Immunogenicity Associated with Botulinum Toxin Treatment (Bellows, Jankovic 2019)
Finnish summary
The study addresses the immunogenicity associated with botulinum toxin treatment and its impact on treatment efficacy. Botulinum toxin (BoNT) is used to treat a wide range of neurological, medical and cosmetic conditions. Two serotypes, type A (BoNT-A) and type B (BoNT-B), are in clinical use. Although they are considered safe and effective, their use is rarely associated with antibody formation, which may reduce or prevent their therapeutic effect.
Key observations:
1. Immunogenicity
- Short dosing intervals and high doses increase the risk of antibody formation.
- Characteristics of some BoNT serotypes, such as composition, preparation and storage, may affect immunogenicity.
- In new formulations with purified core neurotoxin without additional proteins, immunogenicity may be lower.
2. Detection of antibodies
- Several tests for antibody detection (ELISA and mouse-based biological tests) are available for research use.
- Structural tests are sensitive in detecting antibodies, but they cannot distinguish between neutralising and non-neutralising antibodies.
3. Primary and secondary treatment resistance:
- Primary treatment resistance (PNR) refers to a situation where patients do not benefit from BoNT from the first injection.
- Secondary treatment resistance (SNR) occurs when patients initially benefit from an injection but lose this benefit in subsequent rounds of treatment.
4. Patient cases and risk factors:
- Studies have shown that in some patients it can take a long time for antibodies to build up.
- Certain groups of patients, such as those with a history of botulism or vaccination, may be more susceptible to antibody formation.
- Tetanus vaccines have been suggested to affect BoNT antibody formation, but this has not been supported in animal studies.
5. The structure and functioning of the BoNT:
- BoNT consists of nuclear neurotoxins and non-toxic accessory proteins (NAPs).
- BoNT-A and BoNT-B affect different SNARE proteins, which interferes with the release of acetylcholine into the synaptic cleft.
6. Clinical tests and practical recommendations:
- Clinical tests, such as the unilateral eyebrow injection test (UBI), can be used to detect SNR.
- Patients should wait at least 3 months between injections to reduce the risk of antibody formation.
Conclusions:
Botulinum toxin is a safe and effective treatment option for many neurological and non-neurological conditions. Although the formation of neutralising antibodies is a concern, several strategies can reduce the development of immunoresistance, such as using products with a low protein load, avoiding adjuvants, maintaining safe injection intervals and using the lowest possible dose that produces an optimal clinical response.