Introduction and objective: Up to 40% of stroke survivors will develop spasticity that may affect their ability to walk or cause other issues such as pain. The aim of this observational study was to assess longitudinal goal attainment with repeated injections of abobotulinumtoxinA (aboBoNT-A) for the management of leg spasticity in a routine clinical setting. Methods: AboliSh was a 16-month observational study (NCT04050527) that followed ambulatory adults (≥18 years able to take ≥5 steps with/without assistance) with unilateral leg spasticity who were treated with aboBoNT-A according to local clinical guidelines to achieve personalized treatment goals. Post-hoc analyses of cumulative goal attainment (assessed using GAS-leg across all treatment cycles) were performed for stroke survivors who underwent ≥1 BoNT-A injection cycle and had ≥1 GAS assessment (n=328). Potential predictors of response during Cycle 1 (defined as achieving a GAS T score of ≥50 during Cycle 1) were analyzed using a stepwise multivariate logistic regression model. We subsequently performed subgroup analyses for cumulated GAS T scores, categorized by age. Results: At Cycle 1, the median total injected dose of aboBoNT-A for the lower limb was 600U [range 100-1500U], which was injected into a median of 4 muscles [1-8]. Overall, 64% of study participants also required injections for upper limb spasticity; in these cases the median total body dose was 1362.5 U. At the population level, goals were achieved as expected over repeated cycles. The mean [95% CI] cumulated GAS-leg T score at 16 months was 48.2 [47.5, 49.0] (median of 50). Change in cumulated GAS T scores were clinically relevant; the mean change in GAS-leg score was 9.9 [9.1, 10.7] (median of 10). While age was found to be a significant prognostic factor in GAS-T response in Cycle 1 (p=0.03); mean±SD [median] cumulated GAS T scores were similar in the age subgroups of <50y: 49.4±7.1 [50] (n=103); 50-60y: 47.7±7.5 [50] (n=96); and >60y: 47.7±6.8 [50] (n=129). Conclusions: Results from this prospective, longitudinal study demonstrate the sustained functional benefit of repeated cycles of aboBoNT-A, as assessed by person-centered goal attainment.

Abstract Background and aims The EPITOME study (NCT06055725) evaluates how many stroke survivors with paresis develop post-stroke spasticity (PSS) that may benefit from medication within one-year. The study uses the 13-item Post-Stroke Spasticity Monitoring Questionnaire (PSMQ) for remote monitoring. This prespecified interim analysis measured predictiveness of PSMQ for spasticity detection. Methods Participants (18-85y) were recruited ≤4 weeks after first-ever stroke with paresis ≤2 weeks and completed the PSMQ at defined intervals. Participants whose PSMQ indicates possible spasticity (score ≥2) undergo a confirmatory assessment but continue monitoring if PSS is not clinically confirmed. For this analysis of the first 151 participants to reach month 3, all attended a clinic visit regardless of PSMQ score. Receiver operating characteristic (ROC) curve analyses evaluated which PSMQ items were most predictive of spasticity. Results PSMQ total scores remained low [median 0-1] throughout the first three months of follow-up. Overall 65.6% (99/151) had a PSMQ score of ≥2, and 45.7% (69/151) had confirmed PSS. The sensitivity of the PSMQ was 81% but specificity was 48%. ROCAUCanalysis revealed item predictiveness: Q1(stiffness/tightness) and Q2(difficulty bending/flexing limb): 0.66; Q6(symptoms >1 month): 0.61. Other items had an ROCAUC of ≤0.60. Simplifying the PMSQ to Q1 and Q2 retained tool predictiveness (ROCAUC of 0.69 with items 1+2 vs 0.66 with PSMQ-total score) while reducing the burden of questionnaire completion. Conclusions 45.7% of stroke survivors with paresis developed PSS within 3 months. A simplified tool using PMSQ Q1+Q2 will be used in the study to improve monitoring while reducing patient burden. Conflict of interest Richard D. Zorowitz, Laura Serrano Barrenechea, Simon Butet, David Hernández Herrero, Rama Prasad, and Alessandro Picelli are investigators for the EPITOME study, sponsored by Ipsen. Pascal Lecomte and Sophie Vandenbremt act as patient and caregiver advisors for Ipsen. Mathieu Beneteau, Pascal Maisonobe, and Simon Page are employed by Ipsen. Figure 1 - belongs to Results

