Study Supports Higher Botulinum Toxin Dosing for Cervical Dystonia Treatment

129 patients completed the Phase 3b, double-blind, 12-week study
129 patients completed the Phase 3b, double-blind, 12-week study

VANCOUVER, BC—A higher dosage of abobotulinumtoxinA (DysportIpsen Biopharmaceuticals) was found to significantly improve the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score in patients with cervical dystonia (CD), according to a study presented at the 68th AAN Annual Meeting.

Patients with cervical dystonia experience involuntary cervical muscle contractions that cause sustained and painful head and neck postures. AbobotulinumtoxinA is currently approved by the Food and Drug Administration (FDA) to treat CD, but only in a dilution of 500 Units (U) in 1mL to affected muscles. Some off-label uses of 2mL dilutions have been documented in real-world settings. Mark F. Lew, MD, from the University of Southern California School of Medicine, Los Angeles, CA, and colleagues set out to test the safety and efficacy of a 500U, 2mL dilution of abobotulinumtoxinA vs. placebo in patients with CD through a Phase 3b, double-blind, 12-week study.

One-hundred and twenty-nine patients completed the Week 4 primary endpoint evaluation. Study patients were randomized (2:1) to receive abobotulinumtoxinA (n=84) or placebo (n=45). The randomization was stratified according to whether the patient was onabotulinumtoxinA-naive or was successfully treated with onabotulinumtoxinA for CD. Toxin-naive abobotulinumtoxinA patients received 500U/2mL in ≥2 affected neck muscles, while patients who had previously gotten botulinum treatment (non-naive) received 250–500U/2mL (2.5:1 of previous onabotulinumtoxinA [BotoxAllergan] dose) into affected muscles.

The primary endpoint was change from baseline to Week 4 TWSTRS total score and safety was assessed over the 12-week study period. Secondary efficacy endpoints included change in TWSTRS total score at Week 2, clinical global impression of change (CGIC) at Weeks 2 and 4, and treatment response at Weeks 2 and 4.

Results showed a significantly greater change in TWSTRS score from baseline in the abobotulinumtoxinA treatment group at the Week 4 endpoint vs. placebo (-10.8 vs. -2.5; P<0.001). The difference between treatments was significant as early as Week 2 for the intent-to-treat population, the authors noted (-7.6 vs. -2.6; P=0.001). In regards to CGIC, physicians reported that over half of their patients treated with abobotulinumtoxinA (52.3%) were "very much improved" or "much improved" at Week 4 vs. the 20% of patients treated with placebo. 

The abobotulinumtoxinA treatment group reported more adverse events (41%) compared to the placebo group (22%); dysphagia was reported in 9% of patients.  Other adverse events exclusive to the abobotulinumtoxinA group included muscle weakness, neck pain, and headache.

These findings suggest that a 2mL dilution of abobotulinumtoxinA was safe and effective in patients, supporting dosing flexibility for this patient population. Dr. Lew added that the "treatment-emergent adverse events reported during the study were consistent with the known safety profile of abobotulinumtoxinA for CD patients."

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