短期疗效和安全性的白介素-17、白介素-12/23 和白介素-23 抑制剂布罗达单抗、司库奇尤单抗、依奇珠单抗、乌司奴单抗、古塞库单抗、替西珠单抗和瑞莎珠单抗治疗中度至重度斑块状银屑病：随机对照试验的系统评价和网络荟萃分析。 - Suppr

BACKGROUND: The role of interleukin-12 (IL-12), interleukin-23 (IL-23), and interleukin-17 (IL-17) has been recognized in psoriasis pathogenesis, and new drugs targeting this axis have already been developed which may provide a new therapeutic approach for patients with moderate to severe psoriasis. OBJECTIVE: To compare the direct and indirect evidences of the efficacy and safety of brodalumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tildrakizumab, and risankizumab in the short-term treatment of moderate to severe plaque psoriasis using network meta-analysis (NMA). METHODS: A comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for the available relevant studies. NMA was conducted by Stata 15.0 software using relative risks (RR) with 95% confidence interval to assess the clinical effectiveness and safety. Ranked the efficacy and safety for each drug accordance with the surface under the cumulative ranking curve (SUCRA). RESULTS: This meta-analysis included 28 studies. All the interventions performed better than placebo in short-term achievement. Based on the result of SUCRA, ixekizumab 80 mg every 2 weeks ranked the highest in short-term achievement of PASI 75 (SUCRA = 93.0%). Brodalumab 210 mg ranked the highest in short-term achievement of PASI 100 (SUCRA = 85.0%). Secukinumab 300 mg ranked the highest in short-term achievement of sPGA 0/1 or IGA 0/1 or PGA 0/1 (SUCRA = 98.1%). In terms of having a risk of adverse events, the rates were higher in brodalumab, secukinumab, ixekizumab, and ustekinumab 45 mg compared with placebo. Ixekizumab 80 mg every 4 weeks ranked the highest in the risk of adverse events during short-term treatment (SUCRA = 4.5%). Guselkumab 50 mg ranked the highest in the risk of serious adverse events during short-term treatment (SUCRA = 25.9%). Ixekizumab 80 mg every 4 weeks ranked the highest in the risk of discontinuations due to adverse events during short-ter treatment (SUCRA = 10.7%). CONCLUSIONS: IL-17, IL-12/23, and IL-23 inhibitors had high efficacy in the achievement of PASI 75, PASI 100, and sPGA 0/1 or IGA 0/1 or PGA 0/1 in moderate to severe plaque psoriasis after 12 or 16 weeks of treatment. IL-17 inhibitors showed superior efficacy. However, its clinical safety was poor. Risankizumab appeared to have relatively high efficacy and low risk. The clinical tolerance of other biological agents needs to be further observed.

背景：白细胞介素 12（IL-12）、白细胞介素 23（IL-23）和白细胞介素 17（IL-17）在银屑病发病机制中的作用已得到认可，针对该轴的新药已经开发出来，这可能为中重度银屑病患者提供新的治疗方法。

目的：使用网络荟萃分析（NMA）比较布罗达单抗、司库奇尤单抗、依奇珠单抗、乌司奴单抗、古塞库单抗、替利珠单抗和瑞莎珠单抗在中重度斑块型银屑病短期治疗中的直接和间接疗效和安全性证据。

方法：在 PubMed、EMBASE 和 Cochrane 对照试验中心注册库中全面检索了可用的相关研究。使用 Stata 15.0 软件进行 NMA，采用相对风险（RR）和 95%置信区间评估临床疗效和安全性。根据累积排序曲线下面积（SUCRA）对每种药物的疗效和安全性进行排名。

结果：本荟萃分析纳入了 28 项研究。所有干预措施在短期治疗中均优于安慰剂。基于 SUCRA 的结果，每 2 周给予 80mg 依奇珠单抗在短期 PASI75 缓解方面排名最高（SUCRA=93.0%）。布罗达单抗 210mg 在短期 PASI100 缓解方面排名最高（SUCRA=85.0%）。司库奇尤单抗 300mg 在短期 sPGA0/1 或 IGA0/1 或 PGA0/1 缓解方面排名最高（SUCRA=98.1%）。在发生不良反应的风险方面，布罗达单抗、司库奇尤单抗、依奇珠单抗和乌司奴单抗 45mg 组的发生率高于安慰剂组。每 4 周给予 80mg 依奇珠单抗在短期治疗期间发生不良反应的风险最高（SUCRA=4.5%）。古塞库单抗 50mg 在短期治疗期间发生严重不良反应的风险最高（SUCRA=25.9%）。每 4 周给予 80mg 依奇珠单抗在短期治疗期间因不良反应停药的风险最高（SUCRA=10.7%）。

结论：IL-17、IL-12/23 和 IL-23 抑制剂在中重度斑块型银屑病患者治疗 12 或 16 周后，在 PASI75、PASI100 和 sPGA0/1 或 IGA0/1 或 PGA0/1 的缓解方面具有较高的疗效。IL-17 抑制剂显示出更好的疗效。然而，其临床安全性较差。里莎珠单抗似乎具有较高的疗效和较低的风险。其他生物制剂的临床耐受性需要进一步观察。