Lack of head-to-head comparative safety and efficacy data for abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) represented an important gap for informed spasticity management. This study compared the safety and efficacy of aboBoNT-A and onaBoNT-A for upper limb spasticity (ULS). DIRECTION (NCT04936542), a phase IV, randomized, double-blind, crossover study, involved 72 sites. Patients stratified by botulinum toxin A status (naïve/non-naïve) were randomized (1:1) to aboBoNT-A 900U followed by onaBoNT-A 360U (one cycle each), or vice versa. Muscles (wrist/finger flexors, biceps brachii) were injected with a fixed volume, using instrument-guided injection techniques. Participants fulfilling retreatment criteria received a second cycle at Week 12; otherwise, they were reassessed every 4 weeks (to Week 24) until requiring retreatment. Primary analyses tested non-inferiority based on treatment-emergent adverse events (TEAEs) from injection to Week 12 using a 5 Spasticity of the upper limb presents as muscle and limb stiffness that affects the arm and/or hand. It happens when parts of the brain or spinal cord that control movement are damaged. Spasticity can be painful and can make daily activities challenging. Some people with upper limb spasticity receive botulinum toxin A (BoNT-A) injections to help relax the affected muscles. BoNT-A injections work for a period, but retreatment is required when the effects start to wear off. AbobotulinumtoxinA and onabotulinumtoxinA are different types of BoNT-A. DIRECTION is the first-ever spasticity study to compare abobotulinumtoxinA and onabotulinumtoxinA directly in people with upper limb spasticity. It involved 464 people living with spasticity across the USA, France, and Canada. The study population had an average age of 57 years, two-thirds were male, and most had spasticity because of a stroke. The study found that, over the 12 weeks after BoNT-A treatment, similar numbers of patients had side-effects to abobotulinumtoxinA and onabotulinumtoxinA. In addition, it took longer for symptoms to return after treatment with abobotulinumtoxinA (99 days) compared with onabotulinumtoxinA (96 days). Longer BoNT-A treatment duration can reduce the number of days that people with upper limb spasticity have to live with symptoms before their next injection. More symptom-free days could reduce the need for patients and their caregivers to seek additional care and could reduce their overall treatment burden. These findings provide new information to help healthcare professionals make decisions about BoNT-A treatment to achieve the best outcomes for their patients with arm/hand spasticity.

Objective: This post-hoc analysis evaluated how goal attainment evolved over repeated cycles of botulinum toxin A (BoNT-A) treatment in adults with upper-limb spasticity. Methods: ULIS-III (NCT02454803) was a 2-year observational study involving adults treated with BoNT-A. The analysis included 538 patients who received ≥ 4 BoNT-A injection cycles and had Goal Attainment Scaling (GAS) assessments for each of the first 4 cycles. GAS T-scores were used to measure treatment response. Multivariate models assessed predictors of achieving a GAS T-score ≥ 50 and being in the top tertile (best) of responders. Results: Patients generally maintained consistent goal domains across cycles. Mean change in GAS T-scores remained above the minimal clinically important difference of 10 throughout. The proportion of patients achieving a GAS T-score ≥ 50 increased from 64.5% in Cycle 1 to 75.8% in Cycle 4. Use of injection guidance techniques significantly increased the odds of achieving treatment goals (OR 1.92; 95% CI 1.45–2.55) and being a “best” responder (OR 2.44; 95% CI 1.47–4.06). Higher BoNT-A doses were also associated with better outcomes. Conclusions: Repeated BoNT-A treatment supports sustained goal attainment in upper limb spasticity. Success rates improve with each cycle, particularly when guided injection techniques are used.

