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.