Background

Long-acting injectable (LAI) antipsychotics, compared with oral antipsychotics (OA), have been found to significantly improve patient outcomes, including reduced hospitalizations and emergency room (ER) admissions and increased medication adherence among adult patients with schizophrenia. In turn, the clinical benefits achieved may translate into lower economic burden. Real-world evidence of the comparative effectiveness of LAI is needed to understand the potential benefits of LAI outside of the context of clinical trials. This study aimed to provide a comprehensive synthesis of recent published real-world studies comparing healthcare utilization, costs, and adherence between patients with schizophrenia treated with LAI versus OA in the United States.

Methods

In this systematic literature review, MEDLINE^® was searched for peer-reviewed, real-world studies (i.e., retrospective or pragmatic designs) published in English between January 1, 2010 and February 10, 2020. Comparative studies reporting hospitalizations, ER admissions, healthcare costs, or medication adherence (measured by proportion of days covered [PDC]) in adults with schizophrenia treated with LAI versus OA (or pre- vs post-LAI initiation) in the United States were retained. Random effects meta-analyses were conducted among eligible studies to evaluate the association of LAI versus OA use on hospitalizations, ER admissions, healthcare costs, and treatment adherence. A sensitivity analysis among the subset of studies that compared OA with paliperidone palmitate once monthly (PP1M), specifically, was conducted.

Results

A total of 1083 articles were identified by the electronic literature search, and two publications were manually added subsequently. Among the 57 publications meeting the inclusion criteria, 25 provided sufficient information for inclusion in the meta-analyses. Compared with patients treated with OA, patients initiated on LAI had lower odds of hospitalization (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.54–0.71, n = 7), fewer hospitalizations (incidence rate ratio [IRR] [95% CI] 0.75 [0.65–0.88], n = 9), and fewer ER admissions (IRR [95% CI] 0.86 [0.77–0.97], n = 6). The initiation of LAI was associated with higher per-patient-per-year (PPPY) pharmacy costs (mean difference [MD] [95% CI] $5603 [3799–7407], n = 6), which was offset by lower PPPY medical costs (MD [95% CI] − $5404 [− 7745 to − 3064], n = 6), resulting in no significant net difference in PPPY total all-cause healthcare costs between patients treated with LAI and those treated with OA (MD [95% CI] $327 [− 1565 to 2219], n = 7). Patients initiated on LAI also had higher odds of being adherent to their medication (PDC ≥ 80%; OR [95% CI] 1.89 [1.52–2.35], n = 9). A sensitivity analysis on a subset of publications evaluating PP1M found results similar to those of the main analysis conducted at the LAI class level.

Conclusions

Based on multiple studies with varying sub-types of patient populations with schizophrenia in the United States published in the last decade, this meta-analysis demonstrated that LAI antipsychotics were associated with improved medication adherence and significant clinical benefit such as reduced hospitalizations and ER admissions compared with OA. The lower medical costs offset the higher pharmacy costs, resulting in a non-significant difference in total healthcare costs. Taken together, these findings provide strong evidence on the clinical and economic benefits of LAI compared with OA for the treatment of schizophrenia in the real world.

中文翻译：

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美国精神分裂症患者中长效注射剂与口服抗精神病药临床和经济影响的真实证据：系统评价和荟萃分析

背景

与口服抗精神病药 (OA) 相比，长效注射 (LAI) 抗精神病药已被发现可显着改善患者预后，包括减少住院和急诊室 (ER) 入院，以及提高成年精神分裂症患者的药物依从性。反过来，所获得的临床益处可能会转化为较低的经济负担。需要 LAI 比较有效性的真实世界证据来了解 LAI 在临床试验范围之外的潜在益处。本研究旨在全面综合最近发表的真实世界研究，比较美国接受 LAI 与 OA 治疗的精神分裂症患者的医疗保健利用率、成本和依从性。

方法

在这篇系统的文献综述中，MEDLINE ^®检索了 2010 年 1 月 1 日至 2020 年 2 月 10 日期间以英文发表的经同行评议的真实世界研究（即回顾性或实用设计）。在美国接受 LAI 与 OA（或 LAI 启动前与后）治疗的精神分裂症成人患者的覆盖天数比例 [PDC]）被保留。在符合条件的研究中进行了随机效应荟萃分析，以评估 LAI 与 OA 使用对住院、急诊室入院、医疗保健费用和治疗依从性的关联。具体而言，对 OA 与棕榈酸帕利哌酮每月一次 (PP1M) 进行比较的研究子集进行了敏感性分析。

结果

通过电子文献检索共识别出1083篇文章，随后手动添加了2篇出版物。在符合纳入标准的 57 篇出版物中，有 25 篇为纳入荟萃分析提供了足够的信息。与接受 OA 治疗的患者相比，开始接受 LAI 治疗的患者住院几率更低（优势比 [OR] 0.62，95% 置信区间 [CI] 0.54–0.71，n = 7），更少的住院率（发生率比 [IRR] [ 95% CI] 0.75 [0.65–0.88], n = 9)，以及更少的 ER 入院 (IRR [95% CI] 0.86 [0.77–0.97], n = 6)。LAI 的启动与较高的每位患者每年 (PPPY) 药房成本相关（平均差 [MD] [95% CI] $5603 [3799–7407]，n= 6），这被较低的 PPPY 医疗费用所抵消（MD [95% CI] - 5404 美元 [- 7745 至 - 3064]，n = 6），导致患者之间的 PPPY 总全因医疗保健费用没有显着净差异接受 LAI 治疗和接受 OA 治疗的患者 (MD [95% CI] $327 [− 1565 to 2219], n = 7)。开始使用 LAI 的患者坚持服药的几率也更高（PDC ≥ 80%；OR [95% CI] 1.89 [1.52–2.35]，n = 9）。对评估 PP1M 的出版物子集的敏感性分析发现结果与在 LAI 类级别进行的主要分析相似。

结论

基于过去十年发表的针对美国不同亚型精神分裂症患者群体的多项研究，这项荟萃分析表明，LAI 抗精神病药物与改善药物依从性和显着临床益处相关，例如减少住院和急诊入院与OA。较低的医疗成本抵消了较高的药房成本，导致总医疗成本的差异不显着。总之，这些发现为现实世界中 LAI 与 OA 治疗精神分裂症相比的临床和经济效益提供了强有力的证据。