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Efficacy and Safety of Repeated Incobotulinumtoxina Injections for Upper-Limb Post-Stroke Spasticity
e10 improvement. Subgroup analysis was completed on three TPO categories (i.e., acute, post-acute, chronic) in a repeated measures ANCOVA to determine the ability to make/maintain gains. Models controlled for age, admission Functional Independence Measure (FIM) score, and therapy intensity. Main Outcome Measure(s): FIM and Stroke Impact Scale (SIS). Results: In total, 1,416 individuals (53.5% male, mean age 70.013.2 years) accessed the CSRT program and received active therapy (4 visits). Regression analyses revealed no significant impact of TPO on any of the outcome variables. However, with each additional week post onset, the ability to make gains during CSRT service decreased in the FIM, SIS #1 (Physical Strength), #5 (ADLs) & #6 (Mobility). In subgroup analyses, all groups improved significantly on the FIM and SIS and maintained these gains at follow up. Conclusions: TPO was not shown to be a significant predictor of the ability of individuals to make gains within the CSRT program. This study supports that individuals would benefit from ongoing rehabilitation services throughout their stroke recovery process. Key Words: Stroke, Outpatient, Home-based rehabilitation Disclosures: None disclosed.
Oral Presentation 450 Safety and Efficacy of Increasing Doses of IncobotulinumtoxinA (400U-800U) for Upper and Lower Limb Spasticity: The Phase III TOWER Study John McGuire (Medical College of Wisconsin), Jo¨rg Wissel, Djamel Bensmail, Astrid Scheschonka, Olivier Simon, David M. Simpson Research Objectives: Patients with severe multifocal spasticity may benefit from botulinum toxin treatment at higher doses. This study evaluated the safety and efficacy of increasing incobotulinumtoxinA doses (400U-800U) for patients with spasticity. Design: Prospective, single-arm, dose-titration study (NCT01603459). Setting: Thirty sites in 8 countries (Norway, Germany, Spain, Italy, France, Portugal, Canada, and the United States). Participants: Adult patients (aged 18-80 years) with spastic hemiparesis due to cerebral causes. Interventions: Patients received 3 consecutive injection cycles (ICs) with 400U, 600U, and 600-800U incobotulinumtoxinA, respectively, each followed by 12-16 weeks of observation. Main Outcome Measure(s): Outcome measures included adverse events (AEs), Resistance to Passive Movement Scale (REPAS, based on the Ashworth Scale), Goal Attainment Scale, and EuroQoL 5-dimensions (EQ-5D) questionnaire. Results: In total, 155 patients were enrolled. IncobotulinumtoxinA dose escalation did not lead to an increased incidence of AEs (IC1:36.1%; IC2:37.5%; IC3:25.7%). The most frequent AEs were falls (7.7%), nasopharyngitis, arthralgia, and diarrhea (6.5% each). No treatment-related serious AEs occurred; 5 patients (3.2%) discontinued due to AEs. The mean (standard deviation [SD]) change in REPAS score from each injection to 4 weeks post-injection 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 out of 4 treatment goals increased throughout the study (IC1: 25.2%; IC2: 50.7%; IC3: 68.6%). Mean (SD) EQ-5D QoL scores improved from 59.9 (18.9) at baseline to 69.7 (17.6) at the end of study visit (P<0.0001). Conclusions: Increasing incobotulinumtoxinA doses (400U up to 800U) enabled treatment in a greater number of muscles, leading to increased treatment efficacy resulting in improved muscle tone, individual goal attainment, and quality of life, without compromising patients’ safety or tolerability. Key Words: Muscle spasticity, Botulinum Toxin Type A, IncobotulinumtoxinA Disclosures: John McGuire, Jo¨rg Wissel, Djamel Bensmail, and David M. Simpson received support as investigators from Merz. Astrid Scheschonka and Olivier Simon are employees of Merz.
