Dermatology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Hospital Universitario Virgen del Rocío, Seville, Spain.
JAMA Dermatol. 2021 May 1;157(5):583-587. doi: 10.1001/jamadermatol.2021.0596.
Treatment of infantile hemangioma (IH) with topical timolol in the first 2 months of life (early proliferative phase) may prevent further growth and the need for treatment with oral propranolol. To our knowledge, no studies have determined whether beginning early treatment with timolol for IH is better than in other proliferative stages.
To evaluate the efficacy and safety of timolol maleate solution, 0.5%, for the early treatment of IH in infants younger than 60 days.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized, double-blind, placebo-controlled, phase 2a pilot clinical trial included patients aged 10 to 60 days with focal or segmental hemangiomas (superficial, deep, mixed, or minimal/arrested growth). Patients were randomly assigned to treatment with topical timolol maleate solution, 0.5%, or placebo twice daily for 24 weeks. Changes in lesion size (volume, thickness) and color were evaluated from photographs taken at 2, 4, 8, 12, 24, and 36 weeks. Vital signs and adverse effects were recorded at each visit. The study was carried out from November 2015 to January 2017, and data analyses were completed in September 2019.
The primary outcome of complete or nearly complete IH resolution and the secondary outcomes of changes in lesion thickness, volume, and color were evaluated by a blinded investigator.
Of the 69 patients recruited, the mean (SD) age was 48.4 (10.6) days; 55 (80%) were female; and 51 (74%), 11 (16%), 6 (9%), and 1 (1%) had superficial, mixed, abortive, or deep IHs, respectively. The IHs were localized, segmental, or indeterminate in 60 (87%), 7 (10%), and 2 (3%) patients, respectively. The IHs were located on the head and/or neck (n = 23 [33%]) or other body sites (n = 46 [67%]). The study was completed by 26 of 33 (79%) patients receiving timolol and 31 of 36 (86%) receiving placebo. There were no significant differences between timolol and placebo for complete or nearly complete IH resolution at 24 weeks (n = 11 [42%] vs n = 11 [36%]; P = .37). The odds ratio of complete or almost complete response vs no response at week 24 was 1.33 (95% CI, 0.45-3.89). There were no between-group differences in IH size (volume, thickness). An improvement in color was observed at week 4 in the timolol group, and timolol was well tolerated with no systemic adverse effects.
In this randomized clinical trial, results demonstrated that topical timolol is well tolerated for the treatment of early proliferative IH but provides limited benefit in lesion resolution when given during the early proliferative stage.
EudraCT Identifier: 2013-005199-17.
在婴儿生命的头 2 个月（早期增殖期）使用局部马来酸噻吗洛尔治疗婴儿血管瘤（IH）可能会阻止其进一步生长并避免需要使用口服普萘洛尔进行治疗。据我们所知，尚无研究确定对于 IH，早期开始用噻吗洛尔治疗是否优于其他增殖期。
评估马来酸噻吗洛尔 0.5%溶液在小于 60 天的婴儿中早期治疗 IH 的疗效和安全性。
设计、设置和参与者：这是一项多中心、随机、双盲、安慰剂对照的 2a 期临床试验，纳入了年龄在 10 至 60 天、患有局灶性或节段性血管瘤（表浅、深部、混合或微小/静止生长）的患者。患者被随机分配接受局部马来酸噻吗洛尔 0.5%溶液或安慰剂，每日 2 次，持续 24 周。从第 2、4、8、12、24 和 36 周拍摄的照片评估病变大小（体积、厚度）和颜色的变化。每次就诊时均记录生命体征和不良反应。该研究于 2015 年 11 月至 2017 年 1 月进行，数据分析于 2019 年 9 月完成。
主要结局为 IH 完全或几乎完全消退，次要结局为病变厚度、体积和颜色的变化，均由盲法研究者进行评估。
在纳入的 69 例患者中，平均（SD）年龄为 48.4（10.6）天；55 例（80%）为女性；51 例（74%）、11 例（16%）、6 例（9%）和 1 例（1%）分别患有表浅、混合、退化或深部 IH；60 例（87%）、7 例（10%）和 2 例（3%）的 IH 分别为局限性、节段性或不确定。23 例（33%）患者的 IH 位于头颈部或其他身体部位（n=23），46 例（67%）位于其他身体部位。33 例接受噻吗洛尔治疗的患者中有 26 例（79%）和 36 例接受安慰剂治疗的患者中有 31 例（86%）完成了研究。在 24 周时，噻吗洛尔组与安慰剂组在完全或几乎完全 IH 消退方面无显著差异（n=11[42%] vs n=11[36%]；P=0.37）。24 周时完全或几乎完全反应与无反应的比值比为 1.33（95%CI，0.45-3.89）。两组 IH 大小（体积、厚度）无差异。噻吗洛尔组在第 4 周时颜色改善，噻吗洛尔耐受良好，无全身不良反应。
在这项随机临床试验中，结果表明局部噻吗洛尔治疗早期增殖性 IH 耐受良好，但在早期增殖期使用时，对病变消退的益处有限。
EudraCT 标识符：2013-005199-17。
