全身型重症肌无力的加重与危象：美国的预测因素及相关经济负担

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中文摘要

引言： 全身型重症肌无力（gMG）患者加重与危象（临床事件）的管理属于资源密集型。识别与这些事件风险增加相关的特征可能有助于优化预防策略的分配。本研究识别诊断后首次临床事件的基线预测因素，并评估美国gMG患者中这些事件的负担。
方法： 从Komodo Research Database（2017年1月至2023年9月）中识别新诊断的成人gMG队列，索引日期为神经科医生首次作出gMG诊断之日。描述基线人口学特征、合并症、gMG相关治疗、医疗资源利用（HRU）和费用；随访患者直至首次临床事件或末次随访删失。采用多变量Cox比例风险模型评估首次临床事件的基线预测因素。在随访≥12个月的患者中，建立随访期间有和无临床事件的队列；索引日期分别为首次临床事件或随机日期。使用熵平衡对队列重新加权。比较索引后12个月内的HRU和费用。
结果： 在6,195例gMG患者中（平均年龄61.1岁；女性49.1%），事件风险较高与使用免疫球蛋白[风险比（HR）=1.54]、基线构音障碍（HR=1.45）、全身及其他肌肉特异性无力（HR=1.38）、使用非甾体免疫抑制剂（HR=1.37）、吞咽困难（HR=1.28）、体重下降（HR=1.27）、呼吸困难（HR=1.23）、上睑下垂（HR=1.20）、无其他自身免疫性疾病（HR=1.18）和男性（HR=1.15；均p<0.05）相关。队列中2,657例发生临床事件，3,092例未发生；所有患者索引后随访均≥12个月。重新加权后，发生临床事件的患者在索引后12个月内住院次数[率比（RR）=6.02]、急诊就诊（RR=1.91）和门诊就诊（RR=1.58；均p<0.05）更高。发生临床事件患者的平均总医疗费用高70,792美元（95,821美元 vs. 25,029美元，p<0.001），主要由免疫球蛋白和住院费用驱动。
讨论： 疾病严重程度和免疫抑制治疗使用与加重和危象风险增加相关，并造成显著的HRU和费用负担。研究结果可能有助于识别可从更早或更先进治疗中获益以预防急性临床事件的患者。

英文摘要

INTRODUCTION: The management of exacerbations and crises (clinical events) in generalized myasthenia gravis (gMG) patients is resource-intensive. Identifying characteristics associated with increased risk for these events may help optimize allocation of preventative strategies. This study identified baseline predictors of a first clinical event following diagnosis and assessed the burden of these events among patients with gMG in the United States.
METHODS: A newly diagnosed cohort of adults with gMG were identified from Komodo Research Database (01/2017-09/2023) with an index date at the first gMG diagnosis made by a neurologist. Baseline demographics, comorbidities, gMG-related treatments, healthcare resource utilization (HRU) and costs were described; patients were followed until first clinical event or censoring at end of follow-up. A multivariable Cox proportional hazards model assessed baseline predictors of the first clinical event. Among patients with ≥12 months of follow-up, cohorts with and without a clinical event during follow-up were created; index date was the first clinical event or a random date, respectively. Cohorts were re-weighted using entropy balancing. HRU and costs during 12 months post-index were compared.
RESULTS: Among 6,195 patients with gMG (mean age: 61.1 years; female: 49.1%), higher event risk was associated with use of immunoglobulin [hazard ratio (HR) = 1.54], baseline dysarthria (HR = 1.45), general and other muscle-specific weaknesses (HR = 1.38), use of non-steroidal immunosuppressants (HR = 1.37), dysphagia (HR = 1.28), weight loss (HR=1.27), dyspnea (HR = 1.23), ptosis (HR = 1.20), absence of other autoimmune disorders (HR=1.18), and male sex (HR = 1.15; all p < 0.05). In the cohort, 2,657 had a clinical event, while 3,092 did not; all had ≥12 months of follow-up after index. After re-weighting, patients with a clinical event had higher number of inpatient admissions [rate ratio (RR) = 6.02], emergency visits (RR = 1.91), and outpatient visits (RR = 1.58; all p < 0.05) in the 12 months post-index. Mean total healthcare costs were $70,792 higher among patients with a clinical event ($95,821 vs. $25,029, p < 0.001), driven by immunoglobulin and inpatient costs.
DISCUSSION: Disease severity and immunosuppressive therapy use were associated with increased risk of exacerbations and crises, which imposed substantial HRU and cost burden. Findings may help identify candidates who could benefit from earlier or more advanced therapies to prevent acute clinical events.