Longitudinal goal attainment with integrated upper limb spasticity management including repeat injections of botulinum toxin A: Findings from the prospective, observational Upper Limb International Spasticity (ULIS-III) cohort study

Abstract

Objective To assess the longitudinal effects of integrated spasticity management incorporating repeated cycles of botulinum toxin A type A (BoNT-A) over 2 years. Methods The Upper Limb International Spasticity study was a prospective, observational, cohort study following adult patients over 2 years of integrated upper-limb spasticity management including repeat botulinum toxin (BoNT-A) treatment (any commercially-available product). Results A total of 1,004 participants from 14 countries were enrolled, of which 953 underwent ≥ 1 BoNT-A injection cycle (median 4 cycles) and had ≥ 1 goal attainment scaling assessment. Most participants (55.9–64.6% across cycles 1–6) saw a therapist after BoNT-A treatment; the most frequent therapy intervention was passive stretch (70.1–79.8% across cycles 1–6). Patients achieved their goals as expected over repeated cycles; mean cumulated goal attainment scaling T-score at 2 years was 49.5 (49.1, 49.9). Mean goal attainment scaling change scores of ≥ 10 were maintained across up to 7 cycles. Higher rates of goal achievement were seen for primary goals related to passive vs active function (86.6% vs 71.4% achievement). Standardized measures of spasticity, pain, involuntary movements, active and passive function improved significantly over the study. CONCLUSION This large, international study provides evidence for benefit of repeated cycles of BoNT-A, over 2 years captured through person-centred goal attainment and standardized measures. LAY ABSTRACT This paper presents the primary efficacy results from the Upper Limb International Spasticity (ULIS-III) study, a large international longitudinal study that explored real-life clinical practice in the integrated management of upper-limb spasticity, using botulinum toxin-A (BoNT-A) in conjunction with physical therapies. The study provides evidence for the sustained functional benefit of repeated cycles of BoNT-A. In particular, those patients who continued to receive repeated injections for up to 7 cycles in 2 years showed relevant goal attainment. Standard outcome measures generally supported the rates of goal achievement; ratings of pain, involuntary movements, active and passive function all improved significantly over each treatment cycle. The successful results from ULIS-III highlight the importance of accurate and clear goal-setting during BoNT-A treatment to help target clinical intervention and the use of focused outcome measurement.

Pain Reduction in Adults with Limb Spasticity Following Treatment with IncobotulinumtoxinA: A Pooled Analysis

“…At the time when the studies included in this analysis were conducted, there was a lack of instruments specifically for measuring spasticity-associated pain. Most studies used non-specific pain scales, including numeric rating scales [20,23,25,32,39,40] or visual analogue scales (the most validated outcome measure in pain) [24,26,28,29,41] with score ranges of 0-10; a few used the DAS [21,24,30,31]. Since then, an instrument specifically for measuring spasticity-associated pain has been developed (the Questionnaire on Pain caused by Spasticity [QPS]; [42]), and this was used in later pediatric studies.…”

“…Another consideration is that the priority goal of such treatment may change with time and continuing treatment. In real-life clinical practice, patients with upper limb spasticity have multiple goals for treatment, including improvements in function, pain, mobility, sleep and quality of life [39][40][41], but successful pain management could positively contribute to the achievement of these goals.…”

Comparative efficacy, safety, and cost-effectiveness of abobotulinumtoxinA and onabotulinumtoxinA in children with upper limb spasticity: a systematic literature review, indirect treatment comparison, and economic evaluation

“…For simplicity, response rates were based on the 16 week observations analysed in the NMA, and assumed to be constant in case of further injections. This is likely conservative, as studies of BoNT-A injections for adult upper limb spasticity show increased response rates after repeated A c c e p t e d M a n u s c r i p t injections; 76,77 however, long-term follow-up across multiple injections have not been published for pediatric patients. The result of economic dominance of abo-BoNT-A relative to ona-BoNT-A remained consistent across the PSA and DSA, suggesting that the presence of uncertainty was not likely to influence the overall interpretation of the economic comparison.…”

AbobotulinumtoxinA Versus OnabotulinumtoxinA in Adults with Upper Limb Spasticity: A Randomized, Double-Blind, Crossover Study Protocol

“…The primary hypothesis is that there is comparable safety between products and, as such, the study is powered for a non-inferiority design. The secondary hypothesis is that while there is a similar efficacy profile between both products at peak effect (week 4), aboBoNT-A has a longer duration of effect than onaBoNT-A (based on prior observational data [ 14 ]). This hypothesis will be associated with a conservative hierarchical secondary efficacy endpoint analysis based on superiority tests, with Bonferroni adjustments for multiplicity.…”

“…However, while both products alleviate clinical symptoms of spasticity compared to placebo, their safety and efficacy have never been compared in a blinded prospective study. Recent observational studies suggest differences in the intervals needed between injections (with patients on aboBoNT-A having longer intervals between injections than onaBoNT-A) [ 14 ], but such observations require prospective confirmation. Such information on the potential differences of each product is of great importance to inform treatment decisions.…”