摘要
目的评价宁瘿方联合小剂量抗甲状腺药物(ATDs)对Graves甲状腺功能亢进症(GH)缓解期复发风险的影响,并分析GH复发与促甲状腺激素受体抗体(TRAb)转阴的相关因素,为GH缓解期规范化管理提供依据。方法开展单中心回顾性队列研究,纳入GH缓解期患者269例。采用倾向性评分匹配(PSM)后构建102对(204例)均衡队列,对照组接受小剂量ATDs维持治疗,暴露组在此基础上联合宁瘿方核心复方。主要结局指标为GH复发率,次要结局指标为TRAb转阴率(TRAb<1.75 IU/L),安全性指标为治疗相关不良事件。采用Cox回归模型与Kaplan-Meier曲线评估组间差异,并以逆概率加权(IPTW)进行敏感性分析。结果匹配队列中位随访28.07个月。GH复发率结局方面,暴露组复发率(18/102,17.6%)明显低于对照组(31/102,30.4%,χ^(2)=4.539,P=0.033);TRAb转阴结局方面,暴露组TRAb转阴率(50/102,49.0%)明显高于对照组(23/102,22.5%,χ^(2)=15.551,P<0.001)。复发率多因素Cox回归分析显示宁瘿方治疗可降低复发风险[HR=0.324,95%CI(0.170,0.617),P<0.001]。男性[HR=2.209,95%CI(1.079,4.520),P=0.030]、较高的初诊TRAb水平[每升高1 IU/L:HR=1.033,95%CI(1.003,1.064),P=0.032]、较大的甲状腺体积[每增加1 ml:HR=1.045,95%CI(1.003,1.088),P=0.035]为复发独立危险因素;TRAb转阴率多因素Cox回归分析提示宁瘿方治疗可促进TRAb转阴[HR=1.826,95%CI(1.091,3.056),P=0.022],而初诊TRAb的水平越高转阴概率越低[HR=0.974,95%CI(0.950,0.998),P=0.032]。暴露组复发率生存分析差异显著(Log-Rank P=0.003);TRAb结局方面生存分析差异显著(Log-Rank P=0.034)。两组治疗相关不良事件发生率相近(P=0.757)。IPTW敏感性分析与主分析一致,结果稳健。结论宁瘿方联合小剂量ATDs可显著降低GH缓解期复发风险并提高TRAb转阴率,且未增加常见不良事件,适合作为缓解期降低复发风险的可选策略。男性、较高基线TRAb及较大甲状腺体积提示更高复发风险,值得重点随访与分层管理。
Objective To evaluate the effect of Ningying Formula(宁瘿方)combined with low-dose antithyroid drugs(ATDs)on the relapse risk for patients with Graves'hyperthyroidism(GH)during the remission phase,and to analyze the related factors between GH relapse and thyrotropin receptor antibody(TRAb)negativity,so as to provide evidence for the standardized management of GH in remission stage.Methods A single-center retrospective cohort study was conducted,including 269 GH patients in the remission stage.After propensity score matching(PSM),102 matched pairs(204 patients)were established.The control group received low-dose ATDs as maintenance therapy,while the exposure group received the core Ningying Formula in addition to low-dose ATDs.The primary outcome was the GH recurrence rate;the secondary outcome was the thyrotropin receptor antibody(TRAb)negativity rate(TRAb<1.75 IU/L).Safety outcomes included treatment-related adverse events.Differences between groups were assessed using Cox regression models and Kaplan-Meier curves,with sensitivity analysis performed using inverse probability of treatment weighting(IPTW).Results The median follow-up in the matched cohort was 28.07 months.Regarding the GH recurrence outcome,the recurrence rate in the exposure group(18/102,17.6%)was significantly lower than that in the control group(31/102,30.4%;χ^(2)=4.539,P=0.033);regarding the TRAb negativity outcome,the TRAb negativity rate in the exposure group(50/102,49.0%)was significantly higher than that in the control group(23/102,22.5%;χ^(2)=15.551,P<0.001).Multivariate Cox regression analysis for recurrence showed that Ningying Formula treatment reduced the risk of recurrence[HR=0.324,95%CI(0.170,0.617),P<0.001].Male[HR=2.209,95%CI(1.079,4.520),P=0.030],higher initial TRAb level[per 1 IU/L increase:HR=1.033,95%CI(1.003,1.064),P=0.032],and larger thyroid volume[per 1 ml increase:HR=1.045,95%CI(1.003,1.088),P=0.035]were identified as independent risk factors for recurrence;multivariate Cox regression analysis for TRAb negativity indicated that Ningying Formula treatment promoted TRAb negativity[HR=1.826,95%CI(1.091,3.056),P=0.022],while a higher initial TRAb level was associated with a lower probability of negativity[HR=0.974,95%CI(0.950,0.998),P=0.032].Survival analysis showed significant differences in relapse rate between groups(Log-Rank P=0.003)and in TRAb outcomes(Log-Rank P=0.034).The incidence of treatment-related adverse events was similar between groups(P=0.757).The IPTW sensitivity analysis was consistent with the primary analysis,indicating robust results.Conclusion The Ningying Formula combined with low-dose ATDs can significantly reduce the risk of recurrence and can improve the TRAb negativity rate in GH patients during the remission stage,without increasing common adverse events,making it an optional strategy for reducing relapse risk during remission.Male gender,higher baseline TRAb level,and larger thyroid volume indicate a higher risk of recurrence,warranting focused follow-up and stratified management.
作者
黄昱钦
张明帅
刘世建
陶枫
陈易
HUANG Yuqin;ZHANG Mingshuai;LIU Shijian;TAO Feng;CHEN Yi(Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai,200071)
出处
《中医杂志》
北大核心
2026年第1期45-52,共8页
Journal of Traditional Chinese Medicine
基金
上海市嘉定区卫生健康委员会中医药科研课题(2024-KY-ZYY-05)。
