scholarly journals Efficacy and Safety of Monoclonal Antibody Against Calcitonin Gene-Related Peptide or Its Receptor for Migraine: A Systematic Review and Network Meta-analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xing Wang ◽  
Yuqi Chen ◽  
Jinlei Song ◽  
Chao You
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Calcitonin Gene Related Peptide ◽  
Adult Patients ◽  
Related Peptide ◽  
Calcitonin Gene

Background: The optimal monoclonal antibody against calcitonin gene-related peptide (CGRP) for adult patients with migraine has yet to be determined. Therefore, we aimed to compare the effectiveness of different monoclonal antibodies against CGRP or its receptor for adult patients with migraine through a network meta-analysis of randomized controlled trials.Methods: We systematically searched the MEDILNE, Embase, ClinicalTrials.gov, and Cochrane Library databases for relevant publications from inception until October 30, 2020. Only randomized clinical trials of adults with migraine that assessed any calcitonin gene-related peptide monoclonal antibody and reported clinical outcomes were included. The primary outcomes were changes in monthly migraine days and treatment-emergent adverse eventsResults: We initially retrieved 2,070 publications, and ultimately, 18 randomized clinical trials totaling 8,926 patients were included. In terms of efficacy, eptinezumab (MD −1.43, 95% CrI −2.59 to −0.36), erenumab (MD −1.61, 95% CrI −2.40 to −0.84), fremanezumab (MD −2.19, 95% CrI −3.15 to −1.25), and galcanezumab (MD −2.10, 95% CrI −2.76 to −1.45) significantly reduced MMDs compared with placebo. In terms of safety, only galcanezumab increased the incidences of TEAEs (RR 1.11, 95% CrI 1.01–1.22) and serious adverse events (RR 2.95, 95% CrI 1.41–6.87) compared with placebo.Conclusion: Most drugs performed similarly and were superior to placebo in most of our analyses. Further head-to-head research on different types of CGRP monoclonal antibodies is necessary to validate the present findings.

Safety and tolerability of calcitonin-gene-related peptide binding monoclonal antibodies for the prevention of episodic migraine – a meta-analysis of randomized controlled trials

Cephalalgia ◽  
2019 ◽  
Vol 39 (9) ◽  
pp. 1164-1179 ◽  
Author(s):  
Da Xu ◽  
Deng Chen ◽  
Li-na Zhu ◽  
Ge Tan ◽  
Hai-jiao Wang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Adverse Events ◽  
Injection Site ◽  
Meta Analysis ◽  
Peptide Binding ◽  
Episodic Migraine ◽  
Calcitonin Gene Related Peptide ◽  
Serious Adverse Events ◽  
Related Peptide ◽  
Calcitonin Gene

Aim To systematically evaluate the safety and tolerability of calcitonin-gene-related peptide binding monoclonal antibodies from the results of randomized controlled trials. Methods Online databases were searched on calcitonin-gene-related peptide binding monoclonal antibodies for the prevention of episodic migraine. Overall withdrawal, withdrawal due to adverse events, adverse events, serious adverse events and specific adverse events were extracted from the included studies. A meta-analysis was performed with Revman 5.3.0 software. Results Ten studies that investigated four drugs (galcanezumab, erenumab, fremanezumab and eptinezumab) with 5817 participants were included in this study. Serious adverse events, overall withdrawals, withdrawal due to adverse events and any adverse events were not significantly associated with monoclonal antibody treatment. Injection site pain and erythema were significantly higher in the calcitonin-gene-related peptide binding monoclonal antibodies treatment group than in the placebo group. The rates of serious adverse events were significantly higher in the galcanezumab 120 mg group. Injection site erythema was associated with galcanezumab 120 mg and 240 mg. Injection site pain and nasopharyngitis were associated with galcanezumab 150 mg and 5 mg, respectively. Overall adverse events were significantly higher with erenumab 70 mg and 140 mg. Treatment-related adverse events were significantly higher with fremanezumab 225 mg/month and 675 mg/quarter. Conclusions This study provides data on the safety and tolerability profiles of calcitonin-gene-related peptide binding monoclonal antibodies and confirms their potential use as preventive treatments for episodic migraine. In addition to the acceptable withdrawal rates, serious adverse events were rare, and the severity of most adverse events was mild to moderate. Injection site reaction may be the major adverse event associated with galcanezumab.

scholarly journals Effects of Anti-Calcitonin Gene-Related Peptide for Migraines: A Systematic Review with Meta-Analysis of Randomized Clinical Trials

2019 ◽  
Vol 20 (14) ◽  
pp. 3527 ◽  
Author(s):  
I-Hsin Huang ◽  
Po-Chien Wu ◽  
En-Yuan Lin ◽  
Chien-Yu Chen ◽  
Yi-No Kang
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Response Rate ◽  
Meta Analysis ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Long Term Effect ◽  
Calcitonin Gene ◽  
Quantitative Synthesis

