New phase 4 head-to-head data suggest Dysport may provide longer-lasting symptom control than Botox in adults with upper limb spasticity while maintaining comparable safety.
New late-breaking findings from the phase 4 DIRECTION trial (NCT04936542) showed that treatment with Dysport (abobotulinumtoxinA; Ipsen) demonstrated a noninferior safety profile to Botox (onabotulinumtoxinA; AbbVie) in adults with upper limb spasticity (ULS), while also providing a longer duration of response. The data, presented at the 2026 International Society of Physical and Rehabilitation Medicine (ISPRM) World Congress in Vancouver, marked the first prospective, randomized, double-blind head-to-head comparison between the 2 botulinum toxin type A therapies in spasticity.1
The DIRECTION study met both its primary safety endpoint and key secondary efficacy endpoint. Treatment-emergent adverse events occurred in 20.3% of patients treated with Dysport compared with 23.0% of those treated with Botox, yielding an adjusted treatment difference of –2.7% (80% CI, –6.2 to 0.9).
In addition, patients receiving Dysport achieved a longer duration of therapeutic response than those treated with Botox, with treatment effects lasting 14.2 weeks versus 13.8 weeks, respectively (adjusted difference favoring Dysport; 80% CI, 0.2-5.9). Investigators noted that evidence of longer duration was consistent across most demographic and clinical subgroups.
“Today, for the first time, we have comparative evidence that distinguishes the performance of two widely used botulinum toxin treatments in patients with spasticity,” Alberto Esquenazi, MD, principal investigator of DIRECTION and Chief Clinical Officer of Jefferson Moss-Magee Rehabilitation, said in a statement.1 “These findings are based on a rigorously controlled study design and contribute meaningful data for clinicians, strengthening the evidence available for the use of botulinum toxin therapies in people with spasticity.”
Upper limb spasticity is a disabling complication commonly seen after stroke, traumatic brain injury, multiple sclerosis, cerebral palsy, and other neurologic conditions. Characterized by increased muscle tone, involuntary contractions, stiffness, and impaired voluntary movement, ULS can substantially affect hygiene, dressing, limb positioning, pain, and overall quality of life. Botulinum toxin injections are widely considered first-line focal therapy because they reduce excessive muscle contraction by blocking acetylcholine release at the neuromuscular junction.
DIRECTION enrolled 464 adults with ULS across 72 sites in the United States, Canada, and France. Most participants developed spasticity following stroke, and the average patient age was 57 years. The randomized, double-blind crossover study compared a total dose of 900 U Dysport with 360 U Botox using standardized injection paradigms and instrument-guided administration techniques to minimize variability between treatments. Eligibility criteria required participants to have stable upper limb spasticity for at least 3 months, Modified Ashworth Scale scores of at least 2 in key muscle groups, and clinically meaningful disability based on Disability Assessment Scale scoring.
The study specifically evaluated injections into the flexor carpi radialis, flexor carpi ulnaris, flexor digitorum profundus, flexor digitorum superficialis, and biceps brachii muscles, reflecting commonly targeted muscle groups in clinical practice. Participants requiring treatment in additional limbs or muscle groups were excluded to preserve consistency across treatment comparisons.
Botulinum toxin therapies have become central to the management of spasticity over the past 2 decades. Botox, originally approved by the FDA in 1989 for strabismus and blepharospasm, later gained approvals across several neurologic indications, including adult upper limb spasticity in 2010.2,3 Dysport, first approved in Europe in the early 1990s and later in the United States in 2009 for cervical dystonia and cosmetic indications, subsequently received FDA approval for adult upper limb spasticity in 2015.4,5 Both therapies are now widely used across rehabilitation medicine and neurology for spasticity management.
Despite their widespread use, direct comparative evidence between different botulinum toxin products has historically been limited. DIRECTION therefore addresses a longstanding evidence gap by prospectively comparing 2 of the most commonly used formulations under tightly controlled study conditions.1
“Ipsen is committed to generating robust clinical evidence that supports scientific understanding and real-world practice. In spasticity, the durability of treatment response plays a critical role in patients’ function, mobility and quality of life,” Sandra Silvestri, PhD, MD, chief medical officer at Ipsen, said in a statement.1 “The DIRECTION data provides further support that Dysport can delay breakthrough symptoms with a well-established safety profile.”
The durability findings may hold particular clinical relevance because prior research has suggested that more than 80% of patients with spasticity experience breakthrough symptoms between injection cycles, while over 70% report a desire for longer-lasting treatment effects.
