{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:48:30Z","timestamp":1785836910669,"version":"3.56.0"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Background: A substantial proportion of patients with chronic migraine (CM) with previous failures among oral standard-of-care migraine medications do not respond to monoclonal antibodies targeting the calcitonine gene related peptide pathway (CGRP-mAbs), leaving limited evidence-based options for subsequent preventive strategies. The present multicentre real-world study evaluated the effectiveness of onabotulinumtoxin-A (BoNT-A) in CM patients with previous CGRP-mAb failure and multiple prior oral preventive failures. Methods: This prospective, observational, non-randomized multicentre study enrolled patients with CM who had failed \u22653 classes of oral preventive treatments and \u22651 CGRP-mAb due to lack of efficacy or intolerance. Participants received BoNT-A according to the PREEMPT \u201cfollow-the-pain\u201d paradigm every three months and were followed for 6 months. Co-primary outcomes were change in monthly headache days (MHD) after three and six months and \u226550% MHD responder rates at both time points. Results: Fifty-three patients were analysed (85% female, aged 48.5 \u00b1 15.2 years, range 20\u201373). Compared to the baseline, at the third month and sixth month, MHD decreased from 22.83 (SD 6.74) to 15.38 (SD 7.91; p &lt; 0.001) and 14.55 (SD 9.35; p &lt; 0.001), respectively. The percentages of participants achieving the response status in MMD at the third month and sixth month were 30% and 45%, respectively. In the third and sixth months, 22 patients (41.5%) and 27 patients (50.9%), respectively, converted from chronic to episodic migraine, while the prevalence of medication-overuse headache decreased from 81.1% of patients at baseline to 45.3% and 43.4%, respectively. Migraine-related impact and disability scores improved over follow-up, alongside improvements in anxiety and depressive symptoms and in migraine-specific quality of life. Conclusions: The present findings support the use of BoNT-A in difficult-to-treat patients with CM following CGRP-mAb failure and provide further evidence that its therapeutic effects may rely on mechanisms that are at least partially distinct from, and potentially complementary to, those of CGRP-targeted therapies.<\/jats:p>","DOI":"10.3390\/toxins18080342","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:15:22Z","timestamp":1785834922000},"page":"342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effectiveness of Onabotulinumtoxin-A in Patients with Chronic Migraine and Previous CGRP-mAb Treatment Failure: A Multicentre 6-Month Real-World Experience"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3288-1685","authenticated-orcid":false,"given":"Marcello","family":"Silvestro","sequence":"first","affiliation":[{"name":"Inter-Departmental Program of Headache Medicine and Primary Pain Syndromes, Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5113-2017","authenticated-orcid":false,"given":"Maria","family":"Albanese","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Unit of Neurology, IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Orologio","sequence":"additional","affiliation":[{"name":"Inter-Departmental Program of Headache Medicine and Primary Pain Syndromes, Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3598-0195","authenticated-orcid":false,"given":"Luigi Francesco","family":"Iannone","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0790-4240","authenticated-orcid":false,"given":"Francesca","family":"Pistoia","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2887-7624","authenticated-orcid":false,"given":"Stefania","family":"Battistini","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Neurological Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2878-560X","authenticated-orcid":false,"given":"Gianluca","family":"Avino","sequence":"additional","affiliation":[{"name":"Neurology Unit, Ospedale Santo Stefano, USL Toscana Centro, 59100 Prato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Petracca","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Romozzi","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Ornello","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Centonze","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Unit of Neurology, IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0651-1939","authenticated-orcid":false,"given":"Simona","family":"Sacco","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Russo","sequence":"additional","affiliation":[{"name":"Inter-Departmental Program of Headache Medicine and Primary Pain Syndromes, Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Italian Headache Registry (RICe) Study 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