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.

Clinicaltrialsgov 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.

Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Figures

Figure 1. Study design

*If a dose of 800 U was not justified for clinical or safety reasons, a lower dose of 600–800 U could be administered as an exception. TC = telephone contact; V = visit.

Figure 2. Efficacy outcomes

(A) Each patient and health care team identified 2 realistic treatment goals per limb (1 active and 1 passive) at each injection visit. Goal attainment for each injection cycle was rated at the next injection visit or the end of study visit. (B) The proportions of patients with a rating of very good or good are shown. Possible ratings were 1 = very good, 2 = good, 3 = moderate, 4 = poor.