Mechanism of Action of β-blockers on Infantile Hemangiomas
Although β-blockers are not (yet) US FDA-approved for the treatment of IH, there are more than 200 articles reporting their use in over 1200 patients. Many are single case reports or small series with diversified clinical settings, dosages, duration, and assessment of outcomes. To date, one randomized control trial has been published involving 40 infants with IH who received either propranolol 2 mg/kg/day divided three times daily or placebo. In the propranolol group, infants younger than 6 months and children up to 5 years of age showed reduced volume, elevation, and improved coloration in localized and segmental IH, with excellent tolerability. Two comparative effectiveness studies comparing propranolol and corticosteroids have also been published. The first study, a retrospective chart review, looked at 110 patients treated with either propranolol or corticosteroids. Propranolol was shown to be more clinically effective than oral steroids, with better tolerance and less adverse effects, and also resulted in fewer surgical interventions. In the second study, 12 IH patients treated with propranolol were retrospectively matched to those treated with prednisone based on type, location, and size of IH, as well as age at initiation of treatment. Propranolol was demonstrated to be superior when compared to prednisone at 1, 2, and months of treatment based on evaluation of serial photographs, with all patients in the propranolol group exhibiting good to excellent response.
The majority of these articles were included in two systematic reviews published in late 2012. Although slightly different methodologies were used, similar conclusions were derived, therefore supporting the significant efficacy of β-blockers in the treatment of IH. The first review assessed findings from studies of IH using corticosteroids compared with propranolol. This metaanalysis found a pooled response rate in the corticosteroid studies of 69% versus 97% for propranolol (p<0.001). The second review included all case series with a minimum of 10 patients treated with propranolol. Forty-one studies were included with a total of 1264 patients analyzed. This investigation provided more details about the methods by which propranolol in currently used. Propranolol was started at a mean age of 6.6 months, at an average dose of 2.1 mg/kg/day, with a mean duration of treatment of 6.4 months. The calculated pooled response rate of 98% in this systematic review was essentially identical to the previous analysis.
A relatively large retrospective study (42 patients) reported on the effectiveness of propranolol in IH patients who were beyond the proliferative growth phase (e.g., patients who were >12 months of age or had documented cessation of tumor growth). Propranolol at a mean dose of 2.1 mg/kg/day was found to be effective in reducing the clinical appearance of IH in children even up to the age of 10 years – a statistically significant finding that also serves to highlight the success of delayed propranolol initiation in promoting involution. The use of propranolol did not lead to any adverse effects that necessitated discontinuation of therapy.