Revues et méta-analyses SRBMPR / SOFMER

Le 14/10/2021 de 16:30 à 18:00

Retour Session


Efficacité dose-réponse et durée d'efficacité de la toxine botulique dans la spasticité post-AVC chez l'adulte : revue systématique et méta-analyse basée sur un modèle.

Etienne Ojardias (Saint-Etienne, France), Edouard Ollier (Saint-Etienne, France), Ludovic Lafaie (Saint-Etienne, France), Thomas Celarier (Saint-Etienne, France), Pascal Giraux (Saint-Étienne, France), Laurent Bertoletti (Saint-Etienne, France)

Objective : Few data provide a comparative description of the dose-response, time course effect and relationship between dose and safety for all Botulinum toxin (BoNT).

Material / Patients and Methods : We conducted a systematic review in Medline, PeDro and Google Scholar databases up to March 2020. We selected randomized, controlled trials in post-stroke patients with arm or leg muscle hypertonia, comparing BoNT to placebo. The main outcome was based on Modified Ashworth Scale (MAS) score. A non-linear mixed effect model was used to estimate maximal toxin and placebo effects (Emax and Eplacebo), the effect disappearance half-life (T1/2 off) of BoNT and the doses achieving 50% and 80% of Emax (D50 and D80). The equivalence ratios between different BoNT were calculated from D50 values. Adverse events were recorded.

Results : A total of 2,236 unique records were screened. Thirty-five eligible trials were identified, including 2,692 patients. The BoNT Emax was -1.11 (-1.33; -0.89) was reached at 5 weeks for all BoNT. A maximal placebo effect was estimated at -0.28 (-0.36; -0.20). Compared to OnabotulinumtoxinA at D50, the equivalence ratio was significantly higher for AbobotulinumtoxinA (3.35) and lower for LetibotulinumtoxinA (0.40). T1/2 off was longer for AbobotulinumtoxinA, 10 weeks (5.6; 15.2), than for OnabotulinumtoxinA and the other BoNT, 6.7 (4.8; 8.5) weeks. Adverse events were minor.

Discussion - Conclusion : This first pharmacodynamic model-based meta-analysis supports a common maximal effect on MAS score at 4-5 weeks for all the different BoNT preparation on muscle tone but also revealed significant differences in effect duration. Differences between certain BoNT unit scales were also confirmed.

Keywords : Botulinum toxins; stroke; muscle spasticity; muscle tone; meta-analysis; model-based; dose response; time course

Disclosure of interest : Pascal Giraux and Etienne Ojardias received meeting sponsorship from Allergan, Ipsen, and Merz, and received compensations for consulting from Merz. Etienne Ojardias received through his institution a research support grant from Merz. Pascal Giraux is a co-founder of the Dessintey company. The other authors declare no conflict of interest. All the authors agreed to the submission of the final manuscript. This research was not supported by any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.