Vlachopoulou Katerina, Tutein Nolthenius Joanne, Luscombe Jo, Radford Jessica, Haria Keval, Bolan Faye, Bah Sirah
Pharming Group N.V., Leiden, The Netherlands.
MAP Patient Access Limited, Cambridge, UK.
BMC Immunol. 2025 Jul 19;26(1):52. doi: 10.1186/s12865-025-00723-6.
Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an ultra-rare inborn error of immunity, characterised by immunodeficiency and immune dysregulation. Having only been recognised in 2013, evidence on APDS is limited. We carried out four systematic literature reviews (SLRs) to identify and narratively synthesise evidence on the following for APDS: epidemiology (epidemiology SLR), clinical efficacy/safety of treatments (clinical SLR), cost-effectiveness and costs/healthcare (HCRU) associated with (economic SLR) and health-related quality of life (HRQoL) and utility data (HRQoL SLR) from a global perspective.
The Cochrane Collaboration and the University of York's Centre for Reviews and Dissemination (CRD) guidelines were followed. MEDLINE, Embase, the Cochrane Library, University of York CRD, conference proceedings and other grey literature were searched through to May 2023 for all SLRs, except the epidemiology SLR (searched to Nov 2021); economic databases were also searched for the economic and HRQoL SLRs. Eligible records were: primary epidemiology publications (epidemiology SLR), interventional/observational studies of treatments (clinical SLR), cost/HCRU studies/economic evaluations (economic SLR) and HRQoL/utility studies (HRQoL SLR) in people with APDS. Risk of bias was assessed using the Downs and Black checklist (clinical SLR) and the Drummond checklist (economic SLR).
The numbers of unique relevant studies identified were: 0 (epidemiology SLR), 117 (clinical SLR; 87 reported on <5 patients), 2 (economic SLR) and 1 (HRQoL SLR). The clinical SLR reported symptomatic treatments to be only partially effective at controlling APDS manifestations, with variable tolerability. Outcome reporting was heterogeneous and inconsistent, with small sample sizes and patients receiving multiple treatments, limiting interpretation of results. The economic SLR reported a high direct cost of APDS. Additional HRQoL/utility studies are required to evaluate the clinical and HRQoL burden of APDS and the impact of therapies.
Four methodologically robust SLRs identified limited evidence on epidemiology, clinical outcomes, costs and HRQoL in APDS, reflecting its ultra-rare nature and recent recognition. This suggests a need for more rigorous data evaluating the clinical and economic effectiveness of APDS treatments. Outcome reporting was highly heterogeneous and inconsistent across studies, sample sizes were small and patients often received multiple treatments, limiting interpretation of results.
活化磷脂酰肌醇3激酶δ（PI3Kδ）综合征（APDS）是一种极为罕见的先天性免疫缺陷病，其特征为免疫缺陷和免疫失调。APDS直到2013年才被认识，相关证据有限。我们进行了四项系统文献综述（SLR），以识别并叙述性综合关于APDS以下方面的证据：流行病学（流行病学SLR）、治疗的临床疗效/安全性（临床SLR）、成本效益以及与之相关的成本/医疗保健利用（HCRU）（经济SLR），以及从全球视角出发的健康相关生活质量（HRQoL）和效用数据（HRQoL SLR）。
遵循Cochrane协作网和约克大学评审与传播中心（CRD）的指南。除流行病学SLR（检索至2021年11月）外，对MEDLINE、Embase、Cochrane图书馆、约克大学CRD、会议论文集及其他灰色文献进行检索，截至2023年5月用于所有SLR；还对经济数据库进行检索以用于经济和HRQoL SLR。符合条件的记录包括：原发性流行病学出版物（流行病学SLR）、治疗的干预性/观察性研究（临床SLR）、成本/HCRU研究/经济评估（经济SLR）以及APDS患者的HRQoL/效用研究（HRQoL SLR）。使用唐斯和布莱克清单（临床SLR）以及德拉蒙德清单（经济SLR）评估偏倚风险。
所识别的独特相关研究数量分别为：0（流行病学SLR）、117（临床SLR；87项报告的患者少于5例）、2（经济SLR）和1（HRQoL SLR）。临床SLR报告称，对症治疗在控制APDS表现方面仅部分有效，耐受性各异。结果报告存在异质性且不一致，样本量小且患者接受多种治疗，限制了结果的解释。经济SLR报告称APDS的直接成本很高。需要更多的HRQoL/效用研究来评估APDS的临床和HRQoL负担以及治疗的影响。
四项方法学严谨的SLR发现，关于APDS的流行病学、临床结果、成本和HRQoL的证据有限，这反映了其极为罕见的性质以及近期才被认识。这表明需要更严格的数据来评估APDS治疗的临床和经济有效性。各研究的结果报告高度异质性且不一致，样本量小且患者常接受多种治疗，限制了结果的解释。
