Efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibodies for the preventive treatment of episodic migraine – An updated systematic review and meta-analysis

Deng, Hong; Li, Gaigai; Nie, Hao; Feng, Yangyang; Guo, Guangyu; Guo, Wenliang; Tang, Zhouping

doi:10.21203/rs.2.15211/v2

Cited by 21 publications

(29 citation statements)

References 24 publications

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“…In addition to MSMDs, we performed a subgroup analysis of the above outcomes, which showed that CGRP mAbs showed signi cant e cacy in both episode migraines and chronic migraines, and the results were reliable and stable. The results were similar to those of previous meta-analyses, which included only episodic migraines or chronic migraines [14,[35][36][37].…”

Section: Discussionsupporting

confidence: 89%

Efficacy and Safety of CGRP Monoclonal Antibodies for the Prevention of Migraine Compared with Placebo: A Systematic Review and Meta-Analysis

Chen

et al. 2020

Preprint

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Background: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are a novel class of drugs for migraine that includes erenumab, fremanezumab, galcanezumab and eptinezumab. In clinical trials, CGRP mAbs have been reported to show good efficacy in the prevention of episodic migraines or chronic migraines. Our aim was to evaluate the efficacy and safety of CGRP monoclonal antibodies in this study.Methods: We systematically searched for randomized controlled trials in the PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases. The primary outcome was overall mean change from baseline to end of treatment in the number of monthly migraine headache days (MMHDs). The secondary outcomes included 50% response rate, in the number of monthly headache days (MHDs), in the number of monthly headache hours (MHHs), and in the number of monthly acute migraine-specific medication days (MSMDs). The safety outcomes were evaluated in terms of reported adverse events. Results: Eighteen studies including 11,099 patients were included in the meta-analysis. The meta-analysis showed that CGRP mAbs exhibited a significant benefit in reducing the number of MMHDs compared to placebo (Episodic migraine: Std. MD -0.42, 95% CI -0.47 to -0.36; Chronic migraine: Std. MD -0.28, 95% CI -0.35 to -0.21). Similarly, CGRP mAbs were superior to placebo in the secondary outcomes of 50% response rate, MHDs, MHHs, and MSMDs. With respect to safety, serious adverse events and withdrawal due to adverse events were not significantly associated with CGRP mAbs. Fremanezumab was associated with a significantly higher incidence of any adverse event compared with placebo (RR 1.10, 95% CI 1.03 to 1.17). Galcanezumab was associated with significantly higher treatment-emergent adverse events compared with placebo (RR 1.11, 95% CI 1.04 to 1.17). Constipation and injection site pain were significantly higher with erenumab than placebo. Injection site erythema and injection site induration were significantly higher with fremanezumab than placebo. Upper respiratory tract infection, injection site erythema, injection site pruritus and injection site reaction were significantly higher with galcanezumab than placebo. Conclusions: This study confirms that CGRP mAbs are effective as preventive treatments for episodic migraines and chronic migraines. Adverse reactions at the injection site were associated with erenumab, fremanezumab and galcanezumab therapy. Constipation was more common with erenumab. The risk of upper respiratory tract infection was higher with galcanezumab.Systematic review registration: Our PROSPERO protocol registration number: CRD42019125928. Registered 26 November 2019.

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Section: Discussionsupporting

confidence: 89%

Efficacy and Safety of CGRP Monoclonal Antibodies for the Prevention of Migraine Compared with Placebo: A Systematic Review and Meta-Analysis

Chen

et al. 2020

Preprint

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“…With this abundance of free circulating CGRP, it should not be surprising that rimegepant acute treatment could provide additional therapeutic benefit. Since the 3 ligand‐targeting CGRP mAbs (fremanezumab, galcanezumab, eptinezumab) exhibit similar treatment effects on migraine prevention, 27 it is likely that all 3 leave comparable free levels of CGRP circulating during mAb treatment.…”

Section: Discussionmentioning

confidence: 99%

Safety of Rimegepant, an Oral CGRP Receptor Antagonist, Plus CGRP Monoclonal Antibodies for Migraine

et al. 2020

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Objective Evaluate the safety and tolerability of oral rimegepant when used for acute treatment concomitantly with a monoclonal antibody (mAb) targeting the calcitonin gene‐related peptide (CGRP) ligand or receptor (CGRP mAb) for the preventive treatment of migraine. Background The efficacy of CGRP mAbs for the preventive treatment of migraine and the small molecule CGRP receptor antagonist rimegepant for acute treatment has been demonstrated in randomized controlled clinical trials. Over the past few years, the US Food and Drug Administration has approved 4 CGRP mAbs for the preventive treatment of migraine and 2 small molecule CGRP receptor antagonists for the acute treatment of migraine. A previous case report of 2 patients receiving concomitant treatment with rimegepant and erenumab suggested that rimegepant may be safely used as acute treatment in patients who are also receiving a preventive regimen involving CGRP mAbs. We report here 13 additional patients with migraine who simultaneously used rimegepant and either erenumab, fremanezumab, or galcanezumab and assess the rate of on‐treatment adverse events (AEs). Methods This was a substudy nested within a multicenter, open‐label, long‐term safety study in adults with 2‐14 monthly migraine attacks of moderate to severe pain intensity. A subgroup experiencing 2‐8 monthly attacks and taking a stable dose of a CGRP mAb also took rimegepant 75 mg as needed up to once daily for acute treatment for 12 weeks. Results The 13 patients (11 women [85%]; mean age 49.9 years) enrolled in the substudy were being treated with CGRP mAbs (erenumab [n = 7], fremanezumab [n = 4], or galcanezumab [n = 2]). Mean (SD) time in the rimegepant treatment period was 9.6 (4.6) weeks. Mean (SD) 4‐week rimegepant exposure was 7.8 (5.5) doses; a total of 224 doses were taken. Five (38%) patients reported ≥1 on‐treatment AE. Of these, 2 (15%) patients had mild or moderate nasopharyngitis; no other AEs occurred in ≥2 patients. Three patients had AEs of mild or moderate severity that were considered potentially treatment‐related. No patients had serious AEs, AEs leading to discontinuation, or aminotransferase levels >3× the upper limit of normal. Conclusion Rimegepant, when used as an oral acute treatment in patients receiving CGRP mAbs as preventive treatment, was well tolerated; no safety issues were identified. Studies involving larger patient populations are needed to confirm these findings.

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“…Calcitonin gene-related peptide (CGRP), a 37-amino-acid neuropeptide, is widely distributed in central and peripheral nervous system (17,18). It is well documented that CGRP is essential for the modulation of orofacial pain, especially migraine (19,20). Our previous study revealed that CGRP played an important role in the modulation of orofacial pain (21).…”

Section: Introductionmentioning

confidence: 98%

N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways

Yan

Han

Zhang

et al. 2020

Preprint

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Background: Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation. Calcitonin gene-related peptide (CGRP) is a well-known pro-nociceptive molecule that participates in the modulation of orofacial pain. We aimed to determine the effects of N/OFQ on the modulation of orofacial pain and on the release of CGRP.Methods: Orofacial pain model was established by ligating springs between incisors and molars in rats for the simulation of tooth movement. The expression level of N/OFQ was determined and pain level scored in response to orofacial pain. Both agonist and antagonist of N/OFQ receptor were administered to examine their effects on pain and the expression of CGRP in trigeminal ganglia (TG). Moreover, gene therapy based on the overexpression of N/OFQ was delivered to validate the modulatory role of N/OFQ on pain and CGRP expression.Results: Tooth movement elicited orofacial pain and an elevation in N/OFQ expression. N/OFQ exacerbated orofacial pain and upregulated CGRP expression in TG, while UFP-101 alleviated pain and downregulated CGRP expression. N/OFQ-based gene therapy was successful in overexpressing N/OFQ in TG, which resulted in pain exacerbation and elevation of CGRP expression in TG.Conclusions: N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.

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Efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibodies for the preventive treatment of episodic migraine – An updated systematic review and meta-analysis

Cited by 21 publications

References 24 publications

Efficacy and Safety of CGRP Monoclonal Antibodies for the Prevention of Migraine Compared with Placebo: A Systematic Review and Meta-Analysis

Efficacy and Safety of CGRP Monoclonal Antibodies for the Prevention of Migraine Compared with Placebo: A Systematic Review and Meta-Analysis

Safety of Rimegepant, an Oral CGRP Receptor Antagonist, Plus CGRP Monoclonal Antibodies for Migraine

N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways

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