Pivotal Trials Evaluating Dysport’s Impact on Adult Upper Limb Spasticity
In a pivotal randomized, multicenter, double-blind, placebo-controlled study involving 238 adults with post-stroke or post-traumatic brain injury upper limb spasticity (ULS), the efficacy and safety profile of Dysport were meticulously evaluated. The study’s design encompassed both toxin-naive and toxin non-naive participants, with inclusion criteria mandating a Modified Ashworth Scale (MAS) score of ≥2 in the primary target muscle group (PTMG) for toxin-naive individuals or ≥3 at least four months after the last injection for toxin non-naive patients. Additionally, a spasticity angle of ≥10 degrees in the PTMG was required.
Co-Primary Efficacy Endpoints and Baseline Characteristics
The co-primary efficacy endpoints were the mean change in MAS score in the PTMG (elbow, wrist, or finger flexors) and the Physician Global Assessment (PGA) of response to treatment between baseline and Week 4. At baseline, the mean MAS scores were comparable across the treatment groups, with a score of 3.9 (±0.4) for the placebo group, 3.9 (±0.5) for the Dysport 500 Units group, and 3.9 (±0.4) for the Dysport 1000 Units group.
Assessments and Open-Label Treatment Phase
Follow-up assessments were conducted at Weeks 1, 4, and 12, with additional visits permitted at Weeks 16, 20, and 24 as needed for re-treatment. After three months of on-study treatment, patients were given the opportunity to continue open-label treatment with Dysport. In the open-label phase, eligible patients from the double-blind study were offered Dysport for up to four treatment cycles at intervals of at least 12 weeks. A total of 254 patients were enrolled in the study.
Sustained Relief Beyond Minimum Re-Treatment Time
Remarkably, while re-treatment was typically scheduled between 12 and 16 weeks for 83% of patients (Dysport 500 Units and Dysport 1000 Units groups; n=147), some patients experienced a longer duration of response, extending up to 20 weeks. This observation highlights Dysport’s potential to provide sustained relief beyond the minimum re-treatment time for certain individuals.
Re-Treatment Criteria and Timing
In the pivotal trials for adult spasticity, the need for re-treatment was determined by several factors:
- No longer demonstrating a decrease from baseline of ≥1 grade in MAS score in the PTMG
- No improvement in PGA (i.e., a score ≤0)
- No signs of unacceptable safety risk for the next treatment cycle
Investigator discretion, based on efficacy and safety criteria, determined the need for re-treatment in patients demonstrating a decrease from baseline of ≥1 grade in MAS score and/or improvement in PGA (i.e., a score ≥1). Repeat Dysport treatment should be administered no sooner than 12 weeks after the previous injection.
Conclusion
The pivotal trials evaluating Dysport’s efficacy and safety in adult upper and lower limb spasticity, as well as cervical dystonia, have provided valuable insights into its clinical utility. While the results should be interpreted cautiously due to limitations such as potential chance findings at Week 12, the overall data suggest that Dysport treatment may offer significant benefits in managing spasticity and cervical dystonia. Furthermore, the potential for sustained relief beyond the minimum re-treatment time and a favorable safety profile, including low immunogenicity, are encouraging findings. As with any medical intervention, individual patient factors and risks should be carefully considered when determining the appropriateness of Dysport treatment.
