奥马珠单抗停药后哮喘症状再次出现与IgE水平升高和药代动力学浓度降低极为相关
2009/03/24
背景：医生探讨重症哮喘患者的临床症状改善后是否可以停止服用奥马珠单抗或减少服用剂量。
目的：在重症、持续、过敏性哮喘患者中进行随机、安慰剂对照试验，检测奥马珠单抗、游离IgE和临床结局间的关系，随后根据试验前的总IgE水平和体重进行剂量学研究。
方法：采用药代动力学—药效学结合模型计算奥马珠单抗在重症哮喘治疗中的作用研究(INNOVATE)中28周治疗期间和16周随访期间游离IgE、奥马珠单抗和总IgE水平。绘图表示与哮喘症状总分、晨间呼气流量峰值和对医生确定的对治疗有反应者和无反应者的补救性用药的平均改变间的关系。
结果：该模型将奥马珠单抗与游离IgE和总IgE水平准确的结合，使得每个患者完整的时程都得以重建。游离IgE水平被迅速抑制，低于50 ng/mL（20.8 IU/mL），尽管在临床检测稳定前有较长一段时间。治疗停止后，奥马珠单抗和游离IgE水平回复到基线水平，经过一段延迟，哮喘症状再次出现。从模型得到的奥马珠单抗和游离IgE水平与临床结局的改变极为相关，特别是对奥马珠单抗治疗有反应者。与治疗反应抵消（滞后现象）相比，治疗反应出现时不同的哮喘症状表现出不同程度的相关性，表明IgE水平和肺功能的变化有生理时间延迟。
结论：奥马珠单抗和游离IgE水平与临床症状极为相关。不建议使用低于标准剂量低的奥马珠单抗，因为随之产生的游离IgE水平升高会引起哮喘控制情况恶化。
（陈欣 审校）
J Allergy Clin Immunol. 2009 Jan;123(1):107-113
Slavin RG, et al. J Allergy Clin Immunol. 2009 Jan;123(1):107-113.e3. Links
Asthma symptom re-emergence after omalizumab withdrawal correlates well with increasing IgE and decreasing pharmacokinetic concentrations.
BACKGROUND: Physicians have questioned whether omalizumab can be discontinued or the dose reduced after clinical improvement is seen in patients with severe asthma. OBJECTIVES: To examine the relationships among omalizumab, free IgE, and clinical outcomes in a randomized, placebo-controlled trial in patients with severe persistent allergic asthma following a posology based on pretreatment total IgE and body weight.
METHODS: A pharmacokinetic-pharmacodynamic binding model was used to calculate free IgE, omalizumab, and total IgE concentrations during the 28-week treatment and 16-week follow-up of the INvestigation of Omalizumab in seVere Asthma TrEatment (INNOVATE) study. These were plotted against the mean changes in the total asthma symptom score, morning peak expiratory flow, and rescue medication use for physician-defined treatment responders and nonresponders.
RESULTS: The model accurately fitted omalizumab and free and total IgE, allowing reconstruction of the entire time course for each patient. Free IgE was rapidly suppressed below the 50 ng/mL (20.8 IU/mL) target, although there was a notable period before clinical measures stabilized. After treatment cessation, free IgE and omalizumab returned toward baseline and, after a delay, asthma symptoms re-emerged. Model-derived omalizumab and free IgE concentrations correlated well with changes in clinical outcomes, particularly in omalizumab-treated responders. Asthma symptoms exhibited different correlations during response onset compared with response offset (hysteresis), indicative of physiological time delays between changes in IgE levels and pulmonary function.
CONCLUSION: Omalizumab and free IgE correlated well with clinical symptoms. Reducing omalizumab doses below those in the dosing table cannot be recommended; the resulting increase in free IgE would cause a deterioration in asthma control.
目的：在重症、持续、过敏性哮喘患者中进行随机、安慰剂对照试验，检测奥马珠单抗、游离IgE和临床结局间的关系，随后根据试验前的总IgE水平和体重进行剂量学研究。
方法：采用药代动力学—药效学结合模型计算奥马珠单抗在重症哮喘治疗中的作用研究(INNOVATE)中28周治疗期间和16周随访期间游离IgE、奥马珠单抗和总IgE水平。绘图表示与哮喘症状总分、晨间呼气流量峰值和对医生确定的对治疗有反应者和无反应者的补救性用药的平均改变间的关系。
结果：该模型将奥马珠单抗与游离IgE和总IgE水平准确的结合，使得每个患者完整的时程都得以重建。游离IgE水平被迅速抑制，低于50 ng/mL（20.8 IU/mL），尽管在临床检测稳定前有较长一段时间。治疗停止后，奥马珠单抗和游离IgE水平回复到基线水平，经过一段延迟，哮喘症状再次出现。从模型得到的奥马珠单抗和游离IgE水平与临床结局的改变极为相关，特别是对奥马珠单抗治疗有反应者。与治疗反应抵消（滞后现象）相比，治疗反应出现时不同的哮喘症状表现出不同程度的相关性，表明IgE水平和肺功能的变化有生理时间延迟。
结论：奥马珠单抗和游离IgE水平与临床症状极为相关。不建议使用低于标准剂量低的奥马珠单抗，因为随之产生的游离IgE水平升高会引起哮喘控制情况恶化。
（陈欣 审校）
J Allergy Clin Immunol. 2009 Jan;123(1):107-113
Slavin RG, et al. J Allergy Clin Immunol. 2009 Jan;123(1):107-113.e3. Links
Asthma symptom re-emergence after omalizumab withdrawal correlates well with increasing IgE and decreasing pharmacokinetic concentrations.
BACKGROUND: Physicians have questioned whether omalizumab can be discontinued or the dose reduced after clinical improvement is seen in patients with severe asthma. OBJECTIVES: To examine the relationships among omalizumab, free IgE, and clinical outcomes in a randomized, placebo-controlled trial in patients with severe persistent allergic asthma following a posology based on pretreatment total IgE and body weight.
METHODS: A pharmacokinetic-pharmacodynamic binding model was used to calculate free IgE, omalizumab, and total IgE concentrations during the 28-week treatment and 16-week follow-up of the INvestigation of Omalizumab in seVere Asthma TrEatment (INNOVATE) study. These were plotted against the mean changes in the total asthma symptom score, morning peak expiratory flow, and rescue medication use for physician-defined treatment responders and nonresponders.
RESULTS: The model accurately fitted omalizumab and free and total IgE, allowing reconstruction of the entire time course for each patient. Free IgE was rapidly suppressed below the 50 ng/mL (20.8 IU/mL) target, although there was a notable period before clinical measures stabilized. After treatment cessation, free IgE and omalizumab returned toward baseline and, after a delay, asthma symptoms re-emerged. Model-derived omalizumab and free IgE concentrations correlated well with changes in clinical outcomes, particularly in omalizumab-treated responders. Asthma symptoms exhibited different correlations during response onset compared with response offset (hysteresis), indicative of physiological time delays between changes in IgE levels and pulmonary function.
CONCLUSION: Omalizumab and free IgE correlated well with clinical symptoms. Reducing omalizumab doses below those in the dosing table cannot be recommended; the resulting increase in free IgE would cause a deterioration in asthma control.
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吸入性皮质类固醇类药物治疗哮喘：这些药物一样吗？
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哮喘治疗中选择性PDE4抑制剂的随机、安慰剂对照研究
