Assessment of Long-term Clinical Response to BoNT in Cervical Dystonia

Study Overview
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Brief Summary
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The goal of this retrospective, international, multi-center chart abstraction is to learn about the long-term impact of product-specific immunogenicity-related factors in different botulinum neurotoxin type A formulations in patients suffering from cervical dystonia. The main question it aims to answer is: Do complex-containing (CC) botulinum toxin formulations impact the long-term clinical outcome in cervical dystonia patients compared to a complex-free (CF) formulation? Researchers will compare differences observed in years 2 and 7 between two toxin groups, i.e., botulinum neurotoxins type A containing complexing proteins (CC) and without complexing proteins (CF).

Detailed Description
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Botulinum neurotoxin type A (BoNT/A) is first-line treatment in patients suffering from cervical dystonia. Effect of BoNT/A is temporary and must be repeated to maintain clinical effect. As for all biologics, repeated treatment bears the risk of activating an immune response due to the immunogenic nature of foreign proteins. Clinical signs of a potential immune response are reduced, or loss of efficacy, decreased duration of effect, and the need of a dose increase to maintain effect. Due to the different degree of purity and protein content, it is reasonable to assume that commercial BoNT/A formulations differ in immunogenic properties. Pivotal clinical trials and monocentric real-world studies demonstrated an increased incidence of neutralizing antibodies (NAbs) and NAb-associated partial or complete secondary non-response. However, the clinical relevance of potential immunogenicity-related mechanisms has not been demonstrated in a larger multicentric cohort in a real-world setting. This chart abstraction is designed to address this gap.

Official Title
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Assessment of Long-term Clinical Response to BoNT in Cervical Dystonia - Real-world Evidence of LongevitY of Botulinum Toxin in Cervical Dystonia

Conditions
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Cervical Dystonia

Intervention / Treatment
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* Biological: CC BoNT/A
* Biological: CF BoNT/A
* Biological: CF to CC BoNT/A
* Biological: CC to CF BoNT/A


Participation Criteria
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Eligibility Criteria
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Clinical diagnosis of cervical dystonia Adults (m/f) 18-64 years of age at start of BoNT/A treatment Patient's written informed consent if required by local and/or national law.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Complex-free BoNT/A formulation<br>Patients exclusively treated with the complex-free (CF) formulation (incobotulinumtoxinA). A maximum of 328 patients will be enrolled in this group. | Biological: CF BoNT/A<br>* Complex-free BotulinumtoxinA (BoNT/A) formulation<br>* Other names: Botulinum toxin type A (150 kiloDalton), free from complexing proteins;|
| Complex-containing BoNT/A formulations<br>Patients exclusively treated with a single complex-containing (CC) formulation (onabotulinumtoxinA or abobotulinumtoxinA). A maximum of 328 patients will be enrolled in this group. | Biological: CC BoNT/A<br>* Complex-containing BotulinumtoxinA (BoNT/A) formulations<br>* Other names: abobotulinumtoxinA;|
| Switcher CF to CC BoNT/A formulations<br>The CF to CC switcher group includes all patients that were switched from a CF to a CC BoNT/A formulation. If more than one switch occurred, the first switch determines the group. Both switcher groups will in sum not exceed 325 patients. | Biological: CF to CC BoNT/A<br>* Switch from complex-free to complex-containing BoNT/A formulations<br>* Other names: abobotulinumtoxinA;|
| Switcher CC to CF BoNT/A formulations<br>The CC to CF switcher group includes all patients that were switched from a CC to a CF BoNT/A formulation. If more than one switch occurred, the first switch determines the group. Both switcher groups will in sum not exceed 325 patients. | Biological: CC to CF BoNT/A<br>* Switch from complex-containing to complex-free BoNT/A formulations<br>* Other names: incobotulinumtoxinA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with a clinically meaningful change in dose-effect at year 7 compared to reference year 2 between complex-free and complex-containing BoNT/A monotherapy | Dose-effect is a change in treatment response following dose adjustment. | Year 2 and year 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical meaningfulness of change in efficacy from baseline (first visit on record) at each visit in years 2, 5, 7, 10 in all treatment groups |  | Baseline (first visit on record), years 2, 5, 7, and 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spasmodic torticollis, focal dystonia