The study discussed here shows that propranolol is effective in the treatment of paediatric hemangiomas among children aged between one and five months. Previously, two randomised double-blind trials had been published, though with small numbers of participants and hence with low statistical power (14 (average 12 weeks5) and 40 (9 weeks up to 5 years6), respectively), reporting comparable findings compared to placebo. Despite the lack of high-level scientific evidence, treatment with propranolol had already become the therapy of first choice, including in the Netherlands.7
Before the introduction of propranolol, proliferating paediatric hemangiomas were treated with systemic corticosteroids, such as prednisolone (generic), as well as with radiotherapy. A systematic review published in the Cochrane Library in 20118 found only one randomised observer-blinded trial, with 20 patients, assessing the efficacy of corticosteroids for this indication9.
It is unclear whether there is a difference between propranolol and prednisolone as regards the risk of outgrowth or recurrence of the hemangioma. What is clear is that the side-effects profile of prednisolone for adults is more extensive and more serious than that of propranolol. On the other hand, the use of propranolol can result in life-threatening cardiac side-effects among small children,10 which means that the therapy should be provided by a paediatrician. Our French sister journal La Revue Prescrire recommends administering the first dose and any dosage increase at a hospital.10
Marketing propranolol in the form of the proprietary product Hemangiol® has resulted in a huge rise in the price of the drug, as pharmacy preparations are about 40 times as cheap. Similar consequences have previously been seen with the market introduction of Tecfidera® (Gebu 2015; 49: 20-22) to replace the magistral preparation of dimethyl fumarate.
In summary, the natural course of most hemangiomas is favourable. Propranolol is an effective drug for the treatment of the more severe (life- or function-threatening and ulcerating) paediatric hemangiomas, and its side-effects profile compares favourably with that of prednisolone. Long-term data on its efficacy and side-effects are lacking, so that no definitive opinion can be given on its place in the treatment. Nor is it clear up to what age drug treatment is still useful and how great the risk of outgrowth or recurrence of the hemangioma is. The fact that another randomised study was undertaken after the 2008 publication, into a drug whose patent has long since expired, is a result of new regulations on orphan indications.
- Léauté-Labrèze C, et al. Propranolol for severe hemangiomas of infancy, N Engl J Med 2008; 358: 2649-2651.
- Productinformatie propranolol (Hemangiol®), via: http://www.ema.europa.eu, human medicines, EPAR’s.
- Farmacotherapeutisch rapport propranolol (Hemangiol®), via: https://www.zorginstituutnederland.nl, Geneesmiddelenbeoordelingen.
- Léauté-Labrèze C, et al. A randomized, controlled trial of oral propranolol in infantile hemangioma. N Engl J Med 2015; 372: 735-746.
- Léauté-Labrèze C, et al. Double-blind randomized pilot trial evaluating the efficacy of oral propranolol on infantile haemangiomas in infants <4 months of age [correspondence]. Br J Dermatol 2013; 169: 181-183.
- Hogeling M, et al. A randomized controlled trial of propranolol for infantile hemangiomas. Pediatrics 2011; 128: e259-266.
- Hermans DJ, et al. Behandeling van infantiele hemangiomen met propranolol. Ned Tijdschr Geneeskd 2011; 155: A3482.
- Leonardi-Bee J, et al. Interventions for infantile haemangiomas (strawberry birthmarks) of the skin (review). Cochrane Database Syst Rev 2011: CD006545.
- Pope E, et al. Oral versus high-dose pulse corticosteroids for problematic infantile hemangiomas: a randomized, controlled trial. Pediatrics 2007; 119: e1239-1247.
- Anoniem. Propranolol (Hemangiol®). Rev Prescrire 2015; 35: 246-250.
- Drolet BA, et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics 2013; 131: 128-140.
*The literature refers to the Dutch text