Oral Research Presentations Oral Presentation 459 Efficacy and Safety of Repeated Incobotulinumtoxina Injections for Upper-Limb Post-Stroke Spasticity Christina Marciniak (Rehabilitation Institute of Chicago), Atul T. Patel, Michael C. Munin, Angelika Hanschmann, Reinhard Hiersemenzel, Elie P. Elovic Research Objectives: To investigate efficacy and safety of repeated incobotulinumtoxinA injections for upper-limb post-stroke spasticity. Design: A 36-week open-label extension (OLEX) of the randomized, doubleblind, placebo-controlled main period of a phase III trial (NCT01392300). Setting: Forty-six sites in seven countries (the Czech Republic, Germany, Hungary, India, Poland, Russia, and the United States). Participants: Subjects (aged 18e80 years) with upper-limb post-stroke spasticity, who completed the 12-week main period of the phase 3 trial. Interventions: Subjects received 3 incobotulinumtoxinA treatments (400U), injected into the affected muscles of one upper-limb at fixed 12-week intervals. Main Outcome Measure(s): Outcome measures included: evaluation of muscle tone (Ashworth Scale (AS); Disability Assessment Scale (DAS); Carer Burden Scale; and incidence of adverse events (AEs). Results: In total, 248 subjects completed the OLEX. Proportions of subjects with 1 point improvement in AS score in each cycle ranged from 52.3%e 59.2% for wrist flexors, 49.1%e52.3% for elbow flexors, 59.8%e64.5% for finger flexors, 35.5%e41.2% for thumb flexors, and 37.4%e39.9% for forearm pronators (P<0.0001 for all). The mean DAS score for the principal target domain significantly improved from each incobotulinumtoxinA treatment to the respective 4-week assessment (P<0.0001 for all). Significant improvements in Carer Burden Scale scores were observed for cleaning palm, cutting fingernails, and putting arm through sleeve (P<0.0001 for all). Treatmentrelated AEs were reported by 9/296 subjects (3.0%), most frequently pain in the extremity (nZ2, 0.7%) and constipation (nZ2, 0.7%). Serious AEs were reported by 22 subjects (7.4%); none were treatment-related. Conclusions: Repeated incobotulinumtoxinA treatment was well-tolerated, significantly reduced upper-limb spasticity, and led to significant improvements in muscle tone that translated into meaningful clinical improvements in disability and carer burden. Key Words: Muscle spasticity, Botulinum Toxin Type A, IncobotulinumtoxinA Disclosures: Christina Marciniak, Michael Munin, and Elie Elovic have received support as investigators for Merz. Angelika Hanschmann and Reinhard Hiersemenzel are employees of Merz.
Oral Presentation 464 Randomized, Placebo-Controlled, Phase III Study of Incobotulinumtoxina for Upper-Limb Post-Stroke Spasticity Atul Patel (Kansas City Bone and Joint Clinic), Christina Marciniak, Michael C. Munin, Angelika Hanschmann, Reinhard Hiersemenzel, Elie P. Elovic Research Objectives: To study efficacy and safety of incobotulinumtoxinA for upper-limb post-stroke spasticity. Design: Prospective, multicenter, randomized, double-blind, placebocontrolled, parallel-group study evaluated subjects over 12-weeks following a single treatment of incobotulinumtoxinA (400U) or placebo. Setting: Forty-six sites in seven countries (the Czech Republic, Germany, Hungary, India, Poland, Russia, and the United States). Participants: Subjects (aged 18e80 years) with upper-limb post-stroke spasticity and a flexed elbow, flexed wrist and clenched fist clinical pattern of spasticity with a muscle tone of 2 on Ashworth Scale (AS) at each site were eligible to enroll. Interventions: Investigators treated the primary target clinical pattern (PTCP) with a fixed dose (flexed elbow: 200U, flexed wrist: 150U, clenched fist: 100U). Doses for other muscles were flexible.
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Oral Presentation 450 Safety and Efficacy of Increasing Doses of IncobotulinumtoxinA (400U-800U) for Upper and Lower Limb Spasticity: The Phase III TOWER Study John McGuire (Medical College of Wisconsin), Jo¨rg Wissel, Djamel Bensmail, Astrid Scheschonka, Olivier Simon, David M. Simpson Research Objectives: Patients with severe multifocal spasticity may benefit from botulinum toxin treatment at higher doses. This study evaluated the safety and efficacy of increasing incobotulinumtoxinA doses (400U-800U) for patients with spasticity. Design: Prospective, single-arm, dose-titration study (NCT01603459). Setting: Thirty sites in 8 countries (Norway, Germany, Spain, Italy, France, Portugal, Canada, and the United States). Participants: Adult patients (aged 18-80 years) with spastic hemiparesis due to cerebral causes. Interventions: Patients received 3 consecutive injection cycles (ICs) with 400U, 600U, and 600-800U incobotulinumtoxinA, respectively, each followed by 12-16 weeks of observation. Main Outcome Measure(s): Outcome measures included adverse events (AEs), Resistance to Passive Movement Scale (REPAS, based on the Ashworth Scale), Goal Attainment Scale, and EuroQoL 5-dimensions (EQ-5D) questionnaire. Results: In total, 155 patients were enrolled. IncobotulinumtoxinA dose escalation did not lead to an increased incidence of AEs (IC1:36.1%; IC2:37.5%; IC3:25.7%). The most frequent AEs were falls (7.7%), nasopharyngitis, arthralgia, and diarrhea (6.5% each). No treatment-related serious AEs occurred; 5 patients (3.2%) discontinued due to AEs. The mean (standard deviation [SD]) change in REPAS score from each injection to 4 weeks post-injection 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 out of 4 treatment goals increased throughout the study (IC1: 25.2%; IC2: 50.7%; IC3: 68.6%). Mean (SD) EQ-5D QoL scores improved from 59.9 (18.9) at baseline to 69.7 (17.6) at the end of study visit (P<0.0001). Conclusions: Increasing incobotulinumtoxinA doses (400U up to 800U) enabled treatment in a greater number of muscles, leading to increased treatment efficacy resulting in improved muscle tone, individual goal attainment, and quality of life, without compromising patients’ safety or tolerability. Key Words: Muscle spasticity, Botulinum Toxin Type A, IncobotulinumtoxinA Disclosures: John McGuire, Jo¨rg Wissel, Djamel Bensmail, and David M. Simpson received support as investigators from Merz. Astrid Scheschonka and Olivier Simon are employees of Merz.
