AbobotulinumtoxinA using 2-mL dilution (500 U/2-mL) maintains durable improvement across multiple treatment cycles

Abstract

Background: Cervical dystonia (CD), the most common focal dystonia, is a chronic neurological movement disorder characterized by sustained involuntary contractions of the neck muscles, leading to abnormal postures. AbobotulinumtoxinA (aboBoNT-A) was approved in the US initially as a 500 U per 1-mL dilution and subsequently, as a 500 U/2-mL dilution (or 250 U/mL), thereby providing clinicians with more flexible dosing options to better meet individual patient needs. The objective of this open-label extension study was to evaluate the longer term safety and efficacy of repeat treatments with aboBoNT-A using 2-mL dilutions in adults with cervical dystonia.

Methods: Patients (N = 112) from a 12-week, double-blind lead-in study (NCT01753310) received up to three additional treatments of aboBoNT-A, with re-treatment every 12-16 weeks based on clinical judgment. Safety was assessed through treatment-emergent adverse events (TEAEs). The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total and subscale scores were measured at day 1 of each treatment cycle (C), 4 weeks after each treatment, and 12 weeks after the third treatment. Descriptive statistics were used for all analyses.

Results: In cycles 1, 2, 3, and 4, respectively, 35.7, 25.9, 30.2, and 22.8% of patients reported TEAEs. Dysphagia, muscular weakness, and neck pain were each reported by 10.7% of patients, over the full study duration. Mean TWSTRS total score decreased from 37.7 (SD 13.6 [C1, day 1]) to 30.1 (SD 12.8 [C3, week 12]). In each cycle, TWSTRS total and subscale scores decreased from day 1 to week 4 and increased between weeks 4 and 12, though the week 12 scores remained lower than day 1 scores.

Conclusion: Extended treatment of cervical dystonia with aboBoNT-A (up to 3 additional treatment cycles) using a 2-mL dilution is effective, with a positive risk-benefit profile.

Trial registration: ClinicalTrials.gov Identifier: NCT01753336. Registered 17 Dec 2012.

Keywords: AbobotulinumtoxinA; Cervical dystonia; Efficacy; Open-label extension study; Repeat treatments; Safety.

Conflict of interest statement

Competing interestsKD: Advisor/consultant, and/or speaker: Abbvie, ACADIA, Acorda, Adamas, Allergan, Amneal, Impax, Ipsen, Lundbeck, Neurocrine, Revance, Sunovion, Teva, US WorldMeds; SW: Employment: Ipsen; BR: Employment (former): Ipsen; PM: Employment: Ipsen; LB: Speaker’s bureaus: Allergan, Ipsen, Us WorldMeds; Consultant: US WorldMeds; RT: Speaker and/or Consultant: Ipsen, Neurocrine, Acadia, Amneal, and US WorldMeds.

© The Author(s) 2020.

Figures

Fig. 1

Study Flow Chart. aThis visit should occur on the same day as the last visit of the previous treatment cycle. Re-treatment was expected to occur approximately 12–16 weeks after the last treatment; however, the exact timing of treatment was determined by the investigator based on clinical need. bPatients who withdrew from the study early (ie, before week 12 of cycle 3) underwent all procedures required for the week 36 visit

Fig. 2

Change from baseline in TWSTRS total score. C, cycle; D, day; W, week. *Before first abobotulinumtoxinA administration

Fig. 3

Change from baseline in TWSTRS subscale scores. C, cycle; D, day; W, week. *Before first abobotulinumtoxinA administration