Tags

Type your tag names separated by a space and hit enter

Botulinum toxin treatment of spasticity targeted to muscle endplates: an international, randomised, evaluator-blinded study comparing two different botulinum toxin injection strategies for the treatment of upper limb spasticity.
BMJ Open 2019; 9(5):e024340BO

Abstract

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.

Authors+Show Affiliations

Department of Neurology, Haukeland University Hospital, Bergen, Norway.Department of Neurology, Spasticity Clinic, Rigshospitalet Glostrup, Glostrup, Denmark.Department of Neurology, University Hospital of Copenhagen, Roskilde Sygehus, Denmark.Department of Neurology, Vejle Hospital, Vejle, Denmark.Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.Department of Rehabilitation Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.Medical department, Institut Produits Synthese (AB), Stockholm, Sweden.Medical department, Institut Produits Synthese (AB), Stockholm, Sweden.Medical department, Institut Produits Synthese (AB), Stockholm, Sweden.Medical department, Institut Produits Synthese (AB), Stockholm, Sweden. Ipsen Innovation, Ipsen, Les Ulis, France.Clinic of Dystonia, Bispjeberg Hospital, Copenhagen, Denmark.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31061021

Citation

Rekand, Tiina, et al. "Botulinum Toxin Treatment of Spasticity Targeted to Muscle Endplates: an International, Randomised, Evaluator-blinded Study Comparing Two Different Botulinum Toxin Injection Strategies for the Treatment of Upper Limb Spasticity." BMJ Open, vol. 9, no. 5, 2019, pp. e024340.
Rekand T, Biering-Sörensen B, He J, et al. Botulinum toxin treatment of spasticity targeted to muscle endplates: an international, randomised, evaluator-blinded study comparing two different botulinum toxin injection strategies for the treatment of upper limb spasticity. BMJ Open. 2019;9(5):e024340.
Rekand, T., Biering-Sörensen, B., He, J., Vilholm, O. J., Christensen, P. B., Ulfarsson, T., ... Dalager, T. (2019). Botulinum toxin treatment of spasticity targeted to muscle endplates: an international, randomised, evaluator-blinded study comparing two different botulinum toxin injection strategies for the treatment of upper limb spasticity. BMJ Open, 9(5), pp. e024340. doi:10.1136/bmjopen-2018-024340.
Rekand T, et al. Botulinum Toxin Treatment of Spasticity Targeted to Muscle Endplates: an International, Randomised, Evaluator-blinded Study Comparing Two Different Botulinum Toxin Injection Strategies for the Treatment of Upper Limb Spasticity. BMJ Open. 2019 May 5;9(5):e024340. PubMed PMID: 31061021.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Botulinum toxin treatment of spasticity targeted to muscle endplates: an international, randomised, evaluator-blinded study comparing two different botulinum toxin injection strategies for the treatment of upper limb spasticity. AU - Rekand,Tiina, AU - Biering-Sörensen,Bo, AU - He,Jun, AU - Vilholm,Ole Jakob, AU - Christensen,Peter Brøgger, AU - Ulfarsson,Trandur, AU - Belusa,Roger, AU - Ström,Torbjörn, AU - Myrenfors,Peter, AU - Maisonobe,Pascal, AU - Dalager,Torben, Y1 - 2019/05/05/ PY - 2019/5/8/entrez PY - 2019/5/8/pubmed PY - 2019/5/8/medline KW - abobotulinumtoxina KW - bont KW - botulinum toxin KW - neuromuscular junctions KW - nmj zone SP - e024340 EP - e024340 JF - BMJ open JO - BMJ Open VL - 9 IS - 5 N2 - 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. SN - 2044-6055 UR - https://www.unboundmedicine.com/medline/citation/31061021/Botulinum_toxin_treatment_of_spasticity_targeted_to_muscle_endplates:_an_international,_randomised,_evaluator-blinded_study_comparing_two_different_botulinum_toxin_injection_strategies_for_the_treatment_of_upper_limb_spasticity L2 - http://bmjopen.bmj.com/cgi/pmidlookup?view=long&pmid=31061021 DB - PRIME DP - Unbound Medicine ER -