Safety and efficacy of incobotulinumtoxinA doses up to 800 U in limb spasticity: The TOWER study.

Abstract

Objective:To evaluate safety (primary objective) and efficacy of increasing doses (400 U up to 800 U) of incobotulinumtoxinA (Xeomin, Merz Pharmaceuticals GmbH) for patients with limb spasticity.Methods:In this prospective, single-arm, dose-titration study (NCT01603459), patients (18–80 years) with spasticity due to cerebral causes, who were clinically deemed to require total doses of 800 U incobotulinumtoxinA, received 3 consecutive injection cycles (ICs) with 400 U, 600 U, and 600–800 U incobotulinumtoxinA, respectively, each followed by 12–16 weeks' observation. Outcomes included adverse events (AEs), antibody testing, Resistance to Passive Movement Scale (REPAS; based on the Ashworth Scale), and Goal Attainment Scale.Results:In total, 155 patients were enrolled. IncobotulinumtoxinA dose escalation did not lead to an increased incidence of treatment-related AEs (IC1: 4.5%; IC2: 5.3%; IC3: 2.9%). No treatment-related serious AEs occurred. The most frequent AEs overall were falls (7.7%), nasopharyngitis, arthralgia, and diarrhea (6.5% each). Five patients (3.2%) discontinued due to AEs. No patient developed secondary nonresponse due to neutralizing antibodies. Mean (SD) REPAS score improvements from each injection to 4 weeks postinjection increased throughout the study (IC1: −4.6 [3.9]; IC2: −5.9 [4.2]; IC3: −7.1 [4.8]; p < 0.0001 for all). The proportion of patients achieving ≥3 (of 4) treatment goals also increased (IC1: 25.2%; IC2: 50.7%; IC3: 68.6%).Conclusion:Escalating incobotulinumtoxinA doses (400 U up to 800 U) did not compromise safety or tolerability, enabled treatment in a greater number of muscles/spasticity patterns, and was associated with increased treatment efficacy, improved muscle tone, and goal attainment.ClinicalTrials.gov identifier:NCT01603459.Classification of evidence: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.