ObjectiveTardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Long-term safety of the approved TD medication, valbenazine, was demonstrated in 2 clinical trials (KINECT 3 [NCT02274558], KINECT 4 [NCT02405091]). Data from these trials were analyzed post hoc to evaluate the onset and resolution of adverse events (AEs).MethodsParticipants in KINECT 3 and KINECT 4 received up to 48 weeks of once-daily valbenazine (40 or 80 mg). Data from these studies were pooled and analyzed to assess the incidence, time to first occurrence, and resolution for the following AEs of potential clinical interest: akathisia, balance disorder, dizziness, parkinsonism, somnolence/sedation, suicidal behavior/ideation, and tremor.ResultsIn the pooled population (N=314), all AEs of potential clinical interest occurred in <10% of participants, with somnolence (9.6%), suicidal behavior/ideation (6.4%), and dizziness (5.7%) being the most common AEs. Mean time to first occurrence ranged from 36 days (akathisia [n=9]) to 224 days (parkinsonism [n=2]). By end of study (or last study visit), resolution of AEs was as follows: 100% (suicidal ideation/behavior, parkinsonism); >85% (somnolence/sedation, dizziness); >70% (akathisia, balance disorder, tremor).ConclusionsIn long-term clinical trials, the incidence of AEs of potential clinical interest was low (<10%) and most were resolved by end of treatment (>70–100%). All patients taking valbenazine should be routinely monitored for AEs, particularly those that may exacerbate the motor symptoms associated with TD.FundingNeurocrine Biosciences, Inc.

中文翻译：

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缬苯那嗪治疗的迟发性运动障碍患者主要不良事件的发生和缓解：两项长期临床试验的汇总分析

目标迟发性运动障碍 (TD) 是一种持续性且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。2 项临床试验（KINECT 3 [NCT02274558]、KINECT 4 [NCT02405091]）证明了批准的 TD 药物缬苯那嗪的长期安全性。对这些试验的数据进行事后分析，以评估不良事件 (AE) 的发生和解决。方法 KINECT 3 和 KINECT 4 的参与者接受了长达 48 周的每日一次缬苯那嗪（40 或 80 毫克）。汇总和分析这些研究的数据，以评估以下具有潜在临床意义的不良事件的发生率、首次发生时间和解决情况：静坐不能、平衡障碍、头晕、帕金森症、嗜睡/镇静、自杀行为/意念和震颤。结果在汇总人群 (N=314) 中，所有具有潜在临床意义的 AE 发生在 <10% 的参与者中，嗜睡 (9.6%)、自杀行为/念头 (6.4%) 和头晕 (5.7%) 是最常见的不良事件。首次出现的平均时间范围从 36 天（静坐不能 [n=9]）到 224 天（帕金森氏症 [n=2]）。在研究结束（或最后一次研究访问）时，AE 的解决如下：100%（自杀意念/行为、帕金森病）；>85%（嗜睡/镇静、头晕）；>70%（静坐不能、平衡障碍、震颤）。结论在长期临床试验中，具有潜在临床意义的 AE 发生率很低（<10%），大多数在治疗结束时得到解决（>70-100%）。应常规监测所有服用缬苯那嗪的患者的 AE，尤其是那些可能加剧与 TD 相关的运动症状的 AE。