Chorea associated with Huntington’s Disease
The efficacy of Austedo (deutetrabenazine) in the treatment of chorea associated with Huntington's disease was established in a trial that compared Austedo (deutetrabenazine) with placebo (a substance with no therapeutic effect).
The study involved 90 patients with manifest chorea associated with Huntington’s disease but with maintained walking ability1,5.
The study lasted 13 weeks – 12 weeks of treatment and 1 final week of treatment interruption (washout). The 12 weeks of treatment consisted of 8 weeks of gradual dosage increase (titration) and 4 weeks of maintenance1,5.
The initial dose for patients on Austedo (deutetrabenazine) was 6 mg per day and it was incremented at weekly intervals with increments of 6 mg until satisfactory treatment of chorea was achieved, intolerable side effects occurred, or until a maximal dose of 48 mg per day was reached1,5.
The two patient groups (placebo and deutetrabenazine) were compared on the basis of the scores achieved on different scales.
The most important measure was the change in the total maximal chorea score from the beginning of the study (baseline). The total maximal chorea score ranges from 0 to 28, where a lower score indicates less chorea. It is given by the sum of maximal chorea scores for 7 body regions (face, buccal-oral-lingual, trunk, and 4 extremities), each of which is scored on a scale from 0 to 4 (0 = absent; 1 = slight or intermittent; 2 = mild and common or moderate and intermittent; 3 = moderate and common; and 4 = marked and prolonged). Among the other scales used to monitor the patients were the Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), the 36-Item Short Form Health Survey (SF-36) physical functioning subscale score, and Berg Balance Test. The PGIC and CGIC are scales designed to assess the effects of treatment as perceived by patients and clinicians, respectively. The SF36 is a survey on patient health, and the Berg Balance Test is a clinical test of a person's static and dynamic balance abilities5.
Austedo resulted better than placebo in all tests except the Berg Balance Test.
The difference in improvement in total maximal chorea score between the two groups was significantly in favour of Austedo (deutetrabenazine): patients in the deutetrabenazine group had a mean of –4.4 (95 % CI, –5.3 to –3.6) improvement in total maximal chorea score, whereas the placebo group improved by –1.9 (95% CI, –2.8 to –1.1).
Following the treatment interruption (washout), chorea returned to the level it was before the study started1,5.
In the deutetrabenazine group 51% of patients reported treatment success by the PGIC scale versus 20% in the placebo group. Similarly, 42% of patients in the deutetrabenazine group reported treatment success using the CGIC scale vs 13% of patients in the placebo group.
The SF-36 physical functioning subscale improved by 0.7 (95% CI, –2.0 to 3.4) for deutetrabenazine and worsened by –3.6 (95% CI, –6.4 to –0.8) for the placebo group. There was no significant difference in improvement in Berg Balance Test1,5.
The efficacy of Austedo (deutetrabenazine) in the treatment of tardive dyskinesia was established in 2 X 12 week, randomised, double-blind, placebo-controlled, multicentre trials conducted in 335 adult ambulatory patients with tardive dyskinesia caused by the use of antipsychotics (dopamine receptor antagonists)1.
The most important measure in both studies was the change in Abnormal Involuntary Movement Scale (AIMS). The AIMS is a 12 item scale for the assessment of tardive dyskinesia severity. The first 7 items assess the severity of involuntary movements across body regions and these items were used in this study1.
Each of the 7 items was scored on a 0 to 4 scale, with 0 = not present and 4 = severe (abnormal movements occur almost continuously and/or of extreme intensity). The AIMS total score across the 7 considered items could thus range from 0 to 28, with a decrease in score indicating improvement1.
Study 1 involved 222 patients who were divided into 4 groups: 1 group took placebo and the other 3 took Austedo (deutetrabenazine). The treatment included a 4 weeks dose escalation, 8 weeks of maintenance and 1 final week of treatment interruption (washout). Of those that took Austedo, a first group took 12 mg daily for the whole duration of the study, a second group started with 12 mg daily and increased to 24 mg daily, and a third group started with 12 mg daily up to 36 mg daily. Patients receiving the 24 mg and the 36 mg dose had an improvement in the AIMS score of 3.3 and 3.2 units respectively, compared with 1.4 units in the place group1.
Study 2 involved 113 patients. It lasted for 12 weeks, during which Austedo was tested against placebo, adjusting the dose from 12 mg with increases allowed in 6 mg increments at 1 week intervals until satisfactory control of dyskinesia was achieved, intolerable side effects occurred, or a maximal dose of 48 mg per day was reached. The AIMS total score for patients receiving Austedo demonstrated a statistically significant improvement of 3.0 units from baseline to endpoint (week 12), compared with 1.6 units in the placebo group1.