to CM, or conversely, to the complete absence of some or all symptoms. It is important to recognize the potential evolutive nature of EM, especially in terms of identifying the risk factors and preventing progression to CM. Evidence suggests that increased headache day frequency, depression, and medication overuse/high-frequency use are the important risk factors for this potential conversion from EM to CM.[37] Our findings suggest that erenumab 140 mg may be better for preventing disease progression, by reducing the potential for conversion from EM to CM, for increasing the likelihood of reversion from CM to EM,[19] and for increasing the probability of reversing acute medication overuse to non-overuse of acute medication.[15] Again, this points to a rationale for considering erenumab 140 mg as the initiation dose for some patients with difficult-to-treat disease, prior treatment failures, and for those most at risk for conversion from EM to CM.

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