In Response to Recommendations on the Use of Anti-CGRP Monoclonal Antibodies in Children and Adolescents

In one study, up to 24% of pediatric migraine will be refractory to conventional treatment and/or not respond to the treatments recommended in the recently published practice guideline update summary: pharmacological treatment for pediatric migraine prevention. Excluded in the guidelines is the academically correct position that no recommendations can be made for the use of calcitonin gene related peptide (CGRP) monoclonal in children under age 18 because they were not included in the studies that led to food and drug administration (FDA) approval of this class of drugs. The first monoclonal antibody was FDA approved and released for general use in adults in May 2018. There are no published studies on efficacy of CGRP monoclonal antibodies (mAbs) in those under the age of 18. However, recognizing that there are children who fail conventional and guideline driven treatments, Szperka et al published recommendations on the use of anti-CGRP mAbs in children and adolescents which states that it’s reasonable to use CGRP mAbs in children under 18 if they fail 2 or more conventional treatments rather than waiting for the results of large-scale studies that will take years to complete. According to the guidelines, evidence for pharmacologic prevention of migraines in children and adolescents is limited. In the 15 studies included in a literature review, there was not sufficient evidence to show preventive treatments, such as divalproex, onabotulinumtoxin A, amitriptyline, nimodipine, and flunarizine, were more effective than placebo at reducing the frequency of headaches. There was some evidence to show propranolol in children and cognitive behavioral therapy, topiramate, and cinnarizine in children and adolescents can reduce headache frequency. However, cinnarizine is not available in the United States. Topiramate may cause cognitive dysfunction. Beta-blockers cannot be given to those with asthma which is highly comorbid with migraine, and they are not tolerated by athletes. There is a high placebo rate in pediatric trials and there is a need to complete the CGRP mAb trials in the under age 18 group. However, not treating the nonresponders of the guidelines drug list and other evidence-based therapies with CGRP mAbs that are safe and effective in adults will only place these children at risk for progression to chronic and refractory chronic migraine. Chronic migraine has been shown to develop as a consequence of migraine progression which is correlated to migraine frequency in adults, adolescents, and childr Reducing attack frequency with effective preventative therapy is an effective tool to improve children and adolescent’s lives and prevent progression to chronic migraine. Repeated episodes of central sensitization are associated with permanent neuronal damage, treatment refractoriness, and disease progression. Trigeminovascular fibers projecting to the meninges are activated during a migraine attack, neuropeptide CGRP is released and a sterile inflammation is characterized by plasma protein leakage, mast cell activation, and vasodilatation. These changes lead to sensitization of the first-order trigeminal neurons, explaining pulsating pain, pain aggravated by movements of the head, bending down, and physical exercise. Sensitization of the second-order neurons in the brainstem, particularly the trigeminal nucleus caudalis, accounts for cephalic allodynia. Extracephalic allodynia (limb and trunk) can be explained by sensitization of the third-order trigeminal neurons, which project from thalamus to Headache doi: 10.1111/head.13710 © 2019 American Headache Society Published by Wiley Periodicals, Inc. ISSN 0017-8748