Objective: To evaluate the safety and efficacy of abobotulinumtoxinA in comparison to onabotulinumtoxinA when used at optimized doses in approved muscles common to both products’ US FDA labels.
Background: The safety and efficacy of both abobotulinumtoxinA and onabotulinumtoxinA for upper-limb spasticity has previously been established (Level 1), but head-to-head comparisons are lacking.
Method: DIRECTION is a phase IV, international, interventional, randomized, double-blind, crossover study comparing abobotulinumtoxinA with onabotulinumtoxinA in the management of ULS. An estimated 650 participants (18-75y) with ULS will be screened to achieve enrolment of 564 randomized patients. Participants will be randomized (1:1) to two treatment sequences – either one cycle of abobotulinumtoxinA (900U) followed by one cycle of onabotulinumtoxinA (360U) or vice versa. To maintain study blinding, a fixed volume (3.6mL) will be injected into the target upper-limb muscles (4 palmar flexors and biceps brachii) using guidance techniques. Participants will begin the second treatment cycle at Week 12 if retreatment criteria are fulfilled. If not, participants will be reassessed every 4 weeks (at Weeks 16, 20 and 24) until they require retreatment. The primary hypothesis is that the safety profiles of both products are comparable (non-inferiority will be tested based on TEAE rates from injection to Week 12). A secondary hypothesis is that abobotulinumtoxinA has longer duration of effect than onabotulinumtoxinA; this hypothesis will be based on superiority tests associated with secondary efficacy endpoints analyses (including injection cycle duration, Modified Ashworth Scale, Disability Assessment Scale and Physician Global Assessment).
Results: The DIRECTION study will complete in 2023.
Conclusion: Using clinically relevant dosing, the DIRECTION study will be the first to prospectively compare abobotulinumtoxinA with onabotulinumtoxinA to allow informed therapeutic decisions for care optimization, including use of optimized dosing- according to the approved prescribing information.
To cite this abstract in AMA style:
A. Esquenazi, Z. Ayyoub, M. Verduzco-Gutierrez, P. Maisonobe, J. Otto, A. Patel. A phase IV, randomized, double-blind cross-over study comparing the clinical safety, efficacy and duration of abobotulinumtoxinA with onabotulinumtoxinA in adults with upper-limb spasticity: The DIRECTION study [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/a-phase-iv-randomized-double-blind-cross-over-study-comparing-the-clinical-safety-efficacy-and-duration-of-abobotulinumtoxina-with-onabotulinumtoxina-in-adults-with-upper-limb-spasticity-the-direc/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-phase-iv-randomized-double-blind-cross-over-study-comparing-the-clinical-safety-efficacy-and-duration-of-abobotulinumtoxina-with-onabotulinumtoxina-in-adults-with-upper-limb-spasticity-the-direc/