Monoclonal Antibodies against Calcitonin Gene-Related Peptide for Migraine Prophylaxis: A Systematic Review of Real-World Data

Pavelic, Antun R; Wöber, Christian; Riederer, Franz; Zebenholzer, Karin

doi:10.3390/cells12010143

Cited by 34 publications

(20 citation statements)

References 175 publications

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“…Regarding the clinical studies of CGRP, many data remain unavailable, including data on interictal M0, MA, CM, and central NP. Hopefully, more clinical studies will reveal the consequences of CGRP modulator administration to clarify its efficacy in those subtypes of pain disorders [ 222 , 223 , 224 , 225 , 226 ]. Different TRP ion channels play distinct roles in both migraine and NP [ 227 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain

Tajti

Delia

Csáti

et al. 2023

IJMS

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Migraine and neuropathic pain (NP) are both painful, disabling, chronic conditions which exhibit some symptom similarities and are thus considered to share a common etiology. The calcitonin gene-related peptide (CGRP) has gained credit as a target for migraine management; nevertheless, the efficacy and the applicability of CGRP modifiers warrant the search for more effective therapeutic targets for pain management. This scoping review focuses on human studies of common pathogenic factors in migraine and NP, with reference to available preclinical evidence to explore potential novel therapeutic targets. CGRP inhibitors and monoclonal antibodies alleviate inflammation in the meninges; targeting transient receptor potential (TRP) ion channels may help prevent the release of nociceptive substances, and modifying the endocannabinoid system may open a path toward discovery of novel analgesics. There may exist a potential target in the tryptophan-kynurenine (KYN) metabolic system, which is closely linked to glutamate-induced hyperexcitability; alleviating neuroinflammation may complement a pain-relieving armamentarium, and modifying microglial excitation, which is observed in both conditions, may be a possible approach. Those are several potential analgesic targets which deserve to be explored in search of novel analgesics; however, much evidence remains missing. This review highlights the need for more studies on CGRP modifiers for subtypes, the discovery of TRP and endocannabinoid modulators, knowledge of the status of KYN metabolites, the consensus on cytokines and sampling, and biomarkers for microglial function, in search of innovative pain management methods for migraine and NP.

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Section: Discussionmentioning

confidence: 99%

Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain

Tajti

Delia

Csáti

et al. 2023

IJMS

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“…Without a doubt, anti-CGRP treatments demonstrate promising efficacy and tolerability in a significant number of patients in both clinical trials and realworld studies (116)(117)(118)(119)(120)(121)(122)(123)(124). Furthermore, comparisons with older oral preventive drugs in real-world studies have revealed favorable results, both in terms of efficacy and tolerability (125,126).…”

Section: Anti-cgrp Medication and Medication Underusementioning

confidence: 99%

Medication “underuse” headache

Rattanawong,

Rapoport,

Srikiatkhachorn

2024

Cephalalgia

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Background Many risk factors have been associated with migraine progression, including insufficient and ineffective utilization of migraine medications; however, they have been inadequately explored. This has resulted in suboptimal usage of medications without effective altering of prescribing recommendations for patients, posing a risk for migraine chronification. Methods Our aim is to conduct a comprehensive review of the available evidence regarding the underuse of migraine medications, both acute and preventive. The term “underuse” includes, but is not limited to: ( 1 ) ineffective use of appropriate and inappropriate medication; ( 2 ) underutilization; ( 3 ) inappropriate timing of usage; and ( 4 ) patient dissatisfaction with medication. Results The underuse of both acute and preventive medications has been shown to contribute to the progression of migraine. In terms of acute medication, chronification occurs as a result of insufficient drug use, including failure of the prescriber to select the appropriate type based on pain intensity and disability, patients taking medication too late (more than 60 minutes after the onset or after central sensitization has occurred as evidenced by allodynia), and discontinuation because of lack of effect or intolerable side effects. The underlying cause of inadequate effectiveness of acute medication lies in its inability to halt the propagation of peripheral activation to central sensitization in a timely manner. For oral and injectable preventive migraine medications, insufficient efficacy and intolerable side effects have led to poor adherence and discontinuation with subsequent progression of migraine. The underlying pathophysiology here is rooted in the repetitive stimulation of afferent sensory pain fibers, followed by ascending brainstem pain pathways plus dysfunction of the endogenous descending brainstem pain inhibitory pathway. Although anti-calcitonin gene-related peptide (CGRP) medications partially address pain caused by the above factors, including decreased efficacy and tolerability from conventional therapy, some patients do not respond well to this treatment. Research suggests that initiating preventive anti-CGRP treatment at an early stage (during low frequency episodic migraine attacks) is more beneficial than commencing it during high frequency episodic attacks or when chronic migraine has begun. Conclusions The term “medication underuse” is underrecognized, but it holds significant importance. Optimal usage of acute care and preventive migraine medications could potentially prevent migraine chronification and improve the treatment of migraine attacks.

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“…The CGRP monoclonal antibodies and the gepants are generally well tolerated. In clinical trials, the most commonly reported adverse events with the CGRP monoclonal antibodies are constipation and injection site reactions 26 . With respect to relative tolerability, in a meta-analysis of 19 clinical trials of CGRP monoclonal antibodies and gepants, 8 atogepant 60 mg 2 times a day (this dose does not have regulatory approval; odds ratio [OR]: 2.22; 95% confidence interval [CI]: 1.26 to 3.91) and galcanezumab 240 mg (OR: 1.63; 95% CI: 1.33 to 2.00) were most likely to be associated with treatment-emergent adverse events.…”

Section: Cgrp-targeted Migraine Preventive Medicationsmentioning

confidence: 99%

Preventive Treatment of Migraine

Lipton

2024

CONTINUUM: Lifelong Learning in Neurology

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OBJECTIVE This article describes strategies for the preventive treatment of migraine including the emerging role of calcitonin gene-related peptide (CGRP)-targeted therapies and introduces novel paradigms for the preventive treatment of migraine. LATEST DEVELOPMENTS Multiple migraine medications targeting CGRP have been introduced since 2018, including injectable monoclonal antibodies (ie, eptinezumab, erenumab, fremanezumab, and galcanezumab) and oral small-molecule CGRP receptor antagonists (ie, ubrogepant, rimegepant, atogepant, and zavegepant). With the exceptions of ubrogepant and zavegepant, which are approved only as acute treatments, all of these agents have demonstrated efficacy in the preventive treatment of migraine; the monoclonal antibodies and atogepant have evidence of effectiveness in adults with either episodic or chronic migraine. The safety and tolerability profiles of CGRP-targeted therapies in migraine are favorable. ESSENTIAL POINTS The goals of preventive migraine therapy include reducing the frequency, severity, duration, and disability associated with attacks, reducing the need for acute treatment and the risk of medication overuse, enhancing self-efficacy and health-related quality of life, and reducing headache-related distress and interictal burden. Six drugs targeting CGRP (four monoclonal antibodies and two gepants) are now available for the preventive treatment of episodic migraine in adults. The efficacy of CGRP-targeted medications in the acute and preventive treatment of migraine, together with good safety and tolerability, has led to the emergence of new approaches to preventive treatment.

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Monoclonal Antibodies against Calcitonin Gene-Related Peptide for Migraine Prophylaxis: A Systematic Review of Real-World Data

Cited by 34 publications

References 175 publications

Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain

Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain

Medication “underuse” headache

Preventive Treatment of Migraine

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