{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:02:28Z","timestamp":1791820948092,"version":"4.3.4"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> OnabotulinumtoxinA and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) target different migraine pathways, therefore, combination treatment may provide additional effectiveness for the preventive treatment of chronic migraine (CM) than either treatment alone. The objective of this study was to collect real-world data to improve the understanding of the safety, tolerability, and effectiveness of adding a CGRP mAb to onabotulinumtoxinA treatment for the preventive treatment of CM.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> This was a retrospective, longitudinal study conducted using data extracted from a single clinical site's electronic medical records (EMR) of adult patients (\u226518 years) with CM treated with \u22652 consecutive cycles of onabotulinumtoxinA before \u22651 month of continuous onabotulinumtoxinA and CGRP mAb (erenumab, fremanezumab, or galcanezumab) combination treatment. Safety was evaluated by the rate of adverse events (AE) and serious adverse events (SAE). The proportion of patients who discontinued either onabotulinumtoxinA, a CGRP mAb, or combination treatment, and the reason for discontinuation, if available, was collected. The effectiveness of combination preventive treatment was assessed by the reduction in monthly headache days (MHD). Outcome data were extracted from EMR at the first CGRP mAb prescription (index) and up to four assessments at ~3, 6, 9, and 12 months post-index. The final analyses were based on measures consistently reported in the EMR.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> EMR were collected for 192 patients, of which 148 met eligibility criteria and were included for analysis. Erenumab was prescribed to 56.7% of patients, fremanezumab to 42.6%, and galcanezumab to 0.7%. Mean (standard deviation [SD]) MHD were 20.4 (6.6) prior to onabotulinumtoxinA treatment and 14.0 (6.9) prior to the addition of a CGRP mAb (baseline). After real-world addition of a CGRP mAb, there were significant reductions in MHD at the first assessment (~3 months) (mean \u22122.6 days\/month, 95% CI \u22123.7, \u22121.4) and at all subsequent visits. After ~12 months of continuous combination treatment, MHD were reduced by 4.6 days\/month (95% CI \u22126.7, \u22122.5) and 34.9% of patients achieved \u226550% MHD reduction from index. AEs were reported by 18 patients (12.2%), with the most common being constipation (<jats:italic>n<\/jats:italic> = 8, 5.4% [onabotulinumtoxinA plus erenumab only]) and injection site reactions (<jats:italic>n<\/jats:italic> = 5, 3.4%). No SAEs were reported. Overall, 90 patients (60.8%) discontinued one or both treatments. The most common reason for discontinuing either treatment was lack of insurance coverage (40%); few (~14%) patients discontinued a CGRP mAb and none discontinued onabotulinumtoxinA due to safety\/tolerability.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> In this real-world study, onabotulinumtoxinA was effective at reducing MHD and the addition of a CGRP mAb was safe, well-tolerated and associated with incremental and clinically meaningful reductions in MHD for those who stayed on the combination treatment. No new safety signals were identified. Of those who discontinued, the majority reported lack of insurance coverage as a reason. Prospective real-world and controlled trials are needed to further evaluate the safety and potential benefits of this combination treatment paradigm for people with CM.<\/jats:p>","DOI":"10.3389\/fneur.2021.788159","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T06:33:26Z","timestamp":1641450806000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":52,"title":["Real-World Evidence for the Safety and Efficacy of CGRP Monoclonal Antibody Therapy Added to OnabotulinumtoxinA Treatment for Migraine Prevention in Adult Patients With Chronic Migraine"],"prefix":"10.3389","volume":"12","author":[{"given":"Laszlo","family":"Mechtler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Saikali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"McVige","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Traut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubrey Manack","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1111\/j.1468-2982.2009.01941.x","article-title":"Global prevalence of chronic migraine: a systematic review","volume":"30","author":"Natoli","year":"2010","journal-title":"Cephalalgia."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/0333102417738202","volume":"38","author":"3rd","year":"2018","journal-title":"Cephalalgia"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1111\/head.13613","article-title":"Life with migraine: effects on relationships, career, and finances from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study","volume":"59","author":"Buse","year":"2019","journal-title":"Headache."},{"key":"B4","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1177\/0333102411398400","article-title":"Quality of life impairment, disability and economic burden associated with chronic daily headache, focusing on chronic migraine with or without medication overuse: a systematic review","volume":"31","author":"Lanteri-Minet","year":"2011","journal-title":"Cephalalgia."},{"key":"B5","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1111\/head.12755","article-title":"Direct and indirect costs of chronic and episodic migraine in the united states: a web-based survey","volume":"56","author":"Messali","year":"2016","journal-title":"Headache."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1136\/jnnp-2013-305197","article-title":"Headache-related health resource utilisation in chronic and episodic migraine across six countries","volume":"84","author":"Sanderson","year":"2013","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B7","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1007\/s10194-012-0460-7","article-title":"Cost of healthcare for patients with migraine in five European countries: results from the International Burden of Migraine Study (IBMS)","volume":"13","author":"Bloudek","year":"2012","journal-title":"J Headache Pain."},{"key":"B8","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1177\/2040622315579627","article-title":"The diagnosis and treatment of chronic migraine","volume":"6","author":"Weatherall","year":"2015","journal-title":"Ther Adv Chronic Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"g1416","DOI":"10.1136\/bmj.g1416","article-title":"Chronic migraine","volume":"348","author":"Schwedt","year":"2014","journal-title":"BMJ."},{"key":"B10","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1111\/head.13496","article-title":"The american headache society position statement on integrating new migraine treatments into clinical practice","volume":"59","author":"Charles","year":"2019","journal-title":"Headache."},{"key":"B11","article-title":"The american headache society consensus statement: update on integrating new migraine treatments into clinical practice","volume-title":"Headache","year":"2021"},{"key":"B12","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.mayocp.2015.01.010","article-title":"Best practices for patients with chronic migraine: burden, diagnosis, and management in primary care","volume":"90","author":"Starling","year":"2015","journal-title":"Mayo Clin Proc."},{"key":"B13","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1177\/0333102410364676","article-title":"OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial","volume":"30","author":"Aurora","year":"2010","journal-title":"Cephalalgia."},{"key":"B14","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1177\/0333102410364677","article-title":"OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial","volume":"30","author":"Diener","year":"2010","journal-title":"Cephalalgia."},{"key":"B15","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s10194-018-0840-8","article-title":"Long-term study of the efficacy and safety of onabotulinumtoxinA for the prevention of chronic migraine: COMPEL study","volume":"19","author":"Blumenfeld","year":"2018","journal-title":"J Headache Pain."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1111\/head.13653","article-title":"FORWARD study: evaluating the comparative effectiveness of onabotulinumtoxina and topiramate for headache prevention in adults with chronic migraine","volume":"59","author":"Rothrock","year":"2019","journal-title":"Headache."},{"key":"B17","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s10194-019-0976-1","article-title":"An open-label prospective study of the real-life use of onabotulinumtoxinA for the treatment of chronic migraine: the REPOSE study","volume":"20","author":"Ahmed","year":"2019","journal-title":"J Headache Pain."},{"key":"B18","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/s41582-018-0003-1","article-title":"CGRP as the target of new migraine therapies - successful translation from bench to clinic","volume":"14","author":"Edvinsson","year":"2018","journal-title":"Nat Rev Neurol."},{"key":"B19","article-title":"Thousand Oaks, CA, East Hanover, NJ: Amgen, Inc","year":"2020"},{"key":"B20","article-title":"North Wales, PA: Teva Phamraceuticals USA, Inc","year":"2020"},{"key":"B21","article-title":"Indianapolis, IN: Eli Lilly and Company","year":"2019"},{"key":"B22","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1177\/0333102420905132","article-title":"Eptinezumab in episodic migraine: a randomized, double-blind, placebo-controlled study (PROMISE-1)","volume":"40","author":"Ashina","year":"2020","journal-title":"Cephalalgia."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e1365","DOI":"10.1212\/WNL.0000000000009169","article-title":"Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2","volume":"94","author":"Lipton","year":"2020","journal-title":"Neurology."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1111\/head.13849","article-title":"Mechanism of action of onabotulinumtoxinA in chronic migraine: a narrative review","volume":"60","author":"Burstein","year":"2020","journal-title":"Headache."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1056\/NEJMp048016","article-title":"CGRP-receptor antagonists\u2013a fresh approach to migraine therapy?","volume":"350","author":"Durham","year":"2004","journal-title":"N Engl J Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1111\/head.13843","article-title":"Dual therapy with anti-CGRP monoclonal antibodies and botulinum toxin for migraine prevention: is there a rationale?","volume":"60","author":"Pellesi","year":"2020","journal-title":"Headache."