TOWER: design and results of an open-label incobotulinumtoxinA dose-titration study (up to 800U) in upper and lower limb spasticity
Prof Djamel BENSMAILa, Dr Nicolas ROCHEa, Prof Isabelle LAFFONTb, Dr Flavia COROIANb
a Hôpital Raymond-Poincaré (AP-HP), b CHU de Montpellier
Background: According to treatment guidelines in spasticity management, botulinum toxin injections should be offered as a treatment option for focal spasticity. In severe combined upper and lower limb or in multifocal spasticity, doses required to improve goal achievement and fulfill patients’ needs can result in total doses exceeding those currently approved, which are in France 360U for onabotulinumtoxinA 400U for incobotulinumtoxinA and 1500U for abobotulinumtoxinA. Therefore, the challenges of treating patients with multifocal spasticity with botulinum toxin type A increase with the number of disabling patterns. Physicians may need to prioritize treating patterns with a high impact on overall goal achievement.
Methods: TOWER is a prospective, open-label, non-randomized, single-arm, multicenter, dose-titration phase III study with the aim to investigate the safety and efficacy of incobotulinumtoxinA in the treatment of spasticity in patients who are deemed to require total body doses of up to 800U. The study employs a dose-titration approach over three injection cycles with a fixed total body dose of 400U of incobotulinumtoxinA for injection cycle 1, 600U for cycle 2 and 800U for cycle 3 with a maximum dose per limb of 400U in cycle 1 and 600U in cycle 2 and 3.
Results: 155 patients aged 18-80 years with spasticity of the upper and lower limb of the same body side due to cerebral causes and having to deemed by the investigator to require total body doses of incobotulinumtoxinA 800U during the course of the trial, participate at 30 study sites in Canada, France, Germany, Italy, Norway, Portugal, Spain, and the USA. Results of the cycle with 800U show that the number of patterns treated is higher with this cycle than at the cycle with 600U. The same results are found between the cycle with 600U and 400U.
Conclusion: Many physicians would like to be allowed greater dosing flexibility to improve treatment satisfaction for a subset of patients with post-stroke spasticity. Results from TOWER study show that the treated number of patterns is higher with this cycle than the cycle with 600U. The same results are found between the cycle with 600U and 400U.
Keywords : Botulinum toxin; multifocal spasticity; high doses; safety