背景:Deutrabenazine被批准用于患有迟发性运动障碍(TD)的成年人。基于潜在精神病和基线多巴胺受体拮抗剂(DRA)使用的数据有限。
方法:完成父母研究ARM-TD或AIM-TD的TD患者符合3年的条件,开放标签扩展研究(RIM-TD;NCT02198794)。在RIM-TD中,根据运动障碍的控制和耐受性对deutrabenazine进行滴定。在对RIM-TD的事后分析中,在母体研究基线时,通过基础条件和DRA使用分析了总运动异常非自愿运动量表(AIMS)评分和不良事件(AE).
结果:在参加RIM-TD的343名患者中,336项被包括在按基本条件进行的分析中,通过使用DRA分析包括337例。205名精神病患者(精神分裂症/分裂情感障碍)中的一百八十九名(92%)和131名情绪和其他疾病(抑郁症/双相情感障碍/其他)中的65名(50%)正在接受DRA。第145周的平均(SE)德丁苯那嗪剂量为40.4(1.13),38.5(1.21),39.9(1.00),精神病患者为38.5(1.48)mg/d,那些有情绪和其他疾病的人,以及那些是否接受DRAs的人,分别。从本研究基线到第145周,总运动AIMS评分的平均值(SD)变化为-6.3(4.53),-7.1(4.92),-6.1(4.42),和-7.5(5.19)。暴露调整后的不良事件发生率(不良事件数/患者年)各组相似:任何(1.02、1.71、1.08、1.97),严重(0.10,0.12,0.10,0.12),并导致停药(0.07,0.05,0.06,0.05)。
结论:长期治疗对TD相关运动提供了有临床意义的改善,具有良好的利益-风险状况,无论基础条件或DRA使用如何。
BACKGROUND: Deutetrabenazine is approved for adults with tardive dyskinesia (TD). Data based on underlying psychiatric condition and baseline dopamine receptor antagonist (DRA) use are limited.
METHODS: Patients with TD who completed parent studies ARM-TD or AIM-TD were eligible for the 3-year, open-label extension
study (RIM-TD; NCT02198794). In RIM-TD, deutetrabenazine was titrated based on dyskinesia control and tolerability. In this post hoc analysis of RIM-TD, total motor Abnormal Involuntary Movement Scale (AIMS) score and adverse events (AEs) were analyzed by underlying condition and DRA use at parent
study baseline.
RESULTS: Of 343 patients enrolled in RIM-TD, 336 were included in the analysis by underlying condition, and 337 were included in the analysis by DRA use. One hundred eighty-nine of 205 (92%) patients with psychotic disorders (schizophrenia/schizoaffective disorder) and 65 of 131 (50%) with mood and other disorders (depression/bipolar disorder/other) were receiving a DRA. Mean (SE) deutetrabenazine doses at week 145 were 40.4 (1.13), 38.5 (1.21), 39.9 (1.00), and 38.5 (1.48) mg/d for patients with psychotic disorders, those with mood and other disorders, and those receiving DRAs or not, respectively. Mean (SD) changes in total motor AIMS score from this
study baseline to week 145 were -6.3 (4.53), -7.1 (4.92), -6.1 (4.42), and -7.5 (5.19). Exposure-adjusted incidence rates (number of AEs/patient-years) of AEs were similar across groups: any (1.02, 1.71, 1.08, 1.97), serious (0.10, 0.12, 0.10, 0.12), and leading to discontinuation (0.07, 0.05, 0.06, 0.05).
CONCLUSIONS: Long-term deutetrabenazine provided clinically meaningful improvements in TD-related movements, with a favorable benefit-risk profile, regardless of underlying condition or DRA use.