■治疗抵抗性抑郁症(TRD)影响10-30%的重度抑郁症患者。在4周的试验中,艾氯胺酮鼻喷雾剂(NS)有效vs.安慰剂时,除了新的选择性5-羟色胺或5-羟色胺去甲肾上腺素再摄取抑制剂外,还开始使用。然而,缺乏与真实世界治疗(RWT)的扩展范围的比较。
■ICEBERG是使用基于倾向评分的逆概率加权的调整间接治疗比较,对接受esketamineNS加来自SUSTAIN-2(NCT02497287;clinicaltrials.gov)研究的口服抗抑郁药的患者的6个月反应和缓解数据进行了研究,与从欧洲观察性TRD队列(EOTC;NCT03373253;clinicaltrials.gov)研究中接受其他RWT的患者进行比较。SUSTAIN-2是一项关于艾氯胺酮NS的长期开放标签研究,而EOTC是在艾氯胺酮NS不能作为RWT时进行的。进行阈值和敏感性分析以评估主要分析的稳健性。
■接受esketamineNS的患者6个月反应(49.7%[95%置信区间(CI)45.6-53.9])和缓解(33.6%[95%CI29.7-37.6])的概率较高。接受RWT的患者(26.4%[95%CI21.5-31.4]和18.2%[95%CI13.9-22.5],分别),根据治疗估计中重新调整的平均治疗效果。在6个月的反应中,所产生的调整后优势比(OR)和相对风险(RR)倾向于使用esketamineNS而不是RWT(OR2.756[95%CI2.034-3.733],p<0.0001;RR1.882[95%CI1.534-2.310],p<0.0001)和缓解(OR2.276[95%CI1.621-3.196],p<0.0001;RR1.847[95%CI1.418-2.406],p<0.0001)。阈值分析表明,这两项研究之间的差异是稳健的,在广泛的敏感性分析中,结果是一致的。
■ICEBERG支持,6个月时,对于TRD患者,艾氯胺酮NS比RWT具有实质性和显着的益处。虽然结果可能会受到未观察到的混杂因素的影响,阈值分析表明,这些不太可能影响研究结论.要查看此出版物的动画摘要,请点击补充视频。
UNASSIGNED: Treatment resistant depression (TRD) affects 10-30% of patients with major depressive disorder. In 4-week trials, esketamine nasal spray (NS) was efficacious vs. placebo when both were initiated in addition to a new selective serotonin or serotonin norepinephrine reuptake inhibitor. However, comparison with an extended range of real-world treatments (RWT) is lacking.
UNASSIGNED: ICEBERG was an adjusted indirect treatment comparison using propensity score-based inverse probability weighting, performed on 6-month response and remission data from patients receiving esketamine NS plus oral antidepressant from the SUSTAIN-2 (NCT02497287; clinicaltrials.gov)
study, compared with patients receiving other RWT from the European Observational TRD Cohort (EOTC; NCT03373253; clinicaltrials.gov)
study. SUSTAIN-2 was a long-term open-label
study of esketamine NS, while the EOTC was conducted at a time when esketamine NS was not available as RWT. Threshold and sensitivity analyses were conducted to assess how robust the primary analyses were.
UNASSIGNED: Patients receiving esketamine NS had 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]) vs. patients receiving RWT (26.4% [95% CI 21.5-31.4] and 18.2% [95% CI 13.9-22.5], respectively), according to rescaled average treatment effect among treated estimates. Resulting adjusted odds ratios (OR) and relative risk (RR) favoured esketamine NS over RWT for 6-month response (OR 2.756 [95% CI 2.034-3.733], p < 0.0001; RR 1.882 [95% CI 1.534-2.310], p < 0.0001) and remission (OR 2.276 [95% CI 1.621-3.196], p < 0.0001; RR 1.847 [95% CI 1.418-2.406], p < 0.0001). Threshold analyses suggested that differences between the two studies were robust, and results were consistent across extensive sensitivity analyses.
UNASSIGNED: ICEBERG supports that, at 6 months, esketamine NS has a substantial and significant benefit over RWT for patients with TRD. While results may be affected by unobserved confounding factors, threshold analyses suggested these were unlikely to impact the
study conclusions.To view an animated summary of this publication, please click on the Supplementary video.