Efficacy of Propranolol Between 6 and 12 Months of Age in High-Risk Infantile Hemangioma

Abstract

BACKGROUND AND OBJECTIVES:There is no consensus on optimal treatment duration for propranolol in infantile hemangioma (IH). We evaluated the efficacy and safety of oral propranolol solution administered for a minimum of 6 months up to a maximum of 12 months of age in high-risk IH. METHODS:This single-arm, open-label, phase 3 study was conducted in patients aged 35 to 150 days with high-risk IH in 10 hospitals between 2015 and 2017. The study comprised a 6-month initial treatment period (ITP) plus continuation up to 12 months of age if complete success was not achieved, a follow-up, and a retreatment period. Patients received oral propranolol twice daily (3 mg/kg per day). The primary end point was the success rate at the end of the ITP. Furthermore, the persistence of IH response and efficacy of retreatment was evaluated. RESULTS:The success rate after 6 months of treatment was 47%, increasing to 76% at the end of the ITP. Of the patients who achieved success, 68% sustained success for 3 months without treatment, and 24% required retreatment. Of the 8 patients who were retreated, 7 achieved success. Adverse events, reported by 80% of patients, were mild, which were expected in this population or known propranolol side effects. CONCLUSIONS:Oral propranolol administered beyond 6 months and up to 12 months of age meaningfully increases the success rate in high-risk IH. Success was sustained in most patients up to 3 months after stopping treatment. Retreatment was efficacious, and the safety profile satisfactory.abstract

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“…Indeed, the authors concluded that the use of oral propranolol is well tolerated, effective, and safe in the treatment of IH during the postproliferative phase [4,6,7]. According to the literature, the duration of treatment with systemic propranolol ranges from 1 to 16 months [3,11,12]. In our study, the duration of oral propranolol IH treatment introduced after the proliferative phase ranged from 6 to 24 months, with 15 months as a median duration of treatment.…”

“…Although propranolol is well tolerated and is rarely associated with adverse reactions [1,3], our study, nonetheless, produced minor side effects, such as somnolence and cold hands and feet. As for criteria such as gender, location, and clinical form, numerous publications give similar reports [1,3,11,13]. Propranolol withdrawal produced no relapses.…”

“…There are several proposed hypotheses, including vasoconstriction, decreased renin production, inhibition of angiogenesis, and stimulation of apoptosis. The author concluded that increased apoptosis during the second year of life can offset cellular proliferation and may be involved in initiating the regression of hemangiomas [5,11,12].…”

Vascular anomalies associated with hepatic shunting

“…Propranolol’s mechanism of action is thought to be related to regression of hemangioma cells and peripheral vasoconstriction leading to permanent involution within a couple of months (Figure 11 ). Daily dosing on 2 mg/kg/d is commonly utilized, but up to 3 mg/kg/d has been effective in high-risk airway and facial/orbital hemangiomas[ 34 ]. Corticosteroids and weekly IV vincristine have also been studied as a treatment, but the results are inferior to propranolol[ 35 ].…”

Hemangiol in infantile haemangioma: A paediatric post‐marketing surveillance drug study

“…19 However, recent studies have suggested treatment for 6 to 12 months due to a greater IH rebound growth in shorter treatment duration. 25,26 Indeed, treatment duration is mostly dependent on clinical complete lesion regression. 27 Off-label use of Hemangiol was rare in this study.…”