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139 Early Response with Valbenazine and Long-Term Symptom Reduction in Patients with Tardive Dyskinesia: Post Hoc Analysis of the KINECT 3 Study
CNS Spectrums ( IF 3.3 ) Pub Date : 2020-04-24 , DOI: 10.1017/s1092852920000553
Stanley N. Caroff , Jean-Pierre Lindenmayer , Stephen R. Marder , Stewart A. Factor , Khodayar Farahmand , Leslie Lundt

:Study Objective:Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Valbenazine is a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of TD in adults. Using data from a long-term study (KINECT 3; NCT02274558), the effects of once-daily valbenazine (40 mg, 80 mg) on TD were assessed using the Abnormal Involuntary Movement Scale (AIMS) in participants who were early responders based on subjective measures, including patient self-report (Patient Global Impression of Change [PGIC]) or clinician judgment (Clinical Impression of Change-Tardive Dyskinesia [CGI-TD]).Methods:Data from KINECT 3 (6-week double-blind, placebo-controlled [DBPC] period; 42-week double-blind extension) were analyzed post hoc. Long-term outcomes included mean change from baseline to Week 48 in AIMS total score (sum of items 1-7) and AIMS response (≥50% total score improvement from baseline) at Week 48. These AIMS outcomes were assessed in participants who achieved early improvement, defined as a PGIC or CGI-TD score of ≤3 (“minimally improved” or better) at Week 2 (first post-baseline visit of the DBPC period). Participants who initially received placebo were not included in the analyses.Results:In participants who received only valbenazine (40 or 80 mg) during KINECT 3 and had available Week 2 assessment, 50% (72/143) had early PGIC improvement (score ≤3) and 43% (61/142) had early CGI-TD improvement (score ≤3). Baseline characteristics were generally similar between participants who achieved early PGIC or CGI-TD improvement and those who did not. Based on available assessments at Week 48, mean AIMS total score change from baseline in participants with early PGIC improvement was similar to those who did not reach the early PGIC improvement threshold (-4.1 [n=35] vs -3.5 [n=41]). Mean AIMS total score change from baseline in participants with early CGI-TD improvement was similar to those who did not achieve early CGI-TD improvement (-4.2 [n=31] vs -3.5 [n=45]). AIMS response at Week 48 was also similar in those who achieved early PGIC and CGI-TD improvement (40% and 42%, respectively) compared to those who did not achieve early PGIC and CGI-TD improvement (39% and 38%, respectively).Conclusions:Results from this long-term valbenazine trial indicate that many participants achieved at least minimal patient- and clinician-reported improvement at Week 2. AIMS outcomes at Week 48 demonstrated long-term reductions in TD severity regardless of early response. More research is needed to understand the association between early improvement and long-term treatment effects, but early non-improvement based on subjective measures may not be predictive of long-term treatment failure.Presented:International Congress of Parkinson’s Disease and Movement Disorders; September 22-26, 2019; Nice, France.Funding Acknowledgements:This study was sponsored by Neurocrine Biosciences, Inc.

中文翻译:

139 缬苯那嗪的早期反应和迟发性运动障碍患者的长期症状减轻:KINECT 3 研究的事后分析

: 研究目的:迟发性运动障碍 (TD) 是一种持续性和可能致残的运动障碍,与长期接触抗精神病药和其他多巴胺受体阻滞剂有关。Valbenazine 是一种高度选择性的囊泡单胺转运蛋白 2 (VMAT2) 抑制剂,被批准用于治疗成人 TD。使用来自一项长期研究(KINECT 3;NCT02274558)的数据,使用异常不自主运动量表(AIMS)评估了每日一次缬苯那嗪(40 毫克、80 毫克)对 TD 的影响,这些量表是基于早期反应者的参与者主观测量,包括患者自我报告(患者总体变化印象 [PGIC])或临床医生判断(变化的临床印象-迟发性运动障碍 [CGI-TD])。方法:来自 KINECT 3 的数据(6 周双盲,安慰剂对照 [DBPC] 期;42 周双盲扩展)进行了事后分析。长期结果包括 AIMS 总分(项目 1-7 的总和)从基线到第 48 周的平均变化和第 48 周的 AIMS 反应(总分比基线提高≥50%)。这些 AIMS 结果在达到早期改善,定义为在第 2 周(DBPC 期的第一次基线后访问)时 PGIC 或 CGI-TD 评分≤3(“最小改善”或更好)。最初接受安慰剂的参与者不包括在分析中。结果:在 KINECT 3 期间仅接受缬苯那嗪(40 或 80 mg)并进行第 2 周评估的参与者中,50% (72/143) 的参与者早期 PGIC 改善(评分≤ 3) 和 43% (61/142) 有早期 CGI-TD 改善(分数 ≤3)。获得早期 PGIC 或 CGI-TD 改善的参与者与未获得改善的参与者之间的基线特征通常相似。根据第 48 周的可用评估,早期 PGIC 改善的参与者的平均 AIMS 总分变化与未达到早期 PGIC 改善阈值的参与者相似(-4.1 [n=35] vs -3.5 [n=41] )。早期 CGI-TD 改善的参与者的平均 AIMS 总分变化与未实现早期 CGI-TD 改善的参与者相似(-4.2 [n=31] vs -3.5 [n=45])。与未实现早期 PGIC 和 CGI​​-TD 改善的患者(分别为 39% 和 38%)相比,获得早期 PGIC 和 CGI​​-TD 改善的患者(分别为 40% 和 42%)在第 48 周的 AIMS 反应也相似).结论:这项长期缬苯那嗪试验的结果表明,许多参与者在第 2 周至少实现了患者和临床医生报告的最小改善。第 48 周的 AIMS 结果表明,无论早期反应如何,TD 严重程度都长期降低。需要更多的研究来了解早期改善与长期治疗效果之间的关联,但基于主观测量的早期未改善可能无法预测长期治疗失败。2019年9月22-26日;法国尼斯。资助致谢:本研究由 Neurocrine Biosciences, Inc. 赞助。第 48 周的 AIMS 结果表明,无论早期反应如何,TD 严重程度都会长期降低。需要更多的研究来了解早期改善与长期治疗效果之间的关联,但基于主观测量的早期未改善可能无法预测长期治疗失败。2019年9月22-26日;法国尼斯。资助致谢:本研究由 Neurocrine Biosciences, Inc. 赞助。第 48 周的 AIMS 结果表明,无论早期反应如何,TD 严重程度都会长期降低。需要更多的研究来了解早期改善与长期治疗效果之间的关联,但基于主观测量的早期未改善可能无法预测长期治疗失败。2019年9月22-26日;法国尼斯。资助致谢:本研究由 Neurocrine Biosciences, Inc. 赞助。2019年9月22-26日;法国尼斯。资助致谢:本研究由 Neurocrine Biosciences, Inc. 赞助。2019年9月22-26日;法国尼斯。资助致谢:本研究由 Neurocrine Biosciences, Inc. 赞助。
更新日期:2020-04-24
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