Novartis Pharmaceutical Corporation, 6201 South Freeway, Fort Worth, TX, 76134-2099, USA.
Alcon Laboratories, Inc., Fort Worth, TX, USA.
J Pharmacokinet Pharmacodyn. 2018 Aug;45(4):593-605. doi: 10.1007/s10928-018-9588-7. Epub 2018 Apr 21.
Olopatadine is an antihistamine and mast cell stabilizer used for treating allergic conjunctivitis. Olopatadine 0.7% has been recently approved for daily dosing in the US, which supersedes the previously approved 0.2% strength. The objective of this analysis was to characterize patients who have better itching relief at 24 h when taking olopatadine 0.7% treatment instead of olopatadine 0.2% (in terms of proportions of responses) and relate this to the severity of baseline itching as an indirect metric of a patient's sensitivity to antihistamines. A differential odds model was developed using data from two conjunctival allergen challenge (CAC) studies to characterize individual-level and population-level response to ocular itching following olopatadine treatment and the data was analyzed retrospectively. This modeling analysis was designed to predict 24 h ocular itching scores and to quantify the differences in 24 h itching relief following treatment with olopatadine 0.2% versus 0.7% in patients with moderate-to-high baseline itching. A one-compartment kinetic-pharmacodynamic E model was used to determine the effect of olopatadine. Impact of baseline itching severity, vehicle effect and the drug effect on the overall itching scores post-treatment were explicitly incorporated in the model. The model quantified trends observed in the clinical data with regards to both mean scores and the proportions of patients responding to olopatadine treatment. The model predicts a higher proportion of patients in the olopatadine 0.7% versus 0.2% group will experience relief within 24 h. This prediction was confirmed with retrospective clinical data analysis. The number of allergy patients relieved with olopatadine 0.7% increased with higher baseline itching severity scores, when compared to olopatadine 0.2%.
奥洛他定是一种抗组胺药和肥大细胞稳定剂，用于治疗过敏性结膜炎。奥洛他定 0.7%最近已在美国获得每日剂量批准，取代了之前批准的 0.2%强度。本分析的目的是描述在使用奥洛他定 0.7%治疗时，24 小时瘙痒缓解更好的患者（以反应比例表示），并将其与基线瘙痒严重程度相关联，作为患者对抗组胺药敏感性的间接指标。使用来自两项结膜变应原挑战（CAC）研究的数据，开发了一种差异优势模型，以描述奥洛他定治疗后眼部瘙痒的个体和人群水平反应，并进行回顾性数据分析。该建模分析旨在预测 24 小时眼部瘙痒评分，并量化治疗中度至重度基线瘙痒患者时，奥洛他定 0.2%与 0.7%之间 24 小时瘙痒缓解的差异。使用单室动力学-药效学 E 模型来确定奥洛他定的作用。模型明确纳入了基线瘙痒严重程度、载体效应和药物对治疗后整体瘙痒评分的影响。该模型量化了临床数据中观察到的关于平均评分和对奥洛他定治疗有反应的患者比例的趋势。该模型预测，奥洛他定 0.7%组中更多的患者将在 24 小时内缓解瘙痒。这一预测得到了回顾性临床数据分析的证实。与奥洛他定 0.2%相比，奥洛他定 0.7%缓解的过敏患者数量随着基线瘙痒严重程度评分的升高而增加。
