Clinical Movement Disorders Fellow, The Mount Sinai Hospital, New York, NY, USA.
Neurology and Neurosurgery, Movement Disorders Neuromodulation & Brain Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Expert Rev Neurother. 2024 Sep;24(9):849-863. doi: 10.1080/14737175.2024.2376107. Epub 2024 Jul 9.
Tardive dyskinesia (TD) and Huntington's disease (HD)-associated chorea are persistent and disabling hyperkinetic disorders that can be treated with vesicular monoamine transporter type 2 (VMAT2) inhibitors, including the recently approved once-daily (QD) formulation of deutetrabenazine (DTBZ ER). While its efficacy and safety profile have not been directly investigated, currently available data confirms bioequivalence and similar bioavailability to the twice-daily formulation (DTBZ BID).
The authors briefly review the pivotal trials establishing efficacy of DTBZ for TD and HD-associated chorea, the pharmacokinetic data for bioequivalence between QD and BID dosing of DTBZ, as well as dose proportionality evidence, titration recommendations, and safety profile for DTBZ ER.
Long-term data show that DTBZ is efficacious and well tolerated for the treatment of TD and HD-associated chorea. DTBZ ER likely demonstrates therapeutic equivalence with no new safety signals. Due to the lack of comparative clinical trial data, no evidence-based recommendation about choice of VMAT2 inhibitor or switching between VMAT2 inhibitors can be made about best practice. Ultimately, QD dosing may offer the chance of improved medication adherence, an important consideration in patients with complex treatment regimens and/or patients with cognitive decline.
迟发性运动障碍（TD）和亨廷顿病（HD）相关舞蹈病是持续性和致残性的运动障碍，可以用囊泡单胺转运体 2（VMAT2）抑制剂治疗，包括最近批准的每日一次（QD）剂型的曲替拉嗪（DTBZ ER）。虽然其疗效和安全性特征尚未直接研究，但目前可用的数据证实了 QD 和 BID 剂型之间的生物等效性和相似的生物利用度。
作者简要回顾了确立 DTBZ 对 TD 和 HD 相关舞蹈病疗效的关键性试验、QD 和 BID 剂量 DTBZ 的药代动力学数据的生物等效性，以及剂量比例证据、滴定建议和 DTBZ ER 的安全性概况。
长期数据表明，DTBZ 治疗 TD 和 HD 相关舞蹈病是有效且耐受良好的。DTBZ ER 可能表现出与无新安全信号的治疗等效性。由于缺乏比较临床试验数据，关于 VMAT2 抑制剂的选择或 VMAT2 抑制剂之间的转换，无法就最佳实践提出循证建议。最终，QD 给药可能有机会改善药物依从性，这在治疗方案复杂的患者和/或认知能力下降的患者中是一个重要的考虑因素。
