Propranolol vs Prednisolone for Symptomatic Proliferating Infantile Hemangiomas: A Randomized Clinical Trial | Dermatology | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
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Original Investigation
April 2014

Propranolol vs Prednisolone for Symptomatic Proliferating Infantile Hemangiomas: A Randomized Clinical Trial

Author Affiliations
  • 1Department of Otolaryngology, Children’s National Medical Center, Washington, DC
  • 2Department of Biostatistics, Children’s National Medical Center, Washington, DC
  • 3Department of General Surgery, Children’s National Medical Center, Washington, DC
  • 4Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts
  • 5Department of Plastic Surgery, Children’s National Medical Center, Washington, DC
  • 6Department of Cardiology, Children’s National Medical Center, Washington, DC
  • 7Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland
JAMA Otolaryngol Head Neck Surg. 2014;140(4):323-330. doi:10.1001/jamaoto.2013.6723
Abstract

Importance  While propranolol is touted as superior to prednisolone for treating infantile hemangiomas (IH), a randomized clinical trial (RCT) comparing the outcome and tolerability of these medications for symptomatic, proliferating IH has not been reported.

Objectives  To determine if oral propranolol is more efficacious and better tolerated than prednisolone in treating symptomatic, proliferating IH and to determine the feasibility of conducting a multi-institutional, RCT comparing efficacy and tolerability of both medications.

Design, Setting, and Participants  Phase 2, investigator-blinded, multi-institutional RCT conducted in 3 academic vascular anomalies clinics on 19 of 44 eligible infants aged between 2 weeks and 6 months. All participating patients had symptomatic proliferating IH treated between September 1, 2010, and August 1, 2012.

Interventions  Treatment with oral propranolol vs prednisolone (2.0 mg/kg/d) until halted owing to toxic effects or clinical response.

Main Outcomes and Measures  Primary outcome was change in IH size after 4 months of therapy. Secondary outcomes were response rate and frequency and severity of adverse events (AEs).

Results  The primary outcome showed no difference in lesion size or affected skin area after 4 months of therapy: 41% and 1.32 mm2 for prednisolone vs 64% and 0.55 mm2 for propranolol (P = .12 for lesion size, and P = .56 for affected skin area). Longitudinal analyses showed a faster response in total lesion outer dimension with prednisolone (P = .03), but this advantage over time was not noted when central clearing and outer dimension were included in the analysis (P = .91). The overall frequency of AEs was similar (44 for prednisolone vs 32 for propranolol) (P = .84), but prednisolone-treated participants had more grade 3 severe AEs (11 vs 1) (P = .01), particularly growth retardation resulting in size and weight below the fifth percentile. Early study withdrawal owing to AEs occurred in 6 (75%) of 8 patients in the prednisolone group but 0 of 11 propranolol-treated participants. The mean duration of therapy was shorter for prednisolone (141 vs 265 days), reflecting the higher rate of early withdrawals.

Conclusions and Relevance  Both medications show similar efficacy for reducing the area of symptomatic, proliferating IH. Although prednisolone showed a faster response rate, propranolol was better tolerated with significantly fewer severe AEs. Propranolol should be the first line of therapy for symptomatic IH unless contraindicated or unless future studies demonstrate severe AEs from propranolol. Recruiting participants for a phase 3 RCT would be difficult owing to safety profiles measured here and emerging trends favoring propranolol.

Trial Registration  clinicaltrials.gov Identifier: NCT00967226

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