Supplementary Material for: Efficacy and Safety of Anti-Interleukin-5 Therapies in Chronic Rhinosinusitis with Nasal Polyps: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

<b><i>Introduction:</i></b> The efficacy and safety of benralizumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) remain unresolved, and relevant meta-analyses are lacking. Additionally, mepolizumab has been evaluated in far fewer patients, and the evidence is unclear. We conducted a meta-analysis to identify evidence gaps that will guide future investigation of therapies targeting interleukin (IL)-5 signaling (anti-IL-5Rα or anti-IL-5) for CRSwNP. <b><i>Methods:</i></b> We performed a systematic review and meta-analysis that were registered with PROSPERO (No. CRD42021276867). A comprehensive search was performed in PubMed, Embase, Web of Science, and the Cochrane Library on September 2, 2021. Only randomized controlled trials (RCTs) assessing anti-IL-5 treatments (anti-IL-5Rα or anti-IL-5) in adult patients for CRSwNP were included. <b><i>Results:</i></b> Seven RCTs with 799 patients evaluating the efficacy and safety of treatments targeting IL-5 pathway (benralizumab [anti-IL-5Rα], mepolizumab, and reslizumab [anti-IL-5]) were included. The overall pooled meta-analysis showed that anti-IL-5 treatments were associated with a significantly better nasal polyp score (weighted mean difference [WMD]: −0.71; 95% confidence interval [CI]: [−0.87, −0.55]; <i>p</i> &lt; 0.00001). Anti-IL-5 treatments were associated with a significantly better nasal congestion score (WMD: −1.73; 95% CI: [−2.29, −1.16]; <i>p</i> &lt; 0.00001). Anti-IL-5 treatments were associated with a significantly better Sino-Nasal Outcome Test (SNOT-22) score (WMD: −11.30; 95% CI: [−14.77, −7.83]; <i>p</i> &lt; 0.00001). The overall pooled meta-analysis showed that anti-IL-5 treatments were associated with a significantly better University of Pennsylvania Smell Identification Test (UPSIT) score (WMD: 2.09; 95% CI: [0.42, 3.77]; <i>p</i> = 0.01). Anti-IL-5 treatments significantly reduced the loss of smell score in the overall pooled meta-analysis (WMD: −1.38; 95% CI: [−1.97, −0.79]; <i>p</i> &lt; 0.00001). In the overall pooled meta-analysis, anti-IL-5 treatments showed no difference with the placebo in the risk of adverse events (AEs; risk ratio [RR]: 1.01; 95% CI: [−0.93, 1.09]; <i>p</i> = 0.83) and serious AEs (SAEs; RR: 0.73; 95% CI: [0.40, 1.34]; <i>p</i> = 0.32). <b><i>Conclusion:</i></b> This systematic review and meta-analysis identified that anti-IL-5 treatments significantly improved the size of nasal polyps, health-related quality of life, and sense of smell in moderate to severe CRSwNP, and they were safe and well tolerated.

<b><i>引言：</i></b> 贝那利珠单抗（benralizumab）用于伴鼻息肉的慢性鼻-鼻窦炎（chronic rhinosinusitis with nasal polyps, CRSwNP）患者的疗效与安全性尚未明确，目前尚缺乏相关荟萃分析。此外，美泊利珠单抗（mepolizumab）的相关研究纳入患者数量极少，相关证据尚不明确。本研究开展荟萃分析以明确现有证据缺口，为未来针对伴鼻息肉的慢性鼻-鼻窦炎的白细胞介素5（interleukin, IL）-5信号通路靶向疗法（抗IL-5Rα或抗IL-5疗法）的研究提供指导。
<b><i>方法：</i></b> 本研究为已注册的系统评价与荟萃分析，已在PROSPERO平台注册（注册号：CRD42021276867）。本研究于2021年9月2日在PubMed、Embase、Web of Science及考克兰文库（Cochrane Library）中开展全面文献检索。仅纳入针对成人伴鼻息肉的慢性鼻-鼻窦炎患者、评估抗IL-5疗法（抗IL-5Rα或抗IL-5）的随机对照试验（randomized controlled trials, RCT）。
<b><i>结果：</i></b> 最终纳入7项随机对照试验，共799例患者，评估IL-5通路靶向疗法（贝那利珠单抗[抗IL-5Rα]、美泊利珠单抗及瑞利珠单抗[reslizumab，抗IL-5]）的疗效与安全性。整体合并荟萃分析结果显示，抗IL-5疗法可显著改善鼻息肉评分（加权均数差[weighted mean difference, WMD]：-0.71；95%置信区间[confidence interval, CI]：[-0.87, -0.55]；<i>p</i> &lt; 0.00001）。抗IL-5疗法可显著改善鼻塞评分（WMD：-1.73；95% CI：[-2.29, -1.16]；<i>p</i> &lt; 0.00001）。抗IL-5疗法可显著改善鼻-鼻窦结局测试22项（Sino-Nasal Outcome Test, SNOT-22）评分（WMD：-11.30；95% CI：[-14.77, -7.83]；<i>p</i> &lt; 0.00001）。整体合并荟萃分析结果显示，抗IL-5疗法可显著提升宾夕法尼亚大学嗅觉识别测试（University of Pennsylvania Smell Identification Test, UPSIT）评分（WMD：2.09；95% CI：[0.42, 3.77]；<i>p</i> = 0.01）。抗IL-5疗法可显著降低嗅觉减退评分（WMD：-1.38；95% CI：[-1.97, -0.79]；<i>p</i> &lt; 0.00001）。整体合并荟萃分析结果显示，抗IL-5疗法与安慰剂在不良事件（adverse events, AEs）发生风险（风险比[risk ratio, RR]：1.01；95% CI：[-0.93, 1.09]；<i>p</i> = 0.83）及严重不良事件（serious AEs, SAEs）发生风险（RR：0.73；95% CI：[0.40, 1.34]；<i>p</i> = 0.32）方面均无显著差异。
<b><i>结论：</i></b> 本项系统评价与荟萃分析结果显示，抗IL-5疗法可显著改善中重度伴鼻息肉的慢性鼻-鼻窦炎患者的鼻息肉体积、健康相关生存质量及嗅觉功能，且安全性良好、耐受性佳。