Objectives The therapeutic effects of botulinum neurotoxin (BoNT) are well documented in upper limb spasticity. However, several factors may influence treatment efficacy, including targeting of neuromuscular junctions (NMJs). We examined whether NMJ-targeted BoNT injections were non-inferior, in terms of efficacy, to current injection practices.
Design Open-label prospective evaluator-blinded study.
Setting Conducted across 20 medical centres in Denmark, Finland, Norway and Sweden (24 September 2012 to 11 March 2015).
Participants Aged ˃18 years with upper limb spasticity (Modified Ashworth Scale [MAS] score of 2 or 3) following stroke or traumatic brain injury, had received ≥2 consecutive BoNT-A treatment cycles (the latest of which was abobotulinumtoxinA [aboBoNT-A]) and needed BoNT-A retreatment (same modality as previous cycle). Patients requiring aboBoNT-A doses >800units were excluded. In total, 88 patients were randomised (intention-to-treat [ITT] population), most were male (n=58/88, 65.9%) and 54/88 (61.4%) completed the study (per protocol [PP] population).
Interventions Randomisation (1:1) to receive a single dose of aboBoNT-A (≤800 U) according to either current clinical practice (300 U/mL) or as an NMJ-targeted injection (100 U/mL).
Primary outcome measure Proportion of patients with a ≥1 level reduction from baseline in MAS score at week 4 post-injection (responders).
Results In the ITT population, the proportion of responders at elbow flexors was 72.7% in the current practice group and 56.8% in the NMJ-targeted group (adjusted difference −0.1673 [95% CIs: −0.3630 to 0.0284]; p=0.0986). Similar results were observed in the PP population (69.0% vs 68.0%, respectively, adjusted difference 0.0707 [−0.1948 to 0.3362]; p=0.6052).
Conclusions Owing to the limited number of participants, non-inferiority of NMJ-targeted injections could not be determined. However, there was no statistical difference between groups. Larger studies are needed confirm whether the two techniques offer comparable efficacy.
Trial registration number NCT01682148.
- botulinum toxin
- neuromuscular junctions
- nmj zone
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Contributors TR and BB-S performed the experiments, analysed the data and wrote the paper. TU and TD conceived and designed the experiments, performed the experiments and analysed the data. RB conceived and designed the experiments, analysed the data and wrote the paper. JH, OJV and PBC performed the experiments. TS conceived and designed the experiments, analysed the data. PM analysed the data. PM conceived and designed the experiments, analysed the data and contributed analysis tools.
Funding The study was sponsored by Ipsen.
Competing interests The authors have, during the last 3 years, received educational support from the sponsor, Ipsen AB and/or served as consultants for the sponsor. The sponsor contributed to the design of the study; in the collection, analyses/interpretation of data; in the writing of the manuscript and in the decision to publish the results.
Ethics approval The study received ethical approval from the committee for Scientific Etichs (De videnskapetiske Komiteer for Region Hovedstaden) Kongens Vænge 2, 3400 Hilleröd, Denmark (21 February 2012, 20 June 2012 and 04 July 2014); Central Finland Hospital District, Ethical Commission (Keski-Suomen sairaanhoitopiiri, Eettinen toimikunta), Sairaanhoitopiirin toimisto Rak. 6/2, Keskussairaalantie 19, 40620 Jyväskylä, Finland (27 January 2012 and 27 August 2012); the regional Ethics Committee in Stockholm (Regionala Etikprövningsnämnden i Stockholm), FE289, 171 77 Stockholm, Sweden (01 February 2012, 20 June 2012 and 04 July 2014) and the Regional Committee for Medical and Health Ethics south east Norway (Regional komité for medisinsk og, helsefaglig forskningsetikk REK, sør-øst- Norge), PO-box 1130, 0318 Oslo, Norway (07 August 2012, 01 November 2012 and 04 July 2014). The study was registered on clinicaltrials.gov on 12 September 2012 (NCT01682148).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Trial data analysed during the reported study are available to qualified researchers. Reasonable requests should be directed to the corresponding author.
Patient consent for publication Not required.