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Multicenter Study
. 2020 Feb 1;156(2):186-190.
doi: 10.1001/jamadermatol.2019.3839.

Evaluating the Safety of Oral Propranolol Therapy in Patients With PHACE Syndrome

Gerilyn M Olsen  1 , Leanna M Hansen  1 , Nicole S Stefanko  1 , Erin Mathes  2 , Katherine B Puttgen  3   4 , Megha M Tollefson  5 , Christine Lauren  6 , Anthony J Mancini  7   8 , Catherine C McCuaig  9 , Ilona J Frieden  2 , Denise Adams  10 , Eulalia Baselga  11 , Sarah Chamlin  7   8 , Deepti Gupta  12 , Peter Frommelt  13 , Maria C Garzon  6 , Kimberly Horii  14 , Justyna Klajn  10 , Mohit Maheshwari  15 , Brandon Newell  14 , Henry L Nguyen  5 , Amy Nopper  14 , Julie Powell  9 , Dawn H Siegel  1 , Beth A Drolet  1   16
Affiliations
Multicenter Study

Evaluating the Safety of Oral Propranolol Therapy in Patients With PHACE Syndrome

Gerilyn M Olsen et al. JAMA Dermatol. .

Abstract

Importance: Oral propranolol is widely considered to be first-line therapy for complicated infantile hemangioma, but its use in patients with PHACE (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, eye anomalies) syndrome has been debated owing to concerns that the cardiovascular effects of the drug may increase the risk for arterial ischemic stroke.

Objective: To assess the incidence of adverse events among patients with PHACE syndrome receiving oral propranolol for infantile hemangioma.

Design, setting, and participants: This multicenter retrospective cohort study assessed the incidence of adverse events among 76 patients with PHACE syndrome receiving oral propranolol for infantile hemangioma at 11 tertiary care, academic pediatric dermatology practices. Medical records from January 1, 2010, through April 25, 2017, were reviewed.

Exposures: Patients received oral propranolol, 0.3 mg/kg/dose or more.

Main outcomes and measures: The main outcome was the rate and severity of adverse events occurring throughout the course of treatment with oral propranolol, as documented in the medical records. Adverse events were graded from 1 to 5 using a scale derived from the Common Terminology Criteria for Adverse Events and were considered to be serious if they were grade 3 or higher.

Results: A total of 76 patients (59 girls and 17 boys; median age at propranolol initiation, 56 days [range, 0-396 days]) met the inclusion criteria. There