氟西汀作为急性弛缓性脊髓炎抗病毒药物的安全性、耐受性和疗效。
Safety, tolerability, and efficacy of fluoxetine as an antiviral for acute flaccid myelitis.
机构信息
From the Departments of Pediatrics (K.M., J.A.M., T.S., M.J.A., S.R.D.) and Neurology (K.M., S.S., J.A.M., T.S., K.L.T.), University of Colorado School of Medicine; Children's Hospital Colorado (K.M., A.L.H., J.A.M., T.S., M.J.A., S.R.D.), Aurora; Children's Hospital of Philadelphia (S.E.H.), PA; Seattle Children's Hospital (C.O.), University of Washington; Boston Children's Hospital (M.W.-M., L.A.B., M.P.G.), MA; Children's Hospital of Los Angeles (B.W., J.D.), CA; Stanford University (J.D.S., K.V.H.), Palo Alto, CA; University of California San Diego (A.T., A.H.T.); Phoenix Children's Hospital (H.K.B., M.C.K.), AZ; Boston Medical Center (A.T.), MA; Naval Medical Center of San Diego (L.Z.), CA; Departments of Pediatrics (J.R.G., N.M.) and Neurology (N.M.), Yale School of Medicine, New Haven, CT; and Children's National Medical Center (R.L.D.), Washington, DC.
出版信息
Neurology. 2019 Apr 30;92(18):e2118-e2126. doi: 10.1212/WNL.0000000000006670. Epub 2018 Nov 9.
OBJECTIVE
To determine the safety, tolerability, and efficacy of fluoxetine for proven or presumptive enterovirus (EV) D68-associated acute flaccid myelitis (AFM).
METHODS
A multicenter cohort study of US patients with AFM in 2015-2016 compared serious adverse events (SAEs), adverse effects, and outcomes between fluoxetine-treated patients and untreated controls. Fluoxetine was administered at the discretion of treating providers with data gathered retrospectively. The primary outcome was change in summative limb strength score (SLSS; sum of Medical Research Council strength in all 4 limbs, ranging from 20 [normal strength] to 0 [complete quadriparesis]) between initial examination and latest follow-up, with increased SLSS reflecting improvement and decreased SLSS reflecting worsened strength.
RESULTS
Fifty-six patients with AFM from 12 centers met study criteria. Among 30 patients exposed to fluoxetine, no SAEs were reported and adverse effect rates were similar to unexposed patients (47% vs 65%, = 0.16). The 28 patients treated with >1 dose of fluoxetine were more likely to have EV-D68 identified (57.1% vs 14.3%, < 0.001). Their SLSS was similar at initial examination (mean SLSS 12.9 vs 14.3, = 0.31) but lower at nadir (mean SLSS 9.25 vs 12.82, = 0.02) and latest follow-up (mean SLSS 12.5 vs 16.4, = 0.005) compared with the 28 patients receiving 1 (n = 2) or no (n = 26) doses. In propensity-adjusted analysis, SLSS from initial examination to latest follow-up decreased by 0.2 (95% confidence interval [CI] -1.8 to +1.4) in fluoxetine-treated patients and increased by 2.5 (95% CI +0.7 to +4.4) in untreated patients ( = 0.015).
CONCLUSION
Fluoxetine was well-tolerated. Fluoxetine was preferentially given to patients with AFM with EV-D68 identified and more severe paralysis at nadir, who ultimately had poorer long-term outcomes.
CLASSIFICATION OF EVIDENCE
This study provides Class IV evidence that for patients with EV-D68-associated AFM, fluoxetine is well-tolerated and not associated with improved neurologic outcomes.
目的
确定氟西汀治疗已证实或疑似肠道病毒（EV）D68 相关急性弛缓性脊髓炎（AFM）的安全性、耐受性和疗效。
方法
2015-2016 年，一项针对美国 AFM 患者的多中心队列研究比较了氟西汀治疗患者和未治疗对照组的严重不良事件（SAE）、不良反应和结局。氟西汀由治疗医生根据患者情况决定使用，数据通过回顾性收集。主要结局是初始检查和最近随访时总结肢体力量评分（SLSS；四肢肌力量总和，范围为 20[正常力量]至 0[完全四肢瘫痪]）的变化，SLSS 增加反映改善，SLSS 减少反映力量恶化。
结果
12 个中心的 56 名 AFM 患者符合研究标准。在 30 名接受氟西汀治疗的患者中，未报告 SAE，不良反应发生率与未暴露患者相似（47%比 65%， = 0.16）。28 名接受>1 剂氟西汀治疗的患者更有可能检测到 EV-D68（57.1%比 14.3%， < 0.001）。他们的初始检查 SLSS 相似（平均 SLSS 12.9 比 14.3， = 0.31），但最低点（平均 SLSS 9.25 比 12.82， = 0.02）和最近随访（平均 SLSS 12.5 比 16.4， = 0.005）的 SLSS 较低。与接受 1（n = 2）或未接受（n = 26）剂量的 28 名患者相比。在倾向评分调整分析中，氟西汀治疗组从初始检查到最近随访的 SLSS 下降了 0.2（95%置信区间[CI] -1.8 至 +1.4），未治疗组增加了 2.5（95% CI +0.7 至 +4.4）（ = 0.015）。
结论
氟西汀耐受性良好。氟西汀更倾向于用于 EV-D68 确诊且最低点瘫痪更严重的 AFM 患者，这些患者的长期预后更差。
证据分类
本研究提供了 IV 级证据，表明对于 EV-D68 相关 AFM 患者，氟西汀耐受良好，与改善神经结局无关。
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