Extension Study to Assess the Safety and Efficacy of Repeated AbobotulinumtoxinA Injections in Adults with Upper Limb Spasticity

Objective: To assess long term safety and efficacy of abobotulinumtoxinA in hemiparetic patients with upper limb spasticity (ULS) post stroke/traumatic brain injury (TBI) over repeated treatment Background: Few studies have assessed long term safety and efficacy of repeated botulinum toxin injections in the treatment of adult spasticity. Methods: Phase III, multicentre, open-label extension including patients from a double-blind (DB) study (published) and de novo patients. Patients (18-78 years) received abobotulinumtoxinA 500U, 1000U or 1500U (per investigator’s judgement) for up to 4/5 cycles. Safety (primary objective) assessments consisted of monitoring treatment emergent adverse events (TEAEs), vital signs, laboratory and ECG. Efficacy assessments included muscle tone (Modified Ashworth Scale, MAS) in the primary targeted muscle group (PTMG), Physician Global Assessment (PGA) and Disability Assessment Scale (DAS) in the principal target of treatment (PTT) (primary/secondary endpoints in DB). Results for abobotulinumtoxinA, irrespective of dose administered (i.e. 500U/1000U/1500U combined), over cycles are presented. Results: Safety population comprised 258 patients (31 de novo). Incidence of TEAEs decreased with each cycle (41.6[percnt] [DB] to 13.6[percnt] [cycle 4, C4]). No clinically significant changes in haematology/biochemistry, vital signs and ECG occurred over cycles. Safety was comparable between doses. The percentage of MAS responders (≥1 grade reduction from baseline to Week 4) in PTMG was maintained at 75[percnt] from DB to C4. Mean (SD) PGA at Week 4 improved from 1.5 (1.0) in DB to 2.0 (0.9) at C4. The percentage of responders (≥1 grade reduction from baseline to Week 4) in DAS for the PTT also improved over cycles (55[percnt] [DB] to 74[percnt] [C4]). Conclusions: Safety analysis in this long term study did not generate any new unexpected safety findings; safety profile was similar across doses. Repeated abobotulinumtoxinA injections were associated with sustained or progressive improvement in muscle tone, perceived function (DAS) and global assessment in ULS patients post stroke/TBI.Supported by:Ipsen Disclosure: Dr. Brashear has received personal compensation for activities with Allergan, Ipsen, Revance and Concerta as a consultant. Dr. Brashear has received royalty payments from books royalties. Dr. Brashear has received research support from Ipsen, Merz, Allerg Dr. Marciniak has nothing to disclose. Dr. Edgley has received research support from Ipsen. Dr. Gul has received research support from FG as an investigator in an Ipsen trial. Dr. Hedera has nothing to disclose. Dr. McAllister has received personal compensation for activities with Teva CNS, Allergan, Mallinckrodt, Ipsen, Merz Pharmaceuticals, Depomed, Pfizer and XenoPort as a speaker. Dr. O9Dell has received research support from Ipsen. Dr. Rubin has received personal compensation for activities with Allergan and Merz as a speaker. Dr. Walker has received research support from Ipsen. Dr. Vilain has received personal compensation for activities with Ipsen Innovation as an employee. Dr. Mahmood has received personal compensation for activities with Ipsen as an employee. Dr. Gracies has received research support from Ipsen.