The Effects of Waning of Botulinum Toxin in the Treatment of Cervical Dystonia

Cervical dystonia (CD) is a disabling and often painful condition clinically characterized by abnormal neck and head postures and movements often associated with tremor and chronic pain. Botulinum toxin type A (BoNT-A) is an effective and safe first-line therapy for CD. However, in a recent patient perspective survey, symptom re-emergence between injections (a mean 10.5 weeks) was reported in 88% of patients with a waning time of ≤8 weeks in one-third of patients. Waning treatment effects prior to re-injection reduces quality of life as 47% of patients are somewhat satisfied, and 39% were not satisfied with their therapy as symptoms may follow a "yo-yo" pattern . 45% of patients would prefer a ≤10-week treatment cycle due to the short therapeutic response. However, practicality of injecting patients more frequently and concerns about potential immunologically mediated resistance to BoNT-A has resulted in a standard of treating at intervals of at least 12 weeks. Thus, a significant unmet need is a long-lasting therapy that delays symptom re-emergence and may improve patient satisfaction and outcomes.

Nine published clinical studies have studied the direct comparison between Botox and Dysport in CD patients and authors concluded that a simple dose-conversion factor is not applicable as the ratio for Botox to Dysport was extremely variable, ranging from 1.2 to 13.3. Yun et al demonstrated that conversion to Dysport using a Botox:Dysport ratio of 1:2.5 was not inferior to Botox. A double blind, crossover study lasting 3 injection cycles studied 2 ratios (1:3 and 1:4) and found at both conversion ratios, Dysport was superior to Botox in terms of symptom reduction and duration of effect, although higher frequency of adverse effects such as dysphagia was reported. More recently, a double-blind, randomized crossover study evaluated 2 conversion ratios (1:3 and 1:1.7) that did not show any differences in efficacy in the short term, but the effect of Botox was reduced after 3 months. At week 12, a statistically significant difference in efficacy between abobotulinumtoxinA and onabotulinumtoxinA (1:3) was observed, suggesting a shorter duration of effect for the latter when this ratio (at low dose) was used. Thus, in this research study, the objective is to determine if conversion ratio of 1:2.5 (Botox:Dysport) from the patient's optimized, stable treatment (either Botox or Xeomin) can increase duration of BoNT-A efficacy.

A pilot study published by our research group reported a significant increase in waning time and efficacy following the conversion to aboBoNT-A in 27 CD patients who had a waning time of ≤8-weeks on their original BoNT-A formulation (either onaBoNT-A/incoBoNT-A). The results of the pilot study were limited by the lack of participant blinding and absence of a control group. Thus, a randomized, controlled, single-blind study will be conducted to determine whether the conversion to aboBoNT-A affects waning time, clinical outcomes and treatment satisfaction in patients experiencing early waning with ona/incoBoNT-A.

• • Modified Tsui Scale [Time frame: At the end of each cycle for 3 cycles. Each cycle is 12 weeks in duration as the reinjection is done every 12 weeks.]
• • 5-point Likert participant reported treatment satisfaction tool [Time frame: At the end of each cycle for 3 cycles. Each cycle is 12 weeks in duration as the reinjection is done every 12 weeks.]
• • Onset of treatment relief using the symptom tracker [Time frame: At the end of each cycle for 3 cycles. Each cycle is 12 weeks in duration as the reinjection is done every 12 weeks.]
• • Safety of the use of botulinum toxin injection for cervical dystonia [Time frame: At the end of each cycle for 3 cycles. Each cycle is 12 weeks in duration as the reinjection is done every 12 weeks.]