Where do monoclonal antibodies against the CGRP receptors fit into the treatment algorithm for patients with migraine?

VanderPluym et al report post-hoc analyses from 2 clinical trials to evaluate the effects of fremanezumab on patient’s functional status on their headache free days1. Neurology characterizes the evidence as level 2 that fremanezumab increases normal functional performance on headache free days. The results were robust to multiple functional measures and to both migraine subsets, episodic (8-14 days of headache per month) and chronic (>15 days of headache per month). The authors rightfully describe their findings as exploratory given that these results were not the pre-specified outcomes of these trials. They also point out that the increase in functional performance on headache free days might be just because of the increase in headache free days overall rather than any additional effect on function.

However, the more important question raised by this and other studies of monoclonal antibodies against the CGRP receptors is where do these medications fit into the treatment algorithm for patients with migraine? The Institute for Clinical and Economic Review (ICER) has recently released a report that includes a network meta-analysis to compare the CGRP receptor antibodies to topiramate, amitriptyline, and propranolol for episodic migraine and to topiramate and onabotulinum toxin A for chronic migraine patients. In episodic migraine, they revealed that the reduction in migraine days is approximately 1 day for all of these medications. In chronic migraine, the reduction is approximately 2 days for all interventions. The main caveat being that the number of previously failed medications is likely higher in the CGRP receptor antibody studies, which may make direct comparisons difficult. Despite this limitations, the biggest difference between these medications is cost. The annual drug costs are estimated to be $8500 for both erenumab and fremanezumab compared to less than $400 for topiramate, amitriptyline, and propranolol and $3429 for onabotulinum toxin A. In the episodic migraine patients, the incremental cost effectiveness ratios (ICER) for erenumab was $584,000 per QALY and $466,000 per QALY for fremanezumab when comparing them to other preventative treatments. Similarly, in chronic migraine patients, the ICER was $705,000 per QALY for erenumab and fremanezumab was dominated by current medications. These results show that the new medications have a role in migraine patients, but only after other medications have failed. Given the American Academy of Neurology guidelines which support beta blockers, TCAs, SNRIs, topiramate, and valproic acid, each one of these classes should likely be tried prior to the newer medications. Perhaps, multiple medications in each class should be tried given the costs, although future studies should address whether this is the best approach. CGRP receptor antibodies represent a step forward in migraine treatment, but given the costs and similar effectiveness to currently available medications, prescribing these medications should be reserved for refractory migraine patients.

  1. VanderPluym J, Dodick DW, Lipton RB, Ma Y, Loupe PS, Bigal ME.  Fremanezumab for preventive treatment of migraine: Functional Status on Headache Free Days Neurology Epub 2018 Aug 17
Brian C. Callaghan, MD, MS

Brian C. Callaghan, MD, MS

Dr. Brian Callaghan is an Assistant Professor and health services researcher in the Department of Neurology at the University of Michigan Health System. He is fellowship trained in Neuromuscular Disorders. His research focus is on improving the efficiency of neurologic diagnostic testing. He is specifically interested in neuroimaging for headache, which is one of the most common reasons for a patient to seek medical care. His research has shown that headache neuroimaging is common, costly, increasing over time, and often performed in low risk populations. He has also investigated the appropriateness of diagnostic testing in patients with distal symmetric polyneuropathy. His work has demonstrated a high variation in testing for polyneuropathy with most of the costs driven by MRI and electrodiagnostic studies. He completed a Master’s of Science program in Clinical Research Design and Statistical Analysis at the University of Michigan and a healthcare policy fellowship at the Center for Healthcare Research and Transformation (CHRT). He also serves as a member of the Medical Economics and Management (MEM) and Guideline Development, Dissemination, and Implementation (GDDI) committees of the American Academy of Neurology (AAN).

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