Objective:To evaluate the effect of repeat abobotulinumtoxinA treatment on quality of life (QOL) in patients with leg spasticity. Design:Secondary analysis of the prospective, longitudinal (16mo), observational AboLiSh study. Setting:Specialist neurorehabilitation centers across 9 countries. Participants:Ambulatory adults (66.4% men, mean age 53.9y) with unilateral lower limb spasticity able to take ≥5 steps with or without assistance. Interventions:Patients were treated with abobotulinumtoxinA (up to 6 cycles) per local guidelines to achieve individualized treatment goals. Main Outcome Measures:QOL was assessed at the start of each cycle using the symptom-specific Leg Activity measure (LegA; Parts A: passive function, B: active function, C: QOL impact) and the generic EQ-5D-5L scale. Results:At the population level, QOL improved on both scales across the first 4 treatment cycles. LegA Part C scores decreased and EQ-5D-5L index values increased with repeat treatment. LegA Part C scores showed moderate-to-strong inverse correlations with EQ-5D-5L index values at each cycle (Pearson's R: Cycle 1: -0.66; Cycle 2: -0.57; Cycle 3: -0.60; Cycle 4: -0.59; all P<.0001). LegA Part A scores were moderately-to-strongly correlated with EQ-5D-5L self-care domain scores across cycles 1-3 (Pearson's R: Cycle 1: 0.60; Cycle 2: 0.58; Cycle 3: 0.50; Cycle 4: 0.34; all P<.0001). LegA Part B scores were moderately-to-strongly correlated with EQ-5D-5L mobility domain scores across all cycles (Pearson's R: Cycle 1, 0.58; Cycle 2, 0.57; Cycle 3, 0.57; Cycle 4, 0.59; all P<.0001). Conclusions:Repeat lower limb treatment with abobotulinumtoxinA improved QOL as assessed by both symptom-specific and generic instruments. The significant correlations between LegA Part C and EQ-5D-5L support validity of the LegA to assess the impact of treatment on QOL in patients with leg spasticity.

Abstract Background and aims Up to 40% of stroke survivors will develop spasticity which may affect mobility and cause pain. We evaluated longitudinal goal attainment with repeated abobotulinumtoxinA (aboBoNT-A) injections for leg spasticity management in routine clinical practice. Methods AboLiSh was a 16-month observational study (NCT04050527) of ambulatory adults (≥18y, able to take ≥5 steps) with unilateral leg spasticity treated with aboBoNT-A per local guidelines to achieve personalised goals. Post-hoc analyses assessed cumulative goal attainment (GAS-leg) across cycles in stroke survivors with ≥1 injection and ≥1 GAS-leg assessment (n=328). Results At Cycle 1, the most popular primary goals were related to locomotion (39.6%) followed by pain/discomfort (18.6%). At Cycle 1, the median aboBoNT-A dose for the leg was 600U [range 100-1500U]. Muscle selection was consistent with foot equinus and/or varus; the most commonly injected muscles were the gastrocnemius (medial head 84%; lateral head 74%), soleus (67%), tibialis posterior (52%), flexor digitorum longus (41%), and flexor hallucis longus (22%). 64% of participants also required injections for arm spasticity; in these cases the median total body dose increased to 1362.5U. Goals were generally achieved as expected over repeated cycles. The mean [95%CI] cumulated GAS-leg T score at 16 months was 48.2 [47.5, 49.0] (median: 50). Change in cumulated GAS T scores were clinically relevant; the mean change in GAS-leg score was 9.9 [9.1, 10.7] (median: 10). Conclusions Results from this prospective, longitudinal real-world study demonstrate the sustained functional benefit of repeated cycles of aboBoNT-A for leg spasticity, as assessed by person-centered goal attainment. Conflict of interest Richard D. Zorowitz, Stephen Ashford, Jorge Jacinto and Alberto Esquenazi are part of the AboLiSh study which is sponsored by Ipsen. Mathieu Beneteau, Pascal Maisonobe, and Christian Hannes are employed by Ipsen.

Objective: Describe abobotulinumtoxinA (aboBoNT-A) dosing parameters in the real-world management of lower limb spasticity (LLS). Methods: Prospective, observational study (NCT0​4050527) following ambulatory adults with unilateral LLS treated with aboBoNT-A. Results: The effectiveness population included 384 adults with LLS. Across the study, total lower limb doses were higher in patients who received only lower limb injections (n = 131, median 771U) than those who also received ≥ 1 upper limb injection (n = 253, 567U). Total doses increased over subsequent cycles in both subgroups. Six muscles (gastrocnemius medial and lateral heads, soleus muscle, tibialis posterior, flexor digitorum longus, and flexor hallucis longus) were identified as the main targets for the treatment of LLS; other lower limb muscles were injected in fewer than 15% of patients. The most frequent therapy interventions (mean ± SD of 1.8 ± 1.3h/week with a qualified therapist and 5.3 ± 5.9h/week self-rehabilitation in Cycle 1) were task-specific practice, passive stretch, strength training, and positioning. Conclusions: This study demonstrates how a diversity of muscle patterns are currently treated in routine practice where the primary goal was related to the lower limb and highlights important issues for further debate, such as potential underdosing and the need to balance upper and lower limb priorities when devising a treatment plan.

