Prospective analysis of neutralising antibody titres in secondary non-responders under continuous treatment with a botulinumtoxin type A preparation free of complexing proteins—a single cohort 4-year follow-up study

OBJECTIVES: In long-term botulinum neurotoxin treatment, loss of therapeutic efficacy may occur due to neutralising antibody formation. Preliminary results with incobotulinumtoxinA, a preparation free of complexing/accessory proteins, have indicated a low antigenicity. We hypothesised that continuous treatment with this botulinum neurotoxin preparation would not result in an increase in neutralising antibody titres (NABTs) in patients with pre-existing NABTs. DESIGN: Prospective, blinded cohort study. SETTING: Single centre in Germany. PARTICIPANTS: Thirty-seven cervical dystonia patients with NABTs and partial secondary non-responsiveness to their previous botulinum neurotoxin type A treatment. INTERVENTION: Three-monthly intramuscular injections of incobotulinumtoxinA with a constant dose of 200 MU per injection during the first year; thereafter up to 500 MU for the next 36 months. OUTCOME MEASURES: Primary outcome measure: number of patients in whom NABTs declined below the initial titre after 48 months of incobotulinumtoxinA treatment or in whom titres had become negative within the 48 months. Secondary outcome measure: steepness of changes in NABT. NABTs were determined by mouse hemidiaphragm assay. Findings were compared to long-term data from 24 cervical dystonia patients who had developed NABTs and in whom treatment had been discontinued. RESULTS: Following a transient increase in the first 24 months under incobotulinumtoxinA treatment in some patients, NABTs declined well below the initial titre in the majority of patients. Test assay results were negative in most of the patients followed for more than 36 months. NABTs seemed to decline into the negative detection range as rapidly under incobotulinumtoxinA treatment as after cessation of botulinum neurotoxin therapy. CONCLUSIONS: The reduction of NABTs despite continuous treatment with incobotulinumtoxinA indicates low antigenicity of incobotulinumtoxinA. This might have implications on restrictions such as minimum injection intervals of ≥10 weeks currently in place for maintaining successful long-term application of botulinum neurotoxin.