The TOWER study was a prospective, nonrandomized, single-arm, multicenter, open-label, dose-titration study. The primary objective was to investigate safety through assessments of adverse events (AEs) and investigators' global assessment of tolerability. Key efficacy data (muscle tone and resistance to passive movement scale [REPAS]; Goal Attainment Scale [GAS]; investigators' and patients' global assessment of efficacy) are also presented here. This study provides Class IV evidence that, for patients with limb spasticity, escalating incobotulinumtoxinA doses (400 U up to 800 U) increases treatment efficacy without compromising safety or tolerability because patients served as their own controls. The safety and efficacy findings from injection cycle 1, when all patients received treatment at the highest approved dose (400 U), were compared with those of cycles 2 and 3, when higher than labeled doses were administered. In addition, in the absence of a placebo control, all AEs had to be attributed to the drug, a bias against incobotulinumtoxinA. Due to word count limitations, additional efficacy data (including Disability Assessment Scale, Functional Ambulation Classification, and quality of life) will be reported separately.
The study comprised 3 injection cycles with escalating fixed total body doses of incobotulinumtoxinA (50 U/mL in normal saline) injected in the same body side (figure 1):

400 U into the upper limb only, the lower limb only, or both

600 U into the upper limb only, the lower limb only, or both

800 U into both the upper and the lower limbs (maximum dose 600 U per limb)

If a dose of 800 U incobotulinumtoxinA was clinically not indicated or in the case of safety concerns, a lower dose (≥600 U) could be administered as an exception in cycle 3. Individual doses for each clinical pattern were flexible within the range usually recommended/used/approved (table e-1 at Neurology.org). Patients were aware that they would receive 3 different doses during the study, but they did not know which dose they would receive at each visit.
Each treatment was followed by a 12- to 16-week observation period with telephone contacts at days 7 and 14, and clinic visits at weeks 4, 8, and 12–16 posttreatment to evaluate safety and efficacy. The planned regular duration of treatment was 36–48 weeks.