BackgroundAbobotulinumtoxinA (aboBoNT-A) is approved worldwide in indications related to excessive muscle activity, including focal upper and lower limb spasticity.ObjectiveWe evaluated real-world outcomes associated with on-label use of aboBoNT-A for adult focal spasticity in UK routine clinical practice.MethodsThis was a multicenter, retrospective, 52-week study analyzing data from patients who had received ≥1 injection of aboBoNT-A in line with the Summary of Product Characteristics. Primary endpoints were the average aboBoNT-A dose received per treatment cycle and average interval between cycles.ResultsFor the 108 patients included, the median (Q1, Q3) age was 52.5 (41.0, 69.0) years and the most common underlying neurological condition was stroke (61.1%). The mean (SD) total dose of aboBoNT-A received was 540.8 (268.5) U (cycle 1), 586.1 (279.4) U (cycle 2), 558.0 (258.5) U (cycle 3), and 464.3 (209.6) U (cycle 4). The mean (SD) interval between cycles was 153.8 (56.9) days. Of 82 goals assessed, 71 (86.6%) were achieved. Seven patients (5.8%) in the safety population (N = 121) experienced adverse events, none of which were considered related to aboBoNT-A treatment.ConclusionsThese data further document aboBoNT-A as an effective and well-tolerated treatment for adult focal spasticity, supporting use in clinical practice.

Objective: To assess longitudinal goal attainment with repeat abobotulinumtoxinA (AboBoNT-A) injections for lower limb spasticity (LLS) over 16 months. Design: Prospective, longitudinal, international, multicenter, observational study (NCT04050527). Setting: Specialist neurorehabilitation centers. Participants: Ambulatory adults with unilateral LLS able to take >= 5 steps with/without assistance (effectiveness population, N=384). Interventions: Participants received >= 1 AboBoNT-A treatment cycle administered in accordance with local prescribing guidelines to achieve individualized treatment goals. Main Outcome Measures: The primary endpoint was goal attainment as assessed using the cumulated Goal Attainment Scaling-Leg (GAS-leg) T score, across all treatment cycles for each patient. Results: Overall, participants underwent a median of 5 lower limb injection cycles (median dose 600U, range 100-1475U) with a mean +/- SD injection interval of 18.3 +/- 6.1 weeks. Participants generally achieved their goals as expected over repeated cycles; the mean (95% CI) GAS-leg T score at cycle 1 baseline was 38.0 (37.7, 38.3) and the mean cumulated GAS-leg T score at 16 months was 48.2 (47.4, 48.9) (mean change from a baseline of 9.9 [9.1, 10.7]). Participants injected with a guidance technique at baseline were more likely to attain their cycle 1 primary treatment goals (odds ratio: 1.9 [95% CI 1.1, 3.1], P=.02). Overall, 56 (13.5%) participants reported >= 1 adverse event, of which 6 participants (1.4%) had a treatment-related adverse event. Conclusions: Findings from this large, international study provide evidence for the benefit of repeated cycles of AboBoNT-A for LLS. Multivariate analyses indicated that goal attainment during the first cycle was better with those injected using injection guidance than those injected without guidance. Archives of Physical Medicine and Rehabilitation 2025;106:894-901 (c) 2024 by the American Congress of Rehabilitation Medicine. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

We conducted a multicenter and retrospective study to describe the use of botulinum toxin type A (BoNT-A) to treat post-stroke spasticity (PSS). Data were extracted from free-text in electronic health records (EHRs) in five Spanish hospitals. We included adults diagnosed with PSS between January 2015 and December 2019, stratified into BoNT-A-treated and untreated groups. We used EHRead® technology, which incorporates natural language processing and machine learning, as well as SNOMED CT terminology. We analyzed demographic data, stroke characteristics, BoNT-A use patterns, and other treatments. We reviewed the EHRs of 1,233,929 patients and identified 2190 people with PSS with a median age of 69 years; in total, 52.1% were men, 70.7% had cardiovascular risk factors, and 63.2% had suffered an ischemic stroke. Among the PSS patients, 25.5% received BoNT-A at least once. The median time from stroke to spasticity onset was 205 days, and the time from stroke to the first BoNT-A injection was 364 days. The primary goal of BoNT-A treatment was pain control. Among the study cohort, rehabilitation was the most common non-pharmacological treatment (95.5%). Only 3.3% had recorded monitoring scales. In conclusion, a quarter of patients with PSS received BoNT-A mainly for pain relief, typically one year after the stroke. Early treatment, disease monitoring, and better data documentation in EHRs are crucial to improve PSS patients’ care.