Efficacy and safety of early use of abobotulinumtoxinA in adults with post-stroke spasticity: Results from the ONTIME and ABCDE-S studies

Abstract

Initial muscle tone increase may be apparent within 6 weeks, and even days, post-stroke. Botulinum toxin-A (BoNT-A), an effective and well-tolerated treatment for upper limb spasticity (ULS), improves muscle tone and function, however most studies were conducted > 6 months post-stroke. The ONTIME and ABCDE-S studies assessed efficacy and safety of early use (2–12 weeks post-stroke) of abobotulinumtoxinA (aboBoNT-A) in ULS. ABCDE-S ( NCT00234546 ; 2008): 24-week, randomised (1:1 aboBoNT-A [ n = 80]: placebo [ n = 83]), study assessing muscle tone changes in patients treated within 2–12 weeks of first stroke, with a Modified Ashworth Scale (MAS) score ≥ 1+. ONTIME ( NCT02321436 ; 2016): 28-week, randomised study (2:1 aboBoNT-A [ n = 28]: placebo [ n = 14]), assessing time to appearance or reappearance of reinjection criteria in patients with MAS score ≥ 2 treated 2–12 weeks post-stroke. All observed or volunteered adverse events (AEs) were recorded. MAS score improvements at Week 4 were greater in aboBoNT-A-treated patients than placebo in both studies (ABCDE-S −1.5 vs. −0.5; ONTIME −1.25 vs. −0.25). At 12-weeks post-injection, fewer aboBoNT-A-treated patients versus placebo had MAS scores ≥ 2 in ONTIME (29.6 vs. 69.2%) and ABCDE (21.3 vs. 60.2%) ( Table 1 ). In ONTIME, 11 (39.3%) aboBoNT-A-treated patients did not require reinjection for ≥ 28 weeks versus 2 (14.3%) for placebo. AboBoNT-A was well-tolerated; most AEs were mild–moderate in intensity, with no clinically significant differences in AEs between groups ( Table 2 ). Six patients had treatment-related AEs: two in placebo groups (dysuria and complex regional pain syndrome), and four in aboBoNT-A groups (fatigue [ n = 2], pyrexia, muscular weakness). No serious AEs or deaths were considered treatment-related. Early treatment with aboBoNT-A (2–12 weeks) was well-tolerated and had a longer time to reinjection versus placebo.