Prevention of migraine with monoclonal antibodies against CGRP or the CGRP receptor

Diener, Hans‐Christoph; Förderreuther, Stefanie; Gaul, Charly; Giese, Florian; Hamann, Till; Holle-Lee, Dagny; Jürgens, Tim P.; Kamm, Katharina; Kraya, Torsten; Lampl, Christian; May, Arne; Reuter, Uwe; Scheffler, Armin; Tfelt‐Hansen, Peer

doi:10.1186/s42466-020-00057-1

Cited by 41 publications

(19 citation statements)

References 14 publications

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“…However, recent observations demonstrated that CGRP-mAbs prevent the activation of the Aδ-fibers but not C-fibers, whereas BTX-A prevents the activation of the C-fibers but not Aδ-fibers ( 7 , 8 ). Consequently, one can argue that CGRP-mAbs may be effective in migraine patients with predominant involvement of the Aδ-fibers and high-threshold neurons, whereas migraine patients non-responsive to CGRP-mAbs could be characterized by a higher involvement of the C-fibers and/or different central trigeminovascular neurons ( 18 , 19 ). More recently, to provide rational clinical evidences of a combined therapy acting on the trigeminal nociceptive pathway (e.g., both Aδ-fibers and C-fibers), the synergistic effect of BTX-A and erenumab has been evaluated in a cohort of chronic migraine patients ( 11 , 20 ).…”

Section: Discussionmentioning

confidence: 99%

Additive Interaction Between Onabotulinumtoxin-A and Erenumab in Patients With Refractory Migraine

et al. 2021

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In the last decade, notable progresses have been observed in chronic migraine preventive treatments. According to the European Headache Federation and national provisions, onabotulinumtoxin-A (BTX-A) and monoclonal antibodies acting on the pathway of calcitonin gene–related peptide (CGRP-mAbs) should not be administered in combination due to supposed superimposable mechanism of action and high costs. On the other hand, preclinical observations demonstrated that these therapeutic classes, although operating directly or indirectly on the CGRP pathway, act on different fibers. Specifically, the CGRP-mAbs prevent the activation of the Aδ-fibers, whereas BTX-A acts on C-fibers. Therefore, it can be argued that a combined therapy may provide an additive or synergistic effect on the trigeminal nociceptive pathway. In the present study, we report a case series of 10 patients with chronic migraine who experienced significant benefits with the combination of both erenumab and BTX-A compared to each therapeutic strategy alone. A reduction in frequency and intensity of headache attacks (although not statistically significant probably due to the low sample size) was observed in migraine patients treated with a combined therapy with BTX-A and erenumab compared to both BTX-A and erenumab alone. Moreover, the combined therapy with BTX-A and erenumab resulted in a statistically significant reduction in the symptomatic drug intake and in migraine-related disability probably related to a reduced necessity or also to a better responsiveness to rescue treatments. Present data suggest a remodulation of current provisions depriving patients of an effective therapeutic strategy in peculiar migraine endophenotypes.

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Section: Discussionmentioning

confidence: 99%

Additive Interaction Between Onabotulinumtoxin-A and Erenumab in Patients With Refractory Migraine

et al. 2021

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“…It is also stated that, in patients with CM and MOH, the use of anti-CGRP/R mAbs can be initiated before or after withdrawal of acute medications. Several national headache societies have published recommendations on the use of anti-CGRP/R mAbs for migraines [ 96 , 97 , 98 ].…”

Section: Guidelines For the Use Of Mabs In Migraine (American Headache Society/european Headache Federation)mentioning

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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“…However, most of these drugs may lead to numerous adverse events such as dizziness, diarrhea, fatigue, weight gain, or erectile dysfunction, which is believed to be the main reason that drug adherence is very low [11,12]. A relatively new-and first migraine specific-pharmacological strategy is the blockade of the neuropeptide calcitonin gene-related peptide (CGRP) or its receptor by antibodies [13]. However, due to high costs, this approach is currently not routinely offered to all patients [14,15].…”

Section: Introductionmentioning

confidence: 99%

A Digital Health Application Allowing a Personalized Low-Glycemic Nutrition for the Prophylaxis of Migraine: Proof-of-Concept Data from a Retrospective Cohort Study

Schröder

Kühn²,

Kordowski

et al. 2022

JCM

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Background: Migraine is a headache disorder with the highest socioeconomic burden. The aim of this study was to deliver the first proof-of-concept data of the potential role of an individual low-glycemic diet provided by a novel digital health application in the prophylaxis of migraine. Methods: We analyzed data from a retrospective survey of individuals who participated in a digital nutrition program that provides dietary recommendations based on the individual analysis of continuous glucose measurement from an up to 14-day test phase. A total of 84 individuals completed the retrospective digital survey. The endpoints were changes in the number of migraine days, average duration of attacks, average pain severity, frequency of intake of pain medication, absenteeism, and presenteeism before and after program participation. Results: The intraindividual comparisons of the endpoints before and after program participation revealed decreases in migraine frequency and other patient-relevant migraine parameters. Moreover, patients with a baseline migraine frequency of two and more migraine days per month and adherence to the dietary recommendations (n = 40) showed a mean reduction in migraine days by 33% with a 50%-responder rate of 38%. Conclusions: The data provides emerging evidence that an individualized low-glycemic diet based on continuous glucose measurement could be a promising approach for a diet-based, non-pharmacological migraine prophylaxis. However, future research is required to confirm the implied effectiveness.

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Prevention of migraine with monoclonal antibodies against CGRP or the CGRP receptor

Cited by 41 publications

References 14 publications

Additive Interaction Between Onabotulinumtoxin-A and Erenumab in Patients With Refractory Migraine

Additive Interaction Between Onabotulinumtoxin-A and Erenumab in Patients With Refractory Migraine

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

A Digital Health Application Allowing a Personalized Low-Glycemic Nutrition for the Prophylaxis of Migraine: Proof-of-Concept Data from a Retrospective Cohort Study

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