Supplementary Material for: The Efficacy and Safety of Topical β-Blockers in Treating Infantile Hemangiomas: A Meta-Analysis Including 11 Randomized Controlled Trials

Background: To evaluate the efficacy and safety of topical β-blockers in the treatment of superficial infantile hemangiomas (SIH) and mixed infantile hemangiomas (MIH), respectively, and compare the efficacy and safety of topical β-blockers with other interventions. Methods: The PRISMA guidelines were adhered to. We searched for randomized controlled trials in databases from 2010 to 2018 comparing topical β-blockers with other interventions for infantile hemangiomas. The outcomes evaluated were efficacy and adverse effects. Data analyses were performed using RevMan 5.3. Publication bias was assessed to account for bias in patient selection. Results: Eleven studies, involving 1,235 patients, were subjected to this meta-analysis. Six studies compared topical β-blockers with other interventions (propranolol, placebo, corticosteroids or pulsed dye laser) in treating SIH, and 5 studies evaluated the efficacy and safety of a topical β-blocker when it was combined with another intervention in treating MIH. A topical β-blocker was discovered to be as effective as oral propranolol in treating SIH (risk ratio, RR, 0.96, 95% confidence interval, CI, 0.91–1.02, p = 0.20, I2 = 0%), and topical β-blockers were more beneficial than placebo, corticosteroids or pulsed dye laser in treating SIH (RR 2.25, 95% CI 1.66–3.05, p < 0.00001, I2 = 0%). Topical β-blockers combined with another intervention gave rise to a better clinical response in the treatment of MIH than intervention alone (RR 1.99, 95% CI 1.10–3.60, p = 0.02, I2 = 55%) (standard mean difference 0.80, 95% CI 0.28–1.31, p = 0.002, I2 = 0%). Compared with oral propranolol, topical β-blockers were associated with fewer incidences of adverse effects (RR 0.05, 95% CI 0.01–0.39, p = 0.004, I2 = 0%). No significant difference in adverse effects was found when a topical β-blocker was combined with another intervention in treating MIH (RR 1.01, 95% CI 0.58–1.74, p = 0.98, I2 = 0%). Conclusions: This meta-analysis provided evidence that topical β-blockers may replace oral propranolol as first-line therapy for SIH and that they are of additive value in treating MIH.

背景：本研究旨在分别评估局部外用β受体阻滞剂（topical β-blockers）治疗浅表性婴儿血管瘤（superficial infantile hemangiomas, SIH）与混合性婴儿血管瘤（mixed infantile hemangiomas, MIH）的疗效与安全性，并对比局部外用β受体阻滞剂与其他干预手段的疗效及安全性。
方法：本研究遵循PRISMA指南（Preferred Reporting Items for Systematic Reviews and Meta-Analyses）进行。我们检索了2010年至2018年数据库中，对比局部外用β受体阻滞剂与其他干预手段治疗婴儿血管瘤的随机对照试验（randomized controlled trial, RCT）。本研究的评价结局为疗效与不良反应。数据分析采用RevMan 5.3软件完成。同时评估了发表偏倚以校正患者选择偏倚。
结果：本Meta分析共纳入11项研究，涉及1235例患者。其中6项研究对比了局部外用β受体阻滞剂与其他干预手段（普萘洛尔（propranolol）、安慰剂（placebo）、糖皮质激素（corticosteroids）或脉冲染料激光（pulsed dye laser））治疗浅表性婴儿血管瘤的效果，另有5项研究评估了局部外用β受体阻滞剂联合其他干预手段治疗混合性婴儿血管瘤的疗效与安全性。研究发现，局部外用β受体阻滞剂治疗浅表性婴儿血管瘤的疗效与口服普萘洛尔相当（风险比（risk ratio, RR）=0.96，95%置信区间（confidence interval, CI）=0.91~1.02，p=0.20，I²=0%）；其疗效优于安慰剂、糖皮质激素及脉冲染料激光（RR=2.25，95%CI=1.66~3.05，p<0.00001，I²=0%）。局部外用β受体阻滞剂联合其他干预手段治疗混合性婴儿血管瘤的临床应答效果优于单一干预手段（RR=1.99，95%CI=1.10~3.60，p=0.02，I²=55%），标准化均数差（standard mean difference, SMD）=0.80，95%CI=0.28~1.31，p=0.002，I²=0%）。与口服普萘洛尔相比，局部外用β受体阻滞剂的不良反应发生率更低（RR=0.05，95%CI=0.01~0.39，p=0.004，I²=0%）。而局部外用β受体阻滞剂联合其他干预手段治疗混合性婴儿血管瘤时，不良反应发生率与单一干预手段无显著差异（RR=1.01，95%CI=0.58~1.74，p=0.98，I²=0%）。
结论：本Meta分析结果证实，局部外用β受体阻滞剂可替代口服普萘洛尔作为浅表性婴儿血管瘤的一线治疗方案，且在混合性婴儿血管瘤的治疗中具有附加价值。