Efficacy and Safety of Topical Timolol for the Treatment of Infantile Hemangioma in the Early Proliferative Stage

Abstract

IMPORTANCETreatment 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 MEASURESThe 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. RESULTSOf 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 RELEVANCEIn 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.

An exploration of optimal time and safety of 595‐nm pulsed dye laser for the treatment of early superficial infantile hemangioma

“…The 595‐nm PDL is the laser of choice for vascular malformations and residual capillary dilation. Due to the thermally induced lysis of collagen, it can promote the deposition of adipose tissue and correct anatomical aberrations, promote tissue remodeling, and is associated with the reduction of transforming growth factor‐B1 (TGF‐B1) 6 . Complications after PDL treatment can manifest as immediate purpura, erythema, edema, and blisters.…”

“…Comparison of the number of laser treatments for six group seriously affect the mental health and quality of life of children and their families. 6 The current methods for treating IH include oral propranolol, topical timolol, oral glucocorticoids, laser treatment, surgical treatment, injection treatment, and freezing. In systemic treatment, propranolol is the first-line drug for the treatment of complex infant hemangioma.…”

Infantile Hemangiomas: An Update on Pathogenesis and Treatment

“…On the contrary, Ying et al showed in a prospective study that topical timolol had a worse visual effect than PDL laser treatment [50]. A recent randomized clinical trial confirmed the safety of 0.5% timolol maleate solution but showed no significant differences in IH resolution in comparison to placebo when administered in the early proliferative stage [51]. Topical timolol was also reported to be effective in the treatment of an iris hemangioma [52].…”

Infantile Hemangioma: A Current Review

“…Timolol maleate is a topical formulation of nonselective beta-blockade that has proven beneficial for the management of small, superficial IH 122–126. The most common treatment regimen uses 0.5% gel forming solution, 1 drop gently rubbed into the IH twice a day 54,127.…”

“…89 Topical Beta-Blockade Timolol maleate is a topical formulation of nonselective beta-blockade that has proven beneficial for the management of small, superficial IH. [122][123][124][125][126] The most common treatment regimen uses 0.5% gel forming solution, 1 drop gently rubbed into the IH twice a day. 54,127 In a multicenter retrospective cohort study of 731 patients with IH treated with topical timolol, therapy duration and thickness ≤ 1 mm were significant predictors of positive treatment response.…”