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Brief Report
April 7, 2021

Efficacy and Safety of Topical Timolol for the Treatment of Infantile Hemangioma in the Early Proliferative Stage: A Randomized Clinical Trial

Author Affiliations
  • 1Dermatology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  • 2Hospital Universitario Virgen del Rocío, Seville, Spain
  • 3Department of Clinical Epidemiology, CIM-Caiber-IIb Sant Pau, Barcelona, Spain
  • 4Nowwith Dermatology Service, Hospital Sant Joan de Déu, Esplugues de Llobregat, Spain
JAMA Dermatol. 2021;157(5):583-587. doi:10.1001/jamadermatol.2021.0596
Key Points

Question  Does the use of topical timolol in the first 2 months of life prevent further infantile hemangioma (IH) growth?

Findings  In this randomized clinical trial of 69 patients younger than 60 days, there were no significant differences between use of timolol and placebo for complete or nearly complete IH resolution at 24 weeks. A significant improvement in lesion color was observed at week 4 in the timolol group, and topical timolol was well tolerated.

Meaning  Topical timolol appears well tolerated in the treatment of early proliferative IH but provides limited benefit in the resolution of lesions when given during the early proliferative stage.


Importance  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.

Objective  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.

Main Outcomes and Measures  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.

Results  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.

Conclusions and Relevance  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.

Trial Registration  EudraCT Identifier: 2013-005199-17

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