Oral Research Presentations Oral Presentation 459 Efficacy and Safety of Repeated Incobotulinumtoxina Injections for Upper-Limb Post-Stroke Spasticity Christina Marciniak (Rehabilitation Institute of Chicago), Atul T. Patel, Michael C. Munin, Angelika Hanschmann, Reinhard Hiersemenzel, Elie P. Elovic Research Objectives: To investigate efficacy and safety of repeated incobotulinumtoxinA injections for upper-limb post-stroke spasticity. Design: A 36-week open-label extension (OLEX) of the randomized, doubleblind, placebo-controlled main period of a phase III trial (NCT01392300). Setting: Forty-six sites in seven countries (the Czech Republic, Germany, Hungary, India, Poland, Russia, and the United States). Participants: Subjects (aged 18e80 years) with upper-limb post-stroke spasticity, who completed the 12-week main period of the phase 3 trial. Interventions: Subjects received 3 incobotulinumtoxinA treatments (400U), injected into the affected muscles of one upper-limb at fixed 12-week intervals. Main Outcome Measure(s): Outcome measures included: evaluation of muscle tone (Ashworth Scale (AS); Disability Assessment Scale (DAS); Carer Burden Scale; and incidence of adverse events (AEs). Results: In total, 248 subjects completed the OLEX. Proportions of subjects with 1 point improvement in AS score in each cycle ranged from 52.3%e 59.2% for wrist flexors, 49.1%e52.3% for elbow flexors, 59.8%e64.5% for finger flexors, 35.5%e41.2% for thumb flexors, and 37.4%e39.9% for forearm pronators (P<0.0001 for all). The mean DAS score for the principal target domain significantly improved from each incobotulinumtoxinA treatment to the respective 4-week assessment (P<0.0001 for all). Significant improvements in Carer Burden Scale scores were observed for cleaning palm, cutting fingernails, and putting arm through sleeve (P<0.0001 for all). Treatmentrelated AEs were reported by 9/296 subjects (3.0%), most frequently pain in the extremity (nZ2, 0.7%) and constipation (nZ2, 0.7%). Serious AEs were reported by 22 subjects (7.4%); none were treatment-related. Conclusions: Repeated incobotulinumtoxinA treatment was well-tolerated, significantly reduced upper-limb spasticity, and led to significant improvements in muscle tone that translated into meaningful clinical improvements in disability and carer burden. Key Words: Muscle spasticity, Botulinum Toxin Type A, IncobotulinumtoxinA Disclosures: Christina Marciniak, Michael Munin, and Elie Elovic have received support as investigators for Merz. Angelika Hanschmann and Reinhard Hiersemenzel are employees of Merz.
Oral Presentation 464 Randomized, Placebo-Controlled, Phase III Study of Incobotulinumtoxina for Upper-Limb Post-Stroke Spasticity Atul Patel (Kansas City Bone and Joint Clinic), Christina Marciniak, Michael C. Munin, Angelika Hanschmann, Reinhard Hiersemenzel, Elie P. Elovic Research Objectives: To study efficacy and safety of incobotulinumtoxinA for upper-limb post-stroke spasticity. Design: Prospective, multicenter, randomized, double-blind, placebocontrolled, parallel-group study evaluated subjects over 12-weeks following a single treatment of incobotulinumtoxinA (400U) or placebo. Setting: Forty-six sites in seven countries (the Czech Republic, Germany, Hungary, India, Poland, Russia, and the United States). Participants: Subjects (aged 18e80 years) with upper-limb post-stroke spasticity and a flexed elbow, flexed wrist and clenched fist clinical pattern of spasticity with a muscle tone of 2 on Ashworth Scale (AS) at each site were eligible to enroll. Interventions: Investigators treated the primary target clinical pattern (PTCP) with a fixed dose (flexed elbow: 200U, flexed wrist: 150U, clenched fist: 100U). Doses for other muscles were flexible.
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