Abstract：
Objective: Aripiprazole lauroxil (AL), a long-acting injectable antipsychotic, has 2 initiation options: 1-day (AL NanoCrystal Dispersion [ALNCD] injection plus 30 mg oral aripiprazole on day 1 only) and 21-day (15 mg oral aripiprazole for 21 days). This post hoc analysis assessed the safety and tolerability of both initiation approaches.
Methods: We analyzed data from the first 4 weeks of 2 AL studies, one using the 1-day initiation regimen (conducted between November 2017 and March 2019) and the other using the 21-day initiation regimen (conducted between December 2011 and March 2014). Outcomes of interest during the matched 4-week period included the likelihood of adverse events (AEs), including those associated with discontinuation, rated as serious, or of special interest (injection site reactions [ISRs] and akathisia).
Results: The 1-day (n = 99) and 21-day (n = 415) initiation regimens had comparable rates of AEs (57.6% and 52.0%, respectively; most were mild), serious AEs (2.0% and 1.4%), and AEs leading to discontinuation (4.0% and 3.1%). The incidence of ISRs was 11.1% after the ALNCD injection (day 1) in the 1-day initiation regimen. ISR rates for the AL starting doses were 9.2% for the 1-day regimen (AL 1064 mg on day 8) and 3.9% for the 21-day regimen (AL 441 mg/882 mg on day 1). Rates of akathisia were 9.1% and 11.1% for the 1-day and 21-day regimens, respectively. One patient discontinued because of an ISR in the 21-day study, and 2 patients in the 21-day study discontinued because of akathisia. Mean changes from baseline in week 4 Positive and Negative Syndrome Scale total scores were -17.4 (1-day) and -19.5 (21-day).
Conclusions: Four-week safety and tolerability were similar following the initiation of AL with either the 1-day or 21-day regimen, supporting the utility of both initiation regimens. Engaging patients in discussions regarding options for initiating AL may help facilitate shared decision-making and personalization of treatment for patients with schizophrenia.
Trial Registration: ClinicalTrials.gov identifiers: NCT03345979 and NCT01469039.
Methods: We analyzed data from the first 4 weeks of 2 AL studies, one using the 1-day initiation regimen (conducted between November 2017 and March 2019) and the other using the 21-day initiation regimen (conducted between December 2011 and March 2014). Outcomes of interest during the matched 4-week period included the likelihood of adverse events (AEs), including those associated with discontinuation, rated as serious, or of special interest (injection site reactions [ISRs] and akathisia).
Results: The 1-day (n = 99) and 21-day (n = 415) initiation regimens had comparable rates of AEs (57.6% and 52.0%, respectively; most were mild), serious AEs (2.0% and 1.4%), and AEs leading to discontinuation (4.0% and 3.1%). The incidence of ISRs was 11.1% after the ALNCD injection (day 1) in the 1-day initiation regimen. ISR rates for the AL starting doses were 9.2% for the 1-day regimen (AL 1064 mg on day 8) and 3.9% for the 21-day regimen (AL 441 mg/882 mg on day 1). Rates of akathisia were 9.1% and 11.1% for the 1-day and 21-day regimens, respectively. One patient discontinued because of an ISR in the 21-day study, and 2 patients in the 21-day study discontinued because of akathisia. Mean changes from baseline in week 4 Positive and Negative Syndrome Scale total scores were -17.4 (1-day) and -19.5 (21-day).
Conclusions: Four-week safety and tolerability were similar following the initiation of AL with either the 1-day or 21-day regimen, supporting the utility of both initiation regimens. Engaging patients in discussions regarding options for initiating AL may help facilitate shared decision-making and personalization of treatment for patients with schizophrenia.
Trial Registration: ClinicalTrials.gov identifiers: NCT03345979 and NCT01469039.
摘要：
目标：阿立哌唑月桂酯（AL），长效注射抗精神病药,有2种起始选择：1天（仅第1天注射AL纳米晶体分散体[ALNCD]加30mg口服阿立哌唑）和21天（15mg口服阿立哌唑21天）。该事后分析评估了两种起始方法的安全性和耐受性。
方法：我们分析了2项AL研究的前4周的数据，一个使用1天起始方案(在2017年11月至2019年3月期间进行),另一个使用21天起始方案(在2011年12月至2014年3月期间进行).在匹配的4周期间感兴趣的结果包括不良事件（AE）的可能性，包括那些与停药有关的，被评为严重，或特别感兴趣的（注射部位反应[ISR]和静坐不能）。
结果：1天（n=99）和21天（n=415）起始方案的不良事件发生率相当（57.6％和52.0％，分别；大多数是温和的)，严重不良事件（2.0%和1.4%），和导致停药的不良事件（4.0%和3.1%）。在1天的初始方案中，ALNCD注射后（第1天）ISR的发生率为11.1％。1天方案的AL起始剂量的ISR率为9.2％（第8天的AL1064mg），21天方案的ISR率为3.9％（第1天的AL441mg/882mg）。1天和21天方案的静坐不能发生率分别为9.1%和11.1%，分别。在21天的研究中，一名患者因ISR而停药，21天研究中的2例患者因静坐不能终止。第4周阳性和阴性综合征量表总分从基线的平均变化为-17.4(1天)和-19.5(21天)。
结论：使用1天或21天方案开始AL治疗后，四周的安全性和耐受性相似。支持两种启动方案的效用。让患者参与有关开始AL的选择的讨论可能有助于促进精神分裂症患者的共同决策和个性化治疗。
试验注册：ClinicalTrials.gov标识符：NCT03345979和NCT01469039。
方法：我们分析了2项AL研究的前4周的数据，一个使用1天起始方案(在2017年11月至2019年3月期间进行),另一个使用21天起始方案(在2011年12月至2014年3月期间进行).在匹配的4周期间感兴趣的结果包括不良事件（AE）的可能性，包括那些与停药有关的，被评为严重，或特别感兴趣的（注射部位反应[ISR]和静坐不能）。
结果：1天（n=99）和21天（n=415）起始方案的不良事件发生率相当（57.6％和52.0％，分别；大多数是温和的)，严重不良事件（2.0%和1.4%），和导致停药的不良事件（4.0%和3.1%）。在1天的初始方案中，ALNCD注射后（第1天）ISR的发生率为11.1％。1天方案的AL起始剂量的ISR率为9.2％（第8天的AL1064mg），21天方案的ISR率为3.9％（第1天的AL441mg/882mg）。1天和21天方案的静坐不能发生率分别为9.1%和11.1%，分别。在21天的研究中，一名患者因ISR而停药，21天研究中的2例患者因静坐不能终止。第4周阳性和阴性综合征量表总分从基线的平均变化为-17.4(1天)和-19.5(21天)。
结论：使用1天或21天方案开始AL治疗后，四周的安全性和耐受性相似。支持两种启动方案的效用。让患者参与有关开始AL的选择的讨论可能有助于促进精神分裂症患者的共同决策和个性化治疗。
试验注册：ClinicalTrials.gov标识符：NCT03345979和NCT01469039。
