PDF(Pubmed)
Abstract：
UNASSIGNED: The efficacy of esketamine nasal spray (NS) as a rapid-acting agent for treatment resistant depression (TRD) was demonstrated in comparisons with placebo, when both were given in addition to a newly initiated selective serotonin reuptake inhibitor (SSRI)/serotonin norepinephrine reuptake inhibitor (SNRI). How esketamine NS compares with commonly used real-world (RW) polypharmacy treatment strategies is not known.
UNASSIGNED: ICEBERG was an adjusted indirect treatment comparison that analysed data from SUSTAIN-2 (NCT02497287; clinicaltrials.gov), a long-term, open-label study of esketamine NS plus SSRI/SNRI, and the European Observational TRD Cohort (EOTC; NCT03373253; clinicaltrials.gov), an observational study of routine clinical practice. Data were compared between patients receiving esketamine NS (SUSTAIN-2) and those from the EOTC treated with polypharmacy treatment strategies, either combination or augmentation. Analyses were adjusted for potential confounders, using rescaled average treatment effect among treated estimates. Threshold analyses were conducted to assess potential impact of unmeasured confounders on the robustness of analyses where esketamine NS was found to be significantly superior. Sensitivity analyses were used to understand the impact of analysis method selection and data handling.
UNASSIGNED: Esketamine NS treatment resulted in a higher probability of 6-month response (49.7% [95% confidence interval (CI) 45.6-53.9]) and remission (33.6% [95% CI 29.7-37.6]) versus RW polypharmacy (26.8% [95% CI 21.0-32.5] and 19.4%, [95% CI 14.2-24.6], respectively). Relative risk calculations showed esketamine NS was 1.859 (95% CI 1.474-2.345; p < 0.0001) times as likely to result in response and 1.735 (1.297-2.322; p = 0.0002) times as likely to result in remission versus RW polypharmacy at 6 months. Threshold and extensive sensitivity analyses supported that analyses of esketamine NS superiority were robust.
UNASSIGNED: ICEBERG supports esketamine NS being superior to current RW individualized polypharmacy strategies, including augmentation, with benefits extending beyond acute use, to improved chance of 6-month response and remission. While unobserved confounding factors may certainly impact results of an indirect comparison, threshold analysis supported a low likelihood of this affecting the conclusions.To view an animated summary of this publication, please click on the Supplementary video.
UNASSIGNED: ICEBERG was an adjusted indirect treatment comparison that analysed data from SUSTAIN-2 (NCT02497287; clinicaltrials.gov), a long-term, open-label study of esketamine NS plus SSRI/SNRI, and the European Observational TRD Cohort (EOTC; NCT03373253; clinicaltrials.gov), an observational study of routine clinical practice. Data were compared between patients receiving esketamine NS (SUSTAIN-2) and those from the EOTC treated with polypharmacy treatment strategies, either combination or augmentation. Analyses were adjusted for potential confounders, using rescaled average treatment effect among treated estimates. Threshold analyses were conducted to assess potential impact of unmeasured confounders on the robustness of analyses where esketamine NS was found to be significantly superior. Sensitivity analyses were used to understand the impact of analysis method selection and data handling.
UNASSIGNED: Esketamine NS treatment resulted in a higher probability of 6-month response (49.7% [95% confidence interval (CI) 45.6-53.9]) and remission (33.6% [95% CI 29.7-37.6]) versus RW polypharmacy (26.8% [95% CI 21.0-32.5] and 19.4%, [95% CI 14.2-24.6], respectively). Relative risk calculations showed esketamine NS was 1.859 (95% CI 1.474-2.345; p < 0.0001) times as likely to result in response and 1.735 (1.297-2.322; p = 0.0002) times as likely to result in remission versus RW polypharmacy at 6 months. Threshold and extensive sensitivity analyses supported that analyses of esketamine NS superiority were robust.
UNASSIGNED: ICEBERG supports esketamine NS being superior to current RW individualized polypharmacy strategies, including augmentation, with benefits extending beyond acute use, to improved chance of 6-month response and remission. While unobserved confounding factors may certainly impact results of an indirect comparison, threshold analysis supported a low likelihood of this affecting the conclusions.To view an animated summary of this publication, please click on the Supplementary video.
