占诺美林与氯化曲司氯铵对比安慰剂治疗精神分裂症：治疗所需人数、伤害所需人数以及受助或受伤害可能性的事后分析

Xanomeline and Trospium Chloride Versus Placebo for the Treatment of Schizophrenia: A Post Hoc Analysis of Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed.

作者信息

Citrome Leslie, Neugebauer Nichole M, Meli Alicia A, Kando Judith

机构信息

Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY, USA.

Medical Affairs, Bristol Myers Squibb, Princeton, NJ, USA.

出版信息

Neuropsychiatr Dis Treat. 2025 Apr 5;21:761-773. doi: 10.2147/NDT.S503494. eCollection 2025.

DOI:10.2147/NDT.S503494

PMID:40212458

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11981872/

Abstract

PURPOSE

Describe xanomeline and trospium chloride efficacy and safety/tolerability for the treatment of schizophrenia using number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).

METHODS

Categorical data were extracted from the three 5-week, randomized, double blind, placebo controlled EMERGENT-1, EMERGENT-2, and EMERGENT-3 clinical trials of xanomeline/trospium in adults with schizophrenia experiencing acute psychosis. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity (CGI-S), and categorical response criteria. Safety and tolerability were assessed using rates of discontinuation and treatment-emergent adverse events (TEAEs). NNT, NNH, and LHH values were calculated for each individual study as well as pooled.

RESULTS

In data from the acute EMERGENT trials, NNT estimates were significant for xanomeline/trospium vs placebo for the pre-specified treatment response threshold of ≥30% reduction from baseline in PANSS total score at Week 5 (NNT=5 [95% CI, 4-8]). NNT estimates for response thresholds of ≥20% and ≥40% reduction from baseline in PANSS total score and ≥1- and ≥2-point decrease from baseline in CGI-S score were <10, indicating a clinically relevant therapeutic benefit of xanomeline/trospium over placebo. Estimates of NNH vs placebo for the most common TEAEs were >10, with the exception of nausea and vomiting; however, rates of discontinuations due to TEAEs of nausea, dyspepsia, or vomiting were low (NNH=49 [95% CI, 28-182]). LHH indicated an overall benefit of xanomeline/trospium vs placebo for all assessed outcomes. In indirect comparisons based on published data from trials of available antipsychotics approved for schizophrenia, xanomeline/trospium exhibited comparable or more robust NNT estimates vs placebo and was the least likely agent to be associated with weight gain or somnolence/sedation.

CONCLUSION

In the 5-week EMERGENT clinical trials, NNT, NNH, and LHH assessments demonstrated a favorable benefit-risk profile for xanomeline/trospium.

TRIAL REGISTRATION

ClinicalTrials.gov identifiers: NCT03697252, NCT04659161, NCT04738123.

摘要

目的

使用治疗所需人数（NNT）、伤害所需人数（NNH）以及获益或伤害可能性（LHH）来描述 xanomeline 和氯化曲司氯铵治疗精神分裂症的疗效及安全性/耐受性。

方法

从三项为期 5 周的随机、双盲、安慰剂对照的 EMERGENT - 1、EMERGENT - 2 和 EMERGENT - 3 临床试验中提取分类数据，这些试验针对患有急性精神病的成年精神分裂症患者使用 xanomeline/曲司氯铵。疗效通过阳性和阴性症状量表（PANSS）、临床总体印象 - 严重程度（CGI - S）以及分类反应标准进行评估。安全性和耐受性通过停药率和治疗中出现的不良事件（TEAE）进行评估。计算每项单独研究以及汇总后的 NNT、NNH 和 LHH 值。

结果

在急性 EMERGENT 试验的数据中，对于预先设定的治疗反应阈值，即第 5 周时 PANSS 总分较基线降低≥30%，xanomeline/曲司氯铵与安慰剂相比，NNT 估计值具有统计学意义（NNT = 5 [95%CI，4 - 8]）。对于 PANSS 总分较基线降低≥20%和≥40%以及 CGI - S 评分较基线降低≥1 分和≥2 分的反应阈值，NNT 估计值<10，表明 xanomeline/曲司氯铵相对于安慰剂具有临床相关的治疗益处。与安慰剂相比，除恶心和呕吐外，最常见 TEAE 的 NNH 估计值>10；然而，因恶心、消化不良或呕吐等 TEAE 导致的停药率较低（NNH = 49 [95%CI，28 - 182]）。LHH 表明对于所有评估结果，xanomeline/曲司氯铵相对于安慰剂总体上具有益处。在基于已发表的精神分裂症获批抗精神病药物试验数据的间接比较中，xanomeline/曲司氯铵与安慰剂相比，显示出相当或更强的 NNT 估计值，并且是与体重增加或嗜睡/镇静相关性最小的药物。