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Some patients treated with BoNT\u2010A have been reported to develop neutralizing antibodies (NAbs) against BoNT\u2010A, which may result in reduced efficacy and, in some cases, secondary treatment failure (STF). Our aim was to investigate the incidence of STF and NAb positivity after treatment with one of three commercially\u2010available BoNT\u2010A formulations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic review and meta\u2010analysis of STF and\/or NAb positivity after treatment with abobotulinumtoxinA, incobotulinumtoxinA, or onabotulinumtoxinA in patients with CD, spasticity, or blepharospasm was conducted using PubMed, Embase, and Google Scholar.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010nine unique studies reported in 29 publications assessed NAb positivity and were included. The meta\u2010analysis showed that the proportions of patients developing STF were significantly higher after treatment with abobotulinumtoxinA or onabotulinumtoxinA than with incobotulinumtoxinA for CD or spasticity. Depending on the antibody test used, the proportions of patients developing NAbs were also significantly higher after treatment with abobotulinumtoxinA or onabotulinumtoxinA than with incobotulinumtoxinA for CD or spasticity. When data for all indications were pooled, proportions of NAb\u2010positive patients were numerically higher with increasing mean doses of abobotulinumtoxinA or onabotulinumtoxinA. No patients treated exclusively with incobotulinumtoxinA were found to have developed immunogenic STF or persistent NAbs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The risk of developing STF and NAbs appears to vary with indication and BoNT\u2010A formulation. When the efficacy and safety of formulations are comparable, incobotulinumtoxinA may be recommended to avoid developing STF and immunogenicity, particularly for patients requiring higher doses and repeated treatments.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.70289","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T14:50:54Z","timestamp":1753800654000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Systematic Review and Meta\u2010Analysis of Secondary Treatment Failure and Immunogenicity With Botulinum Neurotoxin A in Multiple Indications"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6280-785X","authenticated-orcid":false,"given":"Uwe","family":"Walter","sequence":"first","affiliation":[{"name":"Department of Neurology Rostock University Medical Center  Rostock Germany"},{"name":"German Centre for Neurodegenerative Diseases (DZNE) Research Site Rostock  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillipp","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty Heinrich Heine University  D\u00fcsseldorf Germany"},{"name":"Department of Neurology Maria Hilf Clinics  M\u00f6nchengladbach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warner","family":"Carr","sequence":"additional","affiliation":[{"name":"Allergy and Asthma Associates of Southern California Southern California Research  Mission Viejo California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Hefter","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty Heinrich Heine University  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8304-z"},{"key":"e_1_2_10_3_1","volume-title":"Spasticity in Adults: Management Using Botulinum Toxin. 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