Di Bona Danilo, Carlucci Palma, Spataro Federico, Paoletti Giovanni, Cognet-Sicé Josiane, Scurati Silvia, Canonica Giorgio Walter
Department of Precision and Regenerative Medicine and Jonic Area, Unit of Allergology, University of Bari Aldo Moro, Bari, Italy.
Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy.
J Allergy Clin Immunol Glob. 2024 Jan 9;3(2):100208. doi: 10.1016/j.jacig.2024.100208. eCollection 2024 May.
Although randomized controlled trials (RCT) are the reference standard of evidence in allergen immunotherapy (AIT), nonrandomized studies (NRS) are needed to confirm their results in more representative populations, particularly for treatment duration and persistence. However, when discrepancies are observed between RCT and NRS, NRS reliability decreases because these discrepant results are generally attributed to the methodologic flaws of NRS.
We compared the benefit of sublingual AIT (SLIT) for allergic rhinoconjunctivitis in NRS versus RCT focusing on a single product/allergen to reduce heterogeneity.
For meta-analysis, house dust mite (HDM) SLIT liquid formulation studies were sourced from computerized (Medline, Web of Science, and LILACS databases, to January 2023) and manual literature searches. Populations, treatments, and outcome data were combined (DerSimonian-Laird method). Noncomparative NRS were compared to RCT' SLIT arm before and after treatment. Efficacy was determined as the standardized mean difference (SMD) in symptom score (SS) and medication score (MS).
Data from 12 NRS (682 patients) and 8 RCT (176 patients) were analyzed. The benefit with index of reactivity (IR)-HDM SLIT liquid formulation was found significant for, first, SS in both NRS (SMD = -1.27; 95% confidence interval [CI], -1.64, -0.90) and RCT (SMD = -0.56; 95% CI, -0.90, -0.21), and second, MS with SMD equal to -1.35 (95% CI, -1.77, -0.93) and -0.46 (95% CI, -0.67, -0.25), respectively. Metaregression showed that symptom improvement was correlated with treatment duration with consistent results in NRS and RCT with 12-month SS data: -0.87 (interquartile range, -1.02, -0.77) and -0.75 (interquartile range, -0.93, -0.41), respectively.
This meta-analysis showed comparable clinical benefit of IR-HDM SLIT liquid formulation increasing over time in both NRS and RCT, suggesting that NRS may reliably integrate RCT results and be considered for guidelines.
尽管随机对照试验（RCT）是变应原免疫疗法（AIT）证据的参考标准，但仍需要非随机研究（NRS）来在更具代表性的人群中证实其结果，特别是在治疗持续时间和持续性方面。然而，当观察到RCT和NRS之间存在差异时，NRS的可靠性会降低，因为这些差异结果通常归因于NRS的方法学缺陷。
我们比较了NRS与RCT中舌下AIT（SLIT）治疗变应性鼻结膜炎的益处，重点关注单一产品/变应原以减少异质性。
为进行荟萃分析，屋尘螨（HDM）SLIT液体制剂研究来自计算机检索（截至2023年1月的Medline、科学网和LILACS数据库）和手工文献检索。合并人群、治疗和结局数据（DerSimonian-Laird方法）。将非对照NRS与RCT的SLIT组在治疗前后进行比较。疗效以症状评分（SS）和药物评分（MS）的标准化均值差（SMD）来确定。
分析了12项NRS（682例患者）和8项RCT（176例患者）的数据。发现反应性指数（IR）-HDM SLIT液体制剂的益处显著，首先，在NRS（SMD = -1.27；95%置信区间[CI]，-1.64，-0.90）和RCT（SMD = -0.56；95%CI，-0.90，-0.21）中SS均有改善；其次，MS的SMD分别等于-1.35（95%CI，-1.77，-0.93）和-0.46（95%CI, -0.67, -0.25）。Meta回归显示症状改善与治疗持续时间相关，在NRS和RCT中12个月SS数据的结果一致：分别为-0.87（四分位间距，-1.02，-0.77）和-0.75（四分位间距，-0.93，-0.41）。
这项荟萃分析表明，IR-HDM SLIT液体制剂在NRS和RCT中随时间推移具有相当的临床益处，这表明NRS可能可靠地整合RCT结果并可用于指南制定。
