评估胍法辛治疗迟发性运动障碍的疗效：KINECT 3 研究的附加结果。

Characterizing Treatment Effects of Valbenazine for Tardive Dyskinesia: Additional Results From the KINECT 3 Study.

机构信息

75-59 263rd St, Glen Oaks, NY 11004.

Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, New York, USA.

出版信息

J Clin Psychiatry. 2018 Dec 18;80(1):18m12278. doi: 10.4088/JCP.18m12278.

DOI:10.4088/JCP.18m12278

PMID:30695293

Abstract

BACKGROUND

In the KINECT 3 (NCT02274558; October 2014 to September 2015) study, valbenazine efficacy in tardive dyskinesia (TD) was demonstrated based on mean changes from baseline in the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1-7). Data from this study were analyzed further to provide a more clinically meaningful interpretation of the primary AIMS results.

METHODS

The study included adults who had a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or any mood disorder and also met DSM-IV criteria for neuroleptic-induced TD. Study participants received 6 weeks of double-blind treatment with valbenazine (40 or 80 mg/d) or placebo. Post hoc AIMS analyses, based on available data, included Cohen d effect sizes, response analyses with odds ratios (ORs) and numbers needed to treat (NNTs), and shift analyses.

RESULTS

At week 6 (N = 202), medium-to-high effect sizes were found for mean improvements in AIMS total score (40 mg/d, d = 0.52; 80 mg/d, d = 0.89). For AIMS total score responses of ≥ 10% to ≥ 70% improvement from baseline, statistical significance was found for valbenazine 80 mg/d versus placebo (P ≤ .01), with ORs (range, 3.0-10.3) and NNTs (range, 3-9) indicating clinical relevance. For response per AIMS item (score ≤ 1 at week 6), significant differences between valbenazine (both doses or 80 mg/d) and placebo were found in the lips, jaw, tongue, and upper extremities. In participants who had an AIMS item score ≥ 1 at baseline, the percentage with a ≥ 1-point improvement at week 6 (shift) was significantly higher with valbenazine (40 and/or 80 mg/d) versus placebo in all 7 body regions.

CONCLUSIONS

Consistent with primary published results for KINECT 3, these supplemental analyses indicate that participants treated with valbenazine (40 or 80 mg/d) had statistically significant and clinically relevant improvements in TD severity both overall and in specific body regions.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT02274558.

摘要

背景

在 KINECT 3 研究（NCT02274558；2014 年 10 月至 2015 年 9 月）中，基于基线时异常不自主运动量表（AIMS）总分（项目 1-7 的总和）的变化，证明了 valbenazine 在迟发性运动障碍（TD）中的疗效。对这项研究的数据进行了进一步分析，以更具临床意义的方式解释主要 AIMS 结果。

方法

该研究纳入了符合 DSM-IV 精神分裂症、分裂情感障碍或任何心境障碍诊断标准，且符合 DSM-IV 神经阻滞剂所致 TD 标准的成年人。研究参与者接受了 6 周的 valbenazine（40 或 80mg/d）或安慰剂的双盲治疗。根据可用数据进行的事后 AIMS 分析包括 Cohen d 效应大小、比值比（OR）和需要治疗的人数（NNT）的反应分析，以及移位分析。

结果

在第 6 周（N=202），发现 AIMS 总分的平均改善具有中到高的效应大小（40mg/d，d=0.52；80mg/d，d=0.89）。对于 AIMS 总分的反应，从基线改善≥10%至≥70%，valbenazine 80mg/d 与安慰剂相比具有统计学意义（P≤.01），OR（范围，3.0-10.3）和 NNT（范围，3-9）表明具有临床相关性。对于每个 AIMS 项目的反应（第 6 周得分≤1），在 valbenazine（两个剂量或 80mg/d）和安慰剂之间发现嘴唇、下巴、舌头和上肢之间存在显著差异。在基线 AIMS 项目得分≥1 的参与者中，与安慰剂相比，valbenazine（40 或 80mg/d）在所有 7 个身体部位的第 6 周（移位）改善≥1 分的百分比显著更高。