Clinical Improvement After Treatment With IncobotulinumtoxinA (XEOMIN®) in Patients With Cervical Dystonia Resistant to Botulinum Toxin Preparations Containing Complexing Proteins.

This study investigated the clinical long-term effect of incobotulinumtoxinA (incoBoNT/A) in 33 cervical dystonia (CD) patients who had developed partial secondary therapy failure (PSTF) under previous long-term botulinum toxin (BoNT) treatment. Patients were treated four times every 12 weeks with incoBoNT/A injections. Physicians assessed treatment efficacy using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) at the baseline visit, week 12 and 48. Patients rated quality of life of CD with the Craniocervical Dystonia Questionnaire (CDQ-24). Titres of neutralizing antibodies(NAB) were determined at start of the study and after 48 weeks. All patients had experienced significant and progressive worsening of symptoms in the last 6 months of previous BoNT treatment. Repeated incoBoNT/A injections resulted in a significant reduction in mean TWSTRS at week 12 and 48. Patients' rating of quality of life was highly correlated with TWSTRS but did not change significantly over 48 weeks. During the 48 weeks -period of incoBoNT/A treatment NAB titres decreased in 32.2%, did not change in 45.2%, and only increased in 22.6% of the patients. Thus, repeated treatment with the low dose of 200 MU incoBoNT/A over 48 weeks provided a beneficial clinical long-term effect in PSTF and did not booster titres of NAB.

Long-term adherence and response to botulinum toxin in different indications.

OBJECTIVE: The objective of the study was the analysis of adherence and self-perceived treatment response to long-term botulinum neurotoxin type A (BoNT-A) treatment in different neurological indications. METHODS: In this retrospective, monocentric, observational study, cross-sectional and longitudinal data of 1351 patients documenting 20705 injection appointments at the BoNT outpatient clinic of Heinrich Heine University Duesseldorf between 1989 and 2014 were retrospectively analyzed. Patients had been treated with BoNT for neurological conditions, including cervical dystonia (CD), blepharospasm (BSP), other dystonia (ODT), hemifacial spasm (HFS), and spasticity (SPAS). The parameters longitudinally analyzed for the entire cohort were therapy duration as well as the mean and cumulative BoNT-A dose. Cross-sectionally, for subgroups of at least 721, patients' global self-perceived quality of health and life, global self-perceived reduction of symptoms by BoNT-A treatment as well as the clinical global impression were evaluated. Furthermore, mouse hemidiaphragm assay antibodies (MHDA-ABs) were analyzed in a subgroup. RESULTS: The mean treatment duration was 4.58 years (95% CI 4.32-4.84), and 678 (50.2%) therapy dropouts of 1351 patients occurred within the first 8 years. Therapy adherence and self-perceived symptom reduction in long-term BoNT-A treatment over the years were significantly longer in BSP, HFS, and CD patients than in ODT and SPAS patients. INTERPRETATION: The treatment indication determines long-term adherence and self-perceived symptom reduction in BoNT-A therapy, which are better in BSP, HFS, and CD patients than in ODT and SPAS patients. MHDA-ABs had a significant impact on global self-perceived symptom reduction, but with only a limited degree.

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. 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.