Objective: To reanalyze the Tardive Dyskinesia Impact Scale (TDIS) and assess its potential utility in future TD studies.

Background: TD is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Clinician-rated outcomes, such as the Abnormal Involuntary Movement Scale (AIMS), are used to assess the severity of TD symptoms. However, there is a need for a TD-specific patient-reported outcome (PRO) that assesses the social and emotional impact of these symptoms, such as the TDIS. This PRO was first used as an exploratory measure in the 6-week, double-blind, placebo (PBO)-controlled period of KINECT 3 (phase 3 trial of valbenazine [VBZ]). KINECT 3 was powered to detect treatment differences for AIMS, but not TDIS. However, numerically greater mean improvements from baseline to Week 6 in TDIS total score were found with VBZ (40 and 80 mg, once-daily) versus PBO, raising the question of whether a treatment effect could be observed if TDIS was refined.

Method: KINECT 3 data were re-analyzed in participants classified by psychiatric disorder (schizophrenic/schizoaffective disorder [SZD], mood disorder). Post hoc factor analyses indicated that 8 of the 11 TDIS items loaded onto 4 factors: speech, dexterity, mobility, and emotional. Three items (TD pain, difficulty swallowing, unwanted attention) were not retained, yielding an 8-item TDIS-BRIEF (total score range, 0 to 32 [no to maximum impact]). Regression methods were used to evaluate treatment effects when using TDIS-BRIEF.

Results: Baseline characteristics in the intent-to-treat population (N=225) were as follows: age range, 26-84 years; 53.8% male; 56.9% white/Caucasian; 65.8% schizophrenia/SZD; 34.2% mood disorder. Regressions suggested a strong PBO effect, which may have limited results in mood disorder participants (smaller subgroup) and for the lower VBZ dose (40 mg). However, a notable and statistically significant difference between VBZ 80 mg and PBO was found in the larger subgroup of participants with schizophrenia/SZD (P<0.05).

Conclusion: A novel TD-specific PRO shows potential for further use in clinical trials, as demonstrated in a Phase 3 dataset. Even with a strong PBO response, a significant improvement in the TDIS-BRIEF was found with VBZ 80 mg in the larger subgroup (schizophrenia/SZD).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/reanalysis-of-a-patient-reported-outcome-tardive-dyskinesia-impact-scale-shows-positive-results/