TOWER: Design and results of an open-label incobotulinumtoxinA dose-titration study (up to 800 U) in upper and lower limb spasticity

Abstract

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 fulfil patients’ needs can result in total doses exceeding those currently approved, which are in France 360 U for onabotulinumtoxin A 400 U for incobotulinumtoxin A and 1500 U for abobotulinumtoxin A. 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. 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 800 U. The study employs a dose-titration approach over three injection cycles with a fixed total body dose of 400 U of incobotulinumtoxinA for injection cycle 1, 600 U for cycle 2 and 800 U for cycle 3 with a maximum dose per limb of 400 U in cycle 1 and 600 U in cycle 2 and 3. One hundred and fifty-five 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 800 U 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 800 U show that the number of patterns treated is higher with this cycle than at the cycle with 600 U. The same results are found between the cycle with 600 U and 400 U. 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 600 U. The same results are found between the cycle with 600 U and 400 U.