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Suhler, E.B., Thorne, J.E., Mittal, M., et al.




摘要:目的:长期使用糖皮质激素治疗葡萄膜炎与药物相关毒性和不良事件(AEs)有关。本研究探讨了皮质类固醇剂量与皮质类固醇相关AE发生率之间的关系。设计:VISUAL-1VISUAL-2安慰剂对照临床试验事后分析。研究对象:临床试验包括活动性(VISUAL -1)和非活动性(VISUAL-2)非感染性中间,后部和全葡萄膜炎。患者随机分配接受阿达木单抗或安慰剂,并接受方案确定的强制性逐步停止口服皮质类固醇。方法:每次随访时收集不良事件数据,并由研究者对皮质类固醇关系进行评估。使用纵向泊松回归模型估计时间依赖性皮质类固醇剂量,年龄,性别,既往口服皮质类固醇剂量,既往局部皮质类固醇的使用以及免疫抑制药物的应用。仅考虑随机进行安慰剂治疗的患者。主要观察指标:主要观察指标为AEs发作频率。结果:VISUAL-1泼尼松治疗期间安慰剂患者皮质类固醇相关性AEs的发生率在统计学上高于停药后(每100 454.2/100例患者.[PY]36.1,事件发生率= 12.6P <0.001)。 VISUAL-2组患者的发病率相似(317.5 / 100PY41.1 / 100PY,事件发生率= 7.7P <0.001)。基于泊松多变量纵向广义估计方程(GEE)模型,泼尼松剂量每增加10mg,则VISUAL-1VISUAL-2皮质类固醇相关AEs率分别增加1.5倍和2.6倍(P <0.001P <0.001)。这意味着与每天服用10mg的患者相比,每天服用泼尼松60 mg / d的活动性葡萄膜炎患者平均每年会有额外10.1次(95%可信区间(CI),6.3-14.5; P <0.001)的皮质类固醇相关AEs,而每天服用泼尼松35mg /天的非活动性葡萄膜炎患者每年平均会有额外23.5次(95CI7.6-52.7; P = 0.05)的皮质类固醇相关AEs。结论:来自VISUAL-1VISUAL-2的证据表明,皮质类固醇相关AEs的发生率随着皮质类固醇剂量的增加而呈系统性增加。

PURPOSE:Chronic use of corticosteroids for the treatment of uveitis has been linked with drug-associated toxicity and adverse events (AEs). This study examines the association between corticosteroid dosage and incidence rates of corticosteroid-related AEs.DESIGN:A post hoc analysis of the VISUAL-1 and VISUAL-2 placebo-controlled clinical trials.PARTICIPANTS:The clinical trials consisted of adults with active (VISUAL-1) and inactive (VISUAL-2) noninfectious intermediate, posterior, and panuveitis. Patients were randomized to receive adalimumab or placebo and underwent a protocol-defined mandatory taper to discontinue their oral corticosteroids.METHODS:Adverse event data were collected at each visit and included an assessment of the corticosteroid relationship by the investigator. A longitudinal Poisson regression model was estimated controlling for time-dependent corticosteroid dose, age, sex, prior oral corticosteroid dose, prior topical corticosteroid use, and concomitant immunosuppressive drug use. Only patients randomized to placebo were considered.MAIN OUTCOME MEASURES:The primary outcome measure was the frequency of AEs.RESULTS:The incidence rates of corticosteroid-related AEs among placebo patients during the prednisone treatment period in VISUAL-1 was statistically higher than after discontinuation (454.2 per 100 patient-years [PY] vs. 36.1 per 100 PY, incident rate ratio= 12.6, P < 0.001). Incidence rate ratios among VISUAL-2 patients were similarly high (317.5 per 100 PY vs. 41.1 per 100 PY, incident rate ratio= 7.7, P < 0.001). Based on the Poisson multivariate longitudinal Generalized Estimating Equation (GEE) model, each 10 mg increase in prednisone dose is associated with a 1.5- and 2.6-fold increase (P < 0.001 and P < 0.001) in the rate of corticosteroid-related AEs in VISUAL-1 and VISUAL-2, respectively. This implies in turn that a patient with active uveitis taking 60 mg/day of prednisone will experience, on average, an additional 10.1 (95% confidence interval (CI), 6.3-14.5; P < 0.001) corticosteroid-related AEs per year compared with a patient taking 10 mg/day, whereas a patient with inactive uveitis taking 35 mg/day of prednisone will experience, on average, an additional 23.5 (95% CI, 7.6-52.7; P= 0.05) corticosteroid-related AEs per year compared with a patient taking 10 mg/day.CONCLUSIONS:Evidence from VISUAL-1 and VISUAL-2 suggests that the incidence rates of corticosteroid-related AEs increase systematically with corticosteroid dose.


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