Calcitonin Gene–Related Peptide Monoclonal Antibody Use for the Preventive Treatment of Refractory Headache Disorders in Adolescents

Greene, Kaitlin; Gentile, Carlyn Patterson; Szperka, Christina L.; Yonker, Marcy; Gelfand, Amy A.; Grimes, Barbara; Irwin, Samantha

doi:10.1016/j.pediatrneurol.2020.09.014

Cited by 43 publications

(40 citation statements)

References 21 publications

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“…From the RWE point of view, the new treatments go under the “crash test”, administered in patients with comorbidities and those highly refractory to treatments. Furthermore, real-world data from a cohort study including adolescents with refractory headache disorders revealed a treatment benefit [ 99 ]. This is encouraging as pediatric patients do not have many therapeutic options in their arsenal so far.…”

Section: Discussionmentioning

confidence: 99%

Monoclonal Antibodies Targeting CGRP: From Clinical Studies to Real-World Evidence—What Do We Know So Far?

et al. 2021

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Now more than ever is the time of monoclonal antibody use in neurology. In headaches, disease-specific and mechanism-based treatments existed only for symptomatic management of migraines (i.e., triptans), while the standard prophylactic anti-migraine treatments consist of non-specific and repurposed drugs that share limited safety profiles and high risk for interactions with other medications, resulting in rundown adherence rates. Recent advances in headache science have increased our understanding of the role of calcitonin gene relate peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) pathways in cephalic pain neurotransmission and peripheral or central sensitization, leading to the development of monoclonal antibodies (mAbs) or small molecules targeting these neuropeptides or their receptors. Large scale randomized clinical trials confirmed that inhibition of the CGRP system attenuates migraine, while the PACAP mediated nociception is still under scientific and clinical investigation. In this review, we provide the latest clinical evidence for the use of anti-CGRP in migraine prevention with emphasis on efficacy and safety outcomes from Phase III and real-world studies.

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Section: Discussionmentioning

confidence: 99%

Monoclonal Antibodies Targeting CGRP: From Clinical Studies to Real-World Evidence—What Do We Know So Far?

et al. 2021

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“…Another new study by Greene et al 73 showed that adolescents (mean age 15.9 ± 1.4) with treatment-refractory chronic migraine had significant effect from treatment with anti-CGRP and anti-CGRP receptor mAbs compared with baseline, with 71.5% reporting benefit at first follow-up (mean 2.7 months after initiation of treatment) and 69.8% at second follow-up (mean 4.6 months after initiation of treatment). Although the study was not placebo-controlled, the authors believe that the placebo response would be limited in this group of patients, whose headache had been refractory to multiple outpatient and inpatient treatments.…”

Section: Cgrp In Pediatric Patients With Migrainementioning

confidence: 96%

“…Anti-CGRP and anti-CGRP-receptor antibodies have been shown to be effective as migraine prophylaxis. 80 One observational study 73 showed that adolescents with treatment refractory chronic migraine had significant effect from treatment with anti-CGRP and anti-CGRP receptor antibodies. Intravenous injection of CGRP causes migraine in adult migraineurs, [58][59][60] and these attacks are reversible by treatment with triptans.…”

Section: Cgrp In Pediatric Patients With Migrainementioning

confidence: 99%

Migraine Pathophysiology in Children and Adolescents: A Review of the Literature

2022

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Although migraine in adult and pediatric patients are overall very similar to each other, differences in prevalence, presentation, and treatment efficacy may reflect slight differences in the pathophysiological processes underlying migraine in these patient groups, perhaps because of ongoing development of the nervous system during childhood and adolescence. Although major gains have been made in understanding the pathophysiology of migraine in adults in recent years, equivalent research on migraine in pediatric patients continues to lag behind. In this review, we will describe the current state of migraine research in pediatric patients with regard to presentation and frequency of prodromal and postdromal symptoms, ictal and interictal calcitonin gene-related peptide elevation, and evidence for cortical spreading depression, thus covering all phases of migraine, and discuss how the findings seen here may relate to possible underlying pathophysiological mechanisms of migraine. We aim to elucidate possible differences between migraine in children and adults, and the need for further research specific to pediatric patients with migraine in order to improve treatment in this patient group.

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“…However, in an open multicentre retrospective chart review, 112 adolescents who had received at least one dose of a CGRP ligand/receptor antibody were analysed [ 24 ]. Mean age at first dose was 15.9 years.…”

Section: Cgrp Ligand/receptor Antibodies In Children and Adolescentsmentioning

confidence: 99%

CGRP in Childhood and Adolescence Migraine: (Patho)physiological and Clinical Aspects

Evers

2022

Curr Pain Headache Rep

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Purpose of Review To summarise and analyse the current knowledge of CGRP metabolism in childhood and adolescence and its role in childhood and adolescence migraine. Recent Findings Influencing CGRP pathways is nowadays one of the main mechanisms to treat migraine. In adults, several clinical trials with different drug classes have supported this finding. However, only very little is known on these mechanisms in children and adolescents with migraine. Based on a literature search, it can be concluded that substantial parts of the CGRP pathways are already developed and working in the preterm fetus of animals. Newborn animals show high CGRP levels and high density of CGRP positive neurons and nerve fibres. In human studies, increased levels of CGRP were observed in childhood and adolescent migraine patients. Remedies based on influencing CGRP metabolism are also working in that age group. For triptans, this has clearly been shown; for gepants, no data are available, and for CGRP ligand/receptor antibodies, positive evidence is only available from case series. Summary Only very little is known on CGRP metabolism in childhood and adolescence. However, placebo-controlled clinical trials both on CGRP antagonists and on CGRP ligand/receptor antibodies are under way and will show in some years whether these drug classes are efficacious also in children and adolescents.

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Calcitonin Gene–Related Peptide Monoclonal Antibody Use for the Preventive Treatment of Refractory Headache Disorders in Adolescents

Cited by 43 publications

References 21 publications

Monoclonal Antibodies Targeting CGRP: From Clinical Studies to Real-World Evidence—What Do We Know So Far?

Monoclonal Antibodies Targeting CGRP: From Clinical Studies to Real-World Evidence—What Do We Know So Far?

Migraine Pathophysiology in Children and Adolescents: A Review of the Literature

CGRP in Childhood and Adolescence Migraine: (Patho)physiological and Clinical Aspects

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