Department of Otolaryngology, Children's National Medical Center, Washington, DC.
Department of Biostatistics, Children's National Medical Center, Washington, DC.
JAMA Otolaryngol Head Neck Surg. 2014 Apr;140(4):323-30. doi: 10.1001/jamaoto.2013.6723.
While propranolol is touted as superior to prednisolone for treating infantile hemangiomas (IH), a randomized clinical trial (RCT) comparing the outcome and tolerability of these medications for symptomatic, proliferating IH has not been reported.
To determine if oral propranolol is more efficacious and better tolerated than prednisolone in treating symptomatic, proliferating IH and to determine the feasibility of conducting a multi-institutional, RCT comparing efficacy and tolerability of both medications.
DESIGN, SETTING, AND PARTICIPANTS: Phase 2, investigator-blinded, multi-institutional RCT conducted in 3 academic vascular anomalies clinics on 19 of 44 eligible infants aged between 2 weeks and 6 months. All participating patients had symptomatic proliferating IH treated between September 1, 2010, and August 1, 2012.
Treatment with oral propranolol vs prednisolone (2.0 mg/kg/d) until halted owing to toxic effects or clinical response.
Primary outcome was change in IH size after 4 months of therapy. Secondary outcomes were response rate and frequency and severity of adverse events (AEs).
The primary outcome showed no difference in lesion size or affected skin area after 4 months of therapy: 41% and 1.32 mm2 for prednisolone vs 64% and 0.55 mm2 for propranolol (P = .12 for lesion size, and P = .56 for affected skin area). Longitudinal analyses showed a faster response in total lesion outer dimension with prednisolone (P = .03), but this advantage over time was not noted when central clearing and outer dimension were included in the analysis (P = .91). The overall frequency of AEs was similar (44 for prednisolone vs 32 for propranolol) (P = .84), but prednisolone-treated participants had more grade 3 severe AEs (11 vs 1) (P = .01), particularly growth retardation resulting in size and weight below the fifth percentile. Early study withdrawal owing to AEs occurred in 6 (75%) of 8 patients in the prednisolone group but 0 of 11 propranolol-treated participants. The mean duration of therapy was shorter for prednisolone (141 vs 265 days), reflecting the higher rate of early withdrawals.
Both medications show similar efficacy for reducing the area of symptomatic, proliferating IH. Although prednisolone showed a faster response rate, propranolol was better tolerated with significantly fewer severe AEs. Propranolol should be the first line of therapy for symptomatic IH unless contraindicated or unless future studies demonstrate severe AEs from propranolol. Recruiting participants for a phase 3 RCT would be difficult owing to safety profiles measured here and emerging trends favoring propranolol. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00967226.
虽然普萘洛尔被吹捧为治疗婴儿血管瘤（IH）优于泼尼松龙，但尚未报道比较这两种药物治疗有症状、增殖性 IH 的疗效和耐受性的随机临床试验（RCT）。
确定口服普萘洛尔是否比泼尼松龙更有效且更耐受，用于治疗有症状、增殖性 IH，并确定进行比较两种药物疗效和耐受性的多机构 RCT 的可行性。
设计、地点和参与者：在 3 个学术血管异常诊所进行的 2 期、研究者盲法、多机构 RCT，纳入 44 名符合条件的年龄在 2 周至 6 个月之间的婴儿中的 19 名。所有参与的患者均接受有症状、增殖性 IH 的治疗，治疗时间为 2010 年 9 月 1 日至 2012 年 8 月 1 日。
口服普萘洛尔或泼尼松龙（2.0 mg/kg/d）治疗，直至因毒性作用或临床反应而停药。
主要结局为治疗 4 个月后 IH 大小的变化。次要结局为反应率和不良事件（AE）的频率和严重程度。
主要结局显示治疗 4 个月后病变大小或受累皮肤面积无差异：泼尼松龙组为 41%和 1.32 mm2，普萘洛尔组为 64%和 0.55 mm2（病变大小 P=0.12，受累皮肤面积 P=0.56）。纵向分析显示泼尼松龙组总病变外周尺寸的反应更快（P=0.03），但当将中央清除和外周尺寸纳入分析时，这种时间上的优势并不明显（P=0.91）。AE 的总体发生率相似（泼尼松龙组 44 例，普萘洛尔组 32 例）（P=0.84），但泼尼松龙组的 3 级严重 AE 发生率更高（11 例 vs 1 例）（P=0.01），特别是生长迟缓导致身高和体重低于第 5 百分位。泼尼松龙组 8 名患者中有 6 名（75%）因 AE 提前退出研究，但普萘洛尔组无 1 例。泼尼松龙的平均治疗持续时间较短（141 天 vs 265 天），这反映了较高的早期退出率。
两种药物对减少有症状、增殖性 IH 的面积均显示出相似的疗效。虽然泼尼松龙显示出更快的反应率，但普萘洛尔的耐受性更好，严重 AE 发生率明显较低。除非有禁忌症，或者未来的研究表明普萘洛尔有严重的 AE，否则普萘洛尔应该是治疗有症状 IH 的一线药物。由于这里测量的安全性概况和支持普萘洛尔的新兴趋势，招募 III 期 RCT 参与者将很困难。
clinicaltrials.gov 标识符：NCT00967226。
