Antibody‐induced botulinum toxin treatment failure: A review and novel management approach

Abstract

Background Botulinum neurotoxin A (BoNT/A) has been used for cosmetic indications for many decades. Consumption of BoNT/A usage has been markedly increased for a few years. Even new formulations of BoNT/A to decrease immunogenicity have been released, repeated treatment to maintain efficacy outcome is inevitable and could finally provoke immune response. In the past, prevalence of botulinum treatment failure (BTF) in cosmetic indication was rare leading to less medical concern. Current decade, case reports on BTF, especially antibody‐induced botulinum toxin treatment failure (ABTF), have been increasingly revealed and risk factors associated with ABTF have been intensively studied. Aims In this article, we will review antibody‐induced botulinum toxin treatment failure (ABTF), risk‐associated ABTF, prevalence and recent case reports of ABTF, and new approach to deal with ABTF. Methods Literature search was conducted using PubMed. The relevant literatures published between January 2000 and May 2020 concerning BTF and ABTF including investigation for ABTF were included and analyzed. Results Possible causes of BTF were summarized. ABTF could be a tip of iceberg of BTF, its prevalence, and currently, 10‐year case reports of ABTF were published evidence. Risk factors and investigation methods for ABTF were also summarized. Based on previous studies and our experience, novel approach to management of ABTF was described. Conclusion Effective management of BTF is to explore causes of treatment failure. Antibodies against BoNT/A complex could be one of many possibilities. Laboratory in vitro tests could be alternative tools to decrease adverse effect and rebooting immune responses in BTF patients.

An Update on the Cosmetic Use of Botulinum Toxin: The Pattern of Practice among Korean Dermatologists

“…This finding implies that BoNT-A resistance does not have substantial clinical impact in cosmetic settings. Nevertheless, when antibody-induced resistance is suspected, history of BoNT-A exposure should be thoroughly explored, followed by laboratory investigations according to the algorithm suggested by Srinoulprasert et al [ 15 ]. Inhibition ELISA (detects antibody against all active sites of BoNT-A) and absorption ELISA (detects antibodies against accessory or complexing proteins) as well as functional tests are mentioned in the algorithm [ 16 ].…”

Immunogenicity Associated with Aesthetic Botulinumtoxin A: A Survey of Asia-Pacific Physicians’ Experiences and Recommendations

“…Although some anti-BoNT/A antibody tests were recently published (R Wanitphakdeedecha) 13 , 18 and other experts have developed their own assays (YY Chao), improvements in test accuracy or specificity are needed to differentiate nonneutralizing antibodies from nAbs. It is important to bear in mind that clinical nonresponse might also be due to suboptimal treatment, such as incorrect injection techniques or product reconstitution.…”

“…Increasingly, aesthetic physicians are encountering secondary nonresponse or "toxin resistance" due to neutralizing antibodies (nAbs) against BoNT/A ("anti-BoNT/A") after treatment for cosmetic indications. [5][6][7][8][9][10][11][12] Secondary treatment failure (STF) is defined as an initial response to BoNT/A followed by variable loss of clinical responsiveness 13 over time with repeated injections. 14 Partial STF (PSTF) is suspected when achieving the same clinical response requires higher doses of BoNT/A ("dose creep"), or the duration of effect is shorter when using the same dose ("interval creep").…”

Immunogenicity of Botulinum Toxin Formulations: Potential Therapeutic Implications

“…The therapeutic use of BoNT in chronic conditions is potentially lifelong, and, given the bacterial origins of BoNT, repeated exposure can elicit antibody formation leading to clinical nonresponsiveness [2,3]. Reports of immunogenicity after long-term treatment with some BoNT formulations are increasingly emergent [4][5][6][7][8][9][10][11][12][13], with varying outcomes dependent on factors such as diagnosis, BoNT formulation, prior BoNT treatment, neurotoxin complex protein load, injection session dose, treatment duration, and length of reinjection interval [3,[14][15][16].…”