Development of resistance to botulinum toxin type A in patients with torticollis

Abstract

Between 1984 and 1992, 559 patients with torticollis were treated with botulinum toxin type A (btx) injections. Twenty-four of these 559 patients (4.3%) had serological evidence of antibodies to btx by mouse neutralization assay. Some of the 559 patients had only one or two injection series, whereas others were lost to follow-up, so that the actual prevalence of serologically detectable antibodies may be higher than 4%. In addition, some patients who improved after btx injections lost benefit and stopped developing muscle atrophy from adequate doses of btx, without serological evidence of antibodies. To evaluate the risk factors for btx resistance (loss of benefit and muscle atrophy after injections with or without serological evidence of antibodies), we reviewed the records of a cohort of torticollis patients injected over 2-45 months (mean, 23 months) beginning in 1988. Eight of 76 patients (10.5%) developed btx resistance. Compared to nonresistant patients from the same cohort, these eight patients received more frequent injections, had more "booster injections" 2-3 weeks after an initial injection, and received higher doses of btx per treatment. In order to minimize the risk of developing btx resistance, therefore, we recommend that physicians wait as long as possible (at least 1 month) between btx injections, avoid booster injections, and use the smallest possible doses.

Long-term efficacy of botulinum toxin A for treatment of blepharospasm, hemifacial spasm, and spastic entropion: a multicentre study using two drug-dose escalation indexes

“…39,45,59 The clinical reestablishment of muscle function after BoNT-A injections requires repeated injections over long periods. 49,50 The onset of resistance to botulinum toxin over time may be due to the immunological properties of the toxin that lead to the stimulation of antibody production, thus rendering further treatments ineffective. [48][49][50][51] Greene and Fahn 49 found that patients resistant to botulinum toxin received more booster injections early after treatment, as well as higher doses compared with responsive patients.…”

“…49,50 The onset of resistance to botulinum toxin over time may be due to the immunological properties of the toxin that lead to the stimulation of antibody production, thus rendering further treatments ineffective. [48][49][50][51] Greene and Fahn 49 found that patients resistant to botulinum toxin received more booster injections early after treatment, as well as higher doses compared with responsive patients. These authors, therefore, recommended that the lowest possible effective dose should be used, with treatment intervals of at least 3 months, and that booster injections be avoided.…”

“…48 Two recent reports suggest that higher doses and long-term use with shorter duration between treatments increase the risk of antibody formation and treatment failure. 49,50 Recently, two studies also confirmed that higher doses of BoNT-A than recommended (50 U Â eye) may be needed for some patients. 51,52 Therefore, it is important to determine whether efficacy with high-dose therapy can be sustained for long treatment periods without developing resistance, and whether the risk of complications is increased.…”

Poststroke Spasticity Management

“…It is unclear where the common practice of administering BoNT not more frequently than every 3 months was based, because the early studies of immunoresistance were in the cervical dystonia, not stroke, population. 43 Although no prospective investigation of antibody formation to repeated BoNT injection has been reported, it is estimated that the incidence of antibody to BoNT in the spastic hypertonia population is <1%, which is lower than in cervical dystonia. 44 Repeated BONT injections appear to result in sustained reduction of spastic hypertonia.…”

Botulinum Toxin and Other New Approaches to Migraine Therapy

“…Using an older formulation, it was estimated to occur in at least 5%-10% of patients with cervical dystonia (11). Factors that increase the risk for antibody formation include higher doses and short intervals between doses (12)(13)(14). With the new formulation and the relatively low doses used in migraine treatment (see below), this complication is unlikely to occur.…”