- 學位論文
使用介白素23p19抑制劑治療斑塊型乾癬其感染副作用之統合分析
The infectious complication of IL-23p19 blockers for plaque psoriasis: A meta-analysis protocol
摘要
目的: 使用介白素23p19抑制劑在中度至重度斑塊型乾癬病患的感染副作用之統合分析。 研究方法: 藉由先定義的標準進行文獻回顧.使用介白素-23 抑制劑之雙盲、 隨機並使用安慰劑做為控制組的臨床試驗，收集並分析不良事件中的感染事件集合的數據來自於Risankizumab、Guselkumab 和 Tildrakizumab這些文獻利用數據資料計算風險比 與其95 %信賴區間和0.05 的雙尾統計。 統計分析基本上是以積極治療為原則 ，比較治療組 (IL23p19)與安慰劑組之間的感染事件並使用CMA 3.0版 的軟體 做為分析工具。 結果: 共有八篇文獻中的十個 隨機, 安慰劑控制的臨床試驗被納入這個統合分析。就不良事件的發生率 (RR:0.961, 95% CI: 0.899- 1.027, P=0.237) 和嚴重不良事件(RR: 0.782, 95% CI: 0.479-1.276, P=0.325) 而言， 介白質-23p19 抑制劑與安慰劑具有相似的安全性.但是若比較介白質-23p19 抑制劑與安慰劑之感染與主要心血管事件的不良事件, 使用介白質-23p19 抑制劑之感染的風險比是1.136 (RR: 1.136, 95% CI 0.999- 1.291, P=0.051) 。使用生物制劑 (IL23p19 inhibitors之主要心血管事件的風險比是0.890 ( RR: 0.890, 95% CI 0.181- 4.389, P=0.887) 。 分別分析個別介白素-23 抑制劑相較於安慰劑組有關之嚴重不良事件的數據發現: Guselkumab，相較其他兩組IL23抑制劑有較高的風險, (RR 1.463, 95% CI 0.599~3.074, P=0.404) ，因不良事件導致受試者退出臨床試驗相較安慰劑組的風險比例為 RR: 0.242, (RR 0,242, 95% CI 0.105~0.559, P: 0.001) ，使用IL23抑制劑雖然有較高的感染風險，但相較於安慰劑組卻也有效的減少大約76%受試者因不良事件退出試驗的風險。 結論: 當比較斑塊型乾癬病患使用 IL23抑制劑與安慰劑16 週後發現 ，IL23 生物製劑可能與14%增加感染風險有關。雖然兩者的主要心血管事件的風險並無統計學上的意義，但是IL23抑制劑的長期安全仍有待評估。
並列摘要
Objective: To systematically analyze the safety of Interleukin (IL)-23p19 blockers in patient with moderate to severe plaque psoriasis. Method: The literature review was performed on the predefined criteria. The searching keywords included Guselkumab, Risankizumab, and Tildrakizumab. The Interleukin (IL)-23 blocker double blind, randomization and placebo control trials were collected and the infection events in the adverse events were identified. The pooled data were from clinical trials of Guselkumab, Risankizumab, and Tildrakizumab. The Risk Ratio with 95% confidence interval (CI) and 2-sided statistical significance level of 0.05 were calculated. The statistical analysis was basically used on intend to treat; it compared the infection events between treated group and placebo group with the software of Comprehensive Meta-analysis (CMA) version 3.0. Result: A total of 10 randomized placebo-controlled trials from 8 papers were included in this meta-analysis. The IL23p19 inhibitor had similar safety results with placebos in the incidence of adverse event (AE) (RR:0.961, 95% CI: 0.899- 1.027, P=0.237) and severe adverse event (SAE) (RR: 0.782, 95% CI: 0.479-1.276, P=0.325). But the comparison of the adverse events in infection and Major Cardio-Vascular Event (MACE) between the IL23 blockers and placebo group shows that Risk Ratio (RR) of infection is 1.136 (RR: 1.136, 95% CI 0.999- 1.291, P= 0.051) in participants treated with IL23 blockers versus the placebo group. The calculated RR of MACE among the biologics is 0.890 (RR: 0.890, 95% CI 0.181- 4.389, P=0.887) in participants treated with IL23 blockers, compared to the placebo group. Separately analyzing the data of SAE on each IL 23 blockers versus placebo groups revealed that Guselkumab, with a RR of 1.463, (RR 1.463, 95% CI 0.599~3.074, P=0.404) is the highest, compared to others. The subjects discontinuing from the studies due to adverse event had RR of 0.242, (RR 0,242, 95% CI 0.105~0.559, P: 0.001). Conclusion: While comparing IL-23 blockers and placebo within 16 weeks in plaque psoriasis participants treated with IL23 biologics, they may associate with 14% increased risk of infection. Although the RR of MACE is non-statistically significant, long-term safety remains to be determined.