We aimed to evaluate the response rate of migraines by using anti-calcitonin gene-related peptide (anti-CGRP) for patients with migraines. We searched three main medical databases up to 29 March 2019. No restriction on language and publication time were applied. Eligible trials included randomized clinical trials investigating a 50%, 75%, and 100% response rate of migraine patients after anti-CGRP intervention. The collected data were dichotomous, and risk ratios (RRs) with a 95% confidence interval (CI) were used to present the quantitative synthesis results. The systematic review identified 16 eligible randomized clinical trials (RCTs) with 9439 patients. Eight of the 16 trials with 2516 patients reported a 50% response rate, and the pooled results showed a significant benefit from anti-CGRP. However, the effects seem to gradually reduce from the first month (RR 1.99, 95% CI 1.59 to 2.49) to the third month (RR 1.48, 95% CI 1.26 to 1.75) of treatment. The magnitude of effect was influenced by the type of anti-CGRP, according to the test for differences between subgroups (I-square = 53%). The funnel plots and Egger’s tests did not show serious small study effects in the results. In conclusion, the current evidences confirmed that anti-CGRP treatment can reduce migraine pain in the short term (within three months), but the long-term effect should be investigated in the future. Moreover, its effects may be influenced by the type and dose of anti-CGRP. Therefore, future studies should make direct comparisons among anti-CGRP medications.

Calcitonin Gene-Related Peptide Antagonists for the Prevention of Migraine: Highlights From Pivotal Studies and the Clinical Relevance of This New Drug Class

2020 ◽  
Vol 54 (8) ◽  
pp. 795-803
Author(s):  
Karissa Arca ◽  
Jenna Reynolds ◽  
Kara A. Sands ◽  
Harn J. Shiue
Keyword(s):  
Monoclonal Antibodies ◽  
Adverse Effects ◽  
Adverse Events ◽  
Clinical Relevance ◽  
Drug Class ◽  
Calcitonin Gene Related Peptide ◽  
Migraine Prophylaxis ◽  
Related Peptide ◽  
New Drug ◽  
Calcitonin Gene

Objective: To review the new drug class of calcitonin gene-related peptide antagonists (monoclonal antibodies) and their clinical relevance in migraine prophylaxis. Data Sources: A literature search was performed in PubMed (January 2009 to November 2019) using the terms migraine, calcitonin gene-related peptide (CGRP), erenumab, fremanezumab, and galcanezumab for clinical trials and studies. Study Selection and Data Extraction: Reports from human studies in English were evaluated for clinical evidence supporting pharmacology, efficacy, and adverse events. Initial pharmacokinetic and preclinical studies were excluded. Data Synthesis: In chronic and episodic migraine, prophylaxis with injections of monoclonal antibodies antagonizing CGRP reduced monthly migraine days with minimal clinically significant adverse events. In addition, there is evidence supporting efficacy in refractory migraine despite optimal prophylaxis. Relevance to Patient Care and Clinical Practice: This is the first target-specific migraine prophylaxis treatment to show efficacy with minimal adverse effects. A higher drug cost is a barrier but is balanced by improved quality of life. Current therapies have limited efficacy and tolerability because of poor side effect profiles. CGRP antagonists represent a shift to more precise migraine treatments. Conclusions: Monoclonal antibodies inhibiting CGRP are effective in migraine prophylaxis with minimal adverse effects. Targeting CGRP is a novel clinical strategy in managing migraine.

Reversible cerebral vasoconstriction syndrome developing after an erenumab injection for migraine prevention

Cephalalgia ◽  
2021 ◽  
pp. 033310242110372
Author(s):  
Todd D Rozen ◽  
Alok A Bhatt
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Illicit Drugs ◽  
Calcitonin Gene Related Peptide ◽  
Reversible Cerebral Vasoconstriction Syndrome ◽  
Related Peptide ◽  
Cerebral Vasoconstriction ◽  
Calcitonin Gene ◽  
Preventive Medication ◽  
New Type

Background Reversible cerebral vasoconstriction syndrome is normally triggered by vasoactive compounds or illicit drugs. A new type of migraine preventive medication blocks calcitonin gene-related peptide utilizing monoclonal antibodies. Calcitonin gene-related peptide is a potent vasodilator for the cerebrovascular system. Could blocking calcitonin gene-related peptide be a trigger for cerebral artery vasospasm in patients susceptible to developing reversible cerebral vasoconstriction syndrome (migraine patients) or in individuals using vasoactive compounds? We present a case of reversible cerebral vasoconstriction syndrome occurring after calcitonin gene-related peptide monoclonal antibody treatment. Case report A 43-year -old woman with a history of episodic migraine developed an acute headache with orgasm two days after taking her second injection of erenumab. Ten days after erenumab injection she developed a thunderclap headache while completing a high intensity workout. These new headaches were only left sided. Computed tomography angiography demonstrated mild to moderate areas of narrowing involving the left middle and anterior cerebral arteries, concerning for reversible cerebral vasoconstriction syndrome. She denied exposure to any known reversible cerebral vasoconstriction syndrome precipitant medication or illicit drugs. She did endorse recent exposure to high altitude prior to erenumab therapy. She was started on verapamil 40 mg three times per day and her headache ceased within 24 h of initiating treatment. A repeat CT angiogram completed 4 weeks after the initial study noted resolution of the areas of vessel stenosis. Conclusion A case of reversible cerebral vasoconstriction syndrome developing after treatment with a calcitonin gene-related peptide monoclonal antibody is presented. The timing of the new type of headache occurring 2 days post erenumab injection suggests a possible cause and effect relationship. Reversible cerebral vasoconstriction syndrome as a possible treatment-related complication to the usage of calcitonin gene-related peptide monoclonal antibodies needs to be studied further.

Fremanezumab autoinjector pen for the prevention of migraine

2021 ◽  
Author(s):  
Mark W Weatherall
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Calcitonin Gene Related Peptide ◽  
Phase Iii ◽  
Tolerability Profile ◽  
Related Peptide ◽  
Phase Iii Clinical Trials ◽  
Humanized Monoclonal Antibody ◽  
Calcitonin Gene ◽  
Favorable Tolerability Profile

Ajovy (fremanezumab, Teva Pharmaceuticals, Israel) is a fully humanized monoclonal antibody that selectively binds both isoforms of the calcitonin gene-related peptide. Calcitonin gene-related peptide is a 37-amino acid neuropeptide involved in central and peripheral pathophysiological events in migraine. It is indicated for prophylaxis of migraine in adults who have at least four migraine days per month, and can be administered as a subcutaneous injection using an autoinjector device, with two dosing options: 225 mg once a month or 675 mg quarterly. In this article, I present data from Phase III clinical trials of fremanezumab in episodic and chronic migraine, in which fremanezumab demonstrated efficacy and had a favorable tolerability profile, with no serious treatment-related adverse events.

scholarly journals Calcitonin Gene-Related Peptide Monoclonal Antibodies Versus Botulinum Neurotoxin a in the Preventive Treatment of Chronic Migraine: An Adjusted Indirect Treatment Comparison Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yao-Yao Chen ◽  
Xiao-Qian Ye ◽  
Tai-Chun Tang ◽  
Tian-Wei She ◽  
Min Chen ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Chronic Migraine ◽  
Botulinum Neurotoxin ◽  
Meta Analysis ◽  
Preventive Treatment ◽  
Calcitonin Gene Related Peptide ◽  
Controlled Trials ◽  
Botulinum Neurotoxin A ◽  
Related Peptide ◽  
Calcitonin Gene

Purpose: Calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are new agents approved by the US Food and Drug Administration for preventive treatment of chronic migraine. Comparison between CGRPmAbs and previously approved Botulinum neurotoxin A (BoNT-A) will inform optimal preventive treatment of chronic migraine, but head-to-head trials are lacking. We therefore aimed to perform adjusted indirect comparison between CGRPmAbs and BoNT-A through a meta-analysis.Methods: OVID MEDLINE, EMBASE and the Cochrane central register of controlled trials, clinical registries, and government websites were searched from inception to September 2019. Randomized controlled trials comparing CGRPmAbs or BoNT-A with placebo in the preventive treatment of chronic migraine were included. The primary outcomes were headache days and migraine days measured at week 12. Data were synthesized by using a frequentist approach; and the treatments were ranked by P-score.Results: We included 10 trials (n = 4,678) after screening 1049 candidates. Six trials were with low risk of bias. Fremanezumab had an effect similar to BoNT-A in the reduction of headache days at week 12 (standard mean difference [SMD] 0.08, 95%CI -0.55 to -0.7). Galcanezumab reduced more migraine days than BoNT-A at week 12 (SMD, -0.94, 95%CI −1.24 to −0.63); fremanezumab showed similar findings (SMD, −0.55, 95%CI −0.85 to −0.24). Galcanezumab and fremanezumab had better effect in mitigating headache impact at week 12. CGRPmAbs and BoNT-A had similar adverse event rate.Conclusion: CGRPmAbs and BoNT-A had similar effect in the preventive treatment of chronic migraine. BoNT-A might be preferentially selected owing to its cost-effectiveness profiles. Further studies with direct comparison of the two treatments are warranted.

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