{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T21:31:18Z","timestamp":1785879078948,"version":"3.56.0"},"reference-count":80,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["NET-2016-02361805 (WP 5)"],"award-info":[{"award-number":["NET-2016-02361805 (WP 5)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>OnabotulinumtoxinA, targeting the CGRP machinery, has been approved for the last two decades for chronic migraine prevention. The recently approved monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) pathway open a new age for chronic migraine control. However, some 40% patients suffering from chronic migraine is still resistant to treatment. The aim of this work is to answer the following PICOS (participants intervention comparator outcome study design) question: Is there evidence of efficacy and safety of the combined administration of anti-CGRP mAbs and onabotulinumtoxinA in chronic migraine? A systematic review and meta-analysis [Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations] was made up to 19 April 2022. The results are encouraging: the combined treatment proved to afford \u226550% monthly headache days (MHDs)\/frequency reduction respect to baseline in up to 58.8% of patients; in comparison, anti-CGRP mAbs reduce MHDs of 1.94 days from baseline and botulinum toxin of 1.86 days. Our study demonstrates for the first time that the combination therapy of onabotulinumtoxinA with anti-CGRP mAbs affords a reduction of 2.67 MHDs with respect to onabotulinumtoxinA alone, with moderate certainty of evidence. Adequately powered, good-quality studies are needed to confirm the response to combination therapy in terms of efficacy and safety. PROSPERO registration: CRD42022313640.<\/jats:p>","DOI":"10.3390\/toxins14080529","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T23:49:27Z","timestamp":1659397767000},"page":"529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Pooled Analysis of Real-World Evidence Supports Anti-CGRP mAbs and OnabotulinumtoxinA Combined Trial in Chronic Migraine"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5846-7058","authenticated-orcid":false,"given":"Damiana","family":"Scuteri","sequence":"first","affiliation":[{"name":"Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"},{"name":"Regional Center for Serious Brain Injuries, S. Anna Institute, 88900 Crotone, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4867-1378","authenticated-orcid":false,"given":"Paolo","family":"Tonin","sequence":"additional","affiliation":[{"name":"Regional Center for Serious Brain Injuries, S. Anna Institute, 88900 Crotone, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Nicotera","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maril\u00f9","family":"Vulnera","sequence":"additional","affiliation":[{"name":"Pharmaceutical Service, Provincial Health Authority (ASP), 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina Cristina","family":"Altieri","sequence":"additional","affiliation":[{"name":"Pharmaceutical Service, Provincial Health Authority (ASP), 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assunta","family":"Tarsitano","sequence":"additional","affiliation":[{"name":"Pain Therapy Center, Provincial Health Authority (ASP), 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8540-6218","authenticated-orcid":false,"given":"Giacinto","family":"Bagetta","sequence":"additional","affiliation":[{"name":"Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6472-0697","authenticated-orcid":false,"given":"Maria Tiziana","family":"Corasaniti","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Leonardi, M., Grazzi, L., D\u2019Amico, D., Martelletti, P., Guastafierro, E., Toppo, C., and Raggi, A. 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