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

Abstract

Introduction The safety and efficacy of both abobotulinumtoxinA and onabotulinumtoxinA for upper limb spasticity are well established, but head-to-head comparisons are lacking. Methods DIRECTION is an international, randomized, double-blind, crossover study comparing the safety and efficacy of abobotulinumtoxinA with onabotulinumtoxinA in the management of upper limb spasticity at doses at or near maximum recommended in product labelling. Participants (18–75 years) will be randomized (1:1) to either one cycle of abobotulinumtoxinA (900U) followed by onabotulinumtoxinA (360U) or vice versa. To maintain blinding, a fixed volume (3.6 ml) will be injected into the target upper limb muscles (four wrist and finger flexors and biceps brachii). The second treatment cycle will begin at Week 12 if retreatment criteria are fulfilled, and if not, they will be reassessed every 4 weeks until they meet retreatment parameters. Planned Outcomes The primary hypothesis is that there is comparable safety between products; non-inferiority will be tested based on treatment-emergent adverse event (TEAE) rates from injection to Week 12. A secondary hypothesis is that abobotulinumtoxinA has longer duration of effect than onabotulinumtoxinA. This hypothesis will be tested with secondary efficacy endpoints, including injection cycle duration, Modified Ashworth Scale, Disability Assessment Scale and Physician Global Assessment. Trial Registration EudraCT ( http://eudract.ema.europa.eu ): 2021-000161-32 and Clinicaltrials.gov ( http://clinicaltrials.gov ): NCT04936542. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01896-3.

Exploring high-density corticomuscular networks after stroke to enable a hybrid Brain-Computer Interface for hand motor rehabilitation

“…Among those, the highest values are observed in the ipsilateral BIC muscle. The bicep is crucial for post stroke upper limb flexion spasticity [ 40 ] as testified by clinical studies [ 41 , 42 ]. Despite the low or absent clinical spasticity in our patients (as assessed by MAS) we argue that this finding may represent a subclinical substrate for elbow flexion spasticity; future studies involving stroke patients showing higher level of spasticity are needed to definitely corroborate this argumentation.…”

Update on Non-Interchangeability of Botulinum Neurotoxin Products

“…Given these differences, comparing the products in spasticity using the same injection paradigm may favor one product over another. For instance, a recent study uses the same injection sites for both onabotA and abobotA in upper limb spasticity, limits injection sites to 5 pre-identified muscles for both, and avoids the finger flexors [ 190 ].…”

“…Given that each of these guides uses different photos to define their ratings, they are not identical, making it difficult to draw conclusions about BoNT comparability across studies. In the therapeutic literature, different scales have been used to evaluate cervical dystonia (e.g., Cervical Dystonia Severity Scale [ 183 ], Toronto Western Spasmodic Torticollis Scale [ 187 ]) and spasticity (e.g., Ashworth scale [ 196 ], modified Ashworth scale [ 190 ], modified Tardieu scale [ 197 ], individual goal attainment scales [ 198 ]).…”