摘要：
■与安慰剂相比，证明了艾氯胺酮鼻喷雾剂（NS）作为治疗难治性抑郁症（TRD）的速效药的功效，当两者都是除了新启动的选择性5-羟色胺再摄取抑制剂（SSRI）/5-羟色胺去甲肾上腺素再摄取抑制剂（SNRI）之外。艾氯胺酮NS与常用的现实世界（RW）多药物治疗策略的比较尚不清楚。
■ICEBERG是一个调整后的间接治疗比较，分析了来自SUSTAIN-2（NCT02497287；clinicaltrials.gov）的数据，一个长期的,艾氯胺酮NS加SSRI/SNRI的开放标签研究，和欧洲观察TRD队列（EOTC；NCT03373253；clinicaltrials.gov），常规临床实践的观察性研究。比较接受esketamineNS（SUSTAIN-2）的患者和接受多药物治疗策略的EOTC患者的数据。无论是组合还是增强。对潜在的混杂因素进行了分析调整，在治疗后的估计值中使用重新缩放的平均治疗效果。进行了阈值分析，以评估未测量的混杂因素对分析的稳健性的潜在影响，其中esketamineNS被发现是显著优越的。敏感性分析用于了解分析方法选择和数据处理的影响。
■EsketamineNS治疗导致6个月缓解（49.7%[95%置信区间（CI）45.6-53.9]）和缓解（33.6%[95%CI29.7-37.6]）的概率高于RW复方药（26.8%[95%CI21.0-32.5]和19.4%，[95%CI14.2-24.6]，分别)。相对风险计算显示，在6个月时，esketamineNS可能导致缓解的1.859（95％CI1.474-2.345；p<0.0001）倍，可能导致缓解的1.735（1.297-2.322；p=0.0002）倍。阈值和广泛的敏感性分析支持对esketamineNS优势的分析是稳健的。
■ICEBERG支持esketamineNS优于当前的RW个性化多药房策略，包括增强，好处超出了急性使用，改善6个月反应和缓解的机会。虽然未观察到的混杂因素肯定会影响间接比较的结果，阈值分析支持这种影响结论的可能性较低。要查看此出版物的动画摘要，请点击补充视频。
■ICEBERG是一个调整后的间接治疗比较，分析了来自SUSTAIN-2（NCT02497287；clinicaltrials.gov）的数据，一个长期的,艾氯胺酮NS加SSRI/SNRI的开放标签研究，和欧洲观察TRD队列（EOTC；NCT03373253；clinicaltrials.gov），常规临床实践的观察性研究。比较接受esketamineNS（SUSTAIN-2）的患者和接受多药物治疗策略的EOTC患者的数据。无论是组合还是增强。对潜在的混杂因素进行了分析调整，在治疗后的估计值中使用重新缩放的平均治疗效果。进行了阈值分析，以评估未测量的混杂因素对分析的稳健性的潜在影响，其中esketamineNS被发现是显著优越的。敏感性分析用于了解分析方法选择和数据处理的影响。
■EsketamineNS治疗导致6个月缓解（49.7%[95%置信区间（CI）45.6-53.9]）和缓解（33.6%[95%CI29.7-37.6]）的概率高于RW复方药（26.8%[95%CI21.0-32.5]和19.4%，[95%CI14.2-24.6]，分别)。相对风险计算显示，在6个月时，esketamineNS可能导致缓解的1.859（95％CI1.474-2.345；p<0.0001）倍，可能导致缓解的1.735（1.297-2.322；p=0.0002）倍。阈值和广泛的敏感性分析支持对esketamineNS优势的分析是稳健的。
■ICEBERG支持esketamineNS优于当前的RW个性化多药房策略，包括增强，好处超出了急性使用，改善6个月反应和缓解的机会。虽然未观察到的混杂因素肯定会影响间接比较的结果，阈值分析支持这种影响结论的可能性较低。要查看此出版物的动画摘要，请点击补充视频。
