Antibody-induced failure of botulinum toxin therapy

Abstract

Botulinum toxin (BT) has been used with great success in a large number of medical specialities. In some patients, however, formation of antibodies against BT (BTAB), with therapy failure (ABTF) occurs. Risk factors for ABTF are the amount of BT given at each injection series and the duration of the intervals between injection series. Treatment time and cumulative BT dose as well as patient age and gender are not independent risk factors. BTAB titres drop spontaneously after cessation of BT therapy, but latencies are too long to be compatible with a clinically effective therapy. Once these titres have dropped, BT therapy can be restarted using improved parameters and improved BT preparations with lower antigenicity. Increasing the BT dosage can be successful for overcoming ABTF when BTAB titres are low and target muscle responses are only moderately reduced. The use of alternative BT type A preparations fails to overcome ABTF. Alternative BT types such as types B and F are initially successful in ABTF but stimulate the formation of antibodies against the alternative BT types after few applications. When type B is used, substantial systemic anticholinergic side effects can occur. Prevention of BTAB formation is of paramount importance. Risk factors for BTAB formation have to be taken into account when planning BT therapy. The most interesting perspective, however, seems to be the development of new BT preparations with improved specific potency and reduced antigenicity.