},{"key":"B27","doi-asserted-by":"publisher","first-page":"123","DOI":"10.3390\/toxins11020123","article-title":"Botulinum neurotoxin light chains expressed by defective herpes simplex virus type-1 vectors cleave SNARE proteins and inhibit CGRP release in rat sensory neurons","volume":"11","author":"Joussain","year":"2019","journal-title":"Toxins"},{"key":"B28","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1097\/j.pain.0000000000000119","article-title":"OnabotulinumtoxinA decreases interictal CGRP plasma levels in patients with chronic migraine","volume":"156","author":"Cernuda-Morollon","year":"2015","journal-title":"Pain."},{"key":"B29","doi-asserted-by":"publisher","first-page":"10587","DOI":"10.1523\/JNEUROSCI.2211-17.2017","article-title":"Fremanezumab-a humanized monoclonal anti-CGRP antibody-inhibits thinly myelinated (adelta) but not unmyelinated (C) meningeal nociceptors","volume":"37","author":"Melo-Carrillo","year":"2017","journal-title":"J Neurosci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1177\/0333102419873675","article-title":"Exploring the effects of extracranial injections of botulinum toxin type A on prolonged intracranial meningeal nociceptors responses to cortical spreading depression in female rats","volume":"39","author":"Melo-Carrillo","year":"2019","journal-title":"Cephalalgia."},{"key":"B31","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1177\/0333102410379890","article-title":"Validation of the Headache Impact Test (HIT-6) across episodic and chronic migraine","volume":"31","author":"Yang","year":"2011","journal-title":"Cephalalgia."},{"key":"B32","doi-asserted-by":"publisher","first-page":"S20","DOI":"10.1212\/WNL.56.suppl_1.S20","article-title":"Development and testing of the Migraine Disability Assessment (MIDAS) questionnaire to assess headache-related disability","volume":"56","author":"Stewart","year":"2001","journal-title":"Neurology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15360288.2020.1829249","article-title":"Erenumab and onabotulinumtoxinA combination therapy for the prevention of intractable chronic migraine without aura: a retrospective analysis","volume":"35","author":"Armanious","year":"2021","journal-title":"J Pain Palliat Care Pharmacother."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1857","DOI":"10.1093\/pm\/pnab093","article-title":"Efficacy and tolerability of calcitonin gene-related peptide targeted monoclonal antibody medications as add-on therapy to onabotulinumtoxinA in patients with chronic migraine","volume":"22","author":"Cohen","year":"2021","journal-title":"Pain Med."},{"key":"B35","article-title":"Galcanezumab in the prevention of chronic migraine in patients on botulinum toxin therapy","volume-title":"Neurology","author":"Singh","year":"2020"},{"key":"B36","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1007\/s40122-021-00264-x","article-title":"Real-world evidence for control of chronic migraine patients receiving CGRP monoclonal antibody therapy added to onabotulinumtoxinA: a retrospective chart review","volume":"10","author":"Blumenfeld","year":"2021","journal-title":"Pain Ther."},{"key":"B37","doi-asserted-by":"crossref","DOI":"10.33425\/2639-846X.1037","article-title":"Treatment of chronic migraine with erenumab alone or as an add on therapy: a real-world observational study","volume-title":"Anesth Pain Res.","author":"Boudreau","year":"2020"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1111\/head.13839","article-title":"The effect of adding calcitonin gene-related peptide monoclonal antibodies to Onabotulinum toxin A therapy on headache burden: a retrospective observational case series","volume":"60","author":"Ozudogru","year":"2020","journal-title":"Headache."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e2211","DOI":"10.1212\/WNL.0000000000006640","article-title":"Galcanezumab in chronic migraine: the randomized, double-blind, placebo-controlled REGAIN study","volume":"91","author":"Detke","year":"2018","journal-title":"Neurology."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1001\/jama.2018.4853","article-title":"Effect of fremanezumab compared with placebo for prevention of episodic migraine: a randomized clinical trial","volume":"319","author":"Dodick","year":"2018","journal-title":"JAMA."},{"key":"B41","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.1056\/NEJMoa1709038","article-title":"Fremanezumab for the preventive treatment of chronic migraine","volume":"377","author":"Silberstein","year":"2017","journal-title":"N Engl J Med."},{"key":"B42","volume-title":"The Problem of Underinsurance and How Rising Deductibles Will Make It Worse. The Commonwealth Fund.","author":"Collins","year":"2015"},{"key":"B43","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s10194-020-01111-8","article-title":"From transformation to chronification of migraine: pathophysiological and clinical aspects","volume":"21","author":"Torres-Ferrus","year":"2020","journal-title":"J Headache Pain."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.788159\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T06:33:30Z","timestamp":1641450810000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.788159\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,6]]},"references-count":43,"alternative-id":["10.3389\/fneur.2021.788159"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2021.788159","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,6]]},"article-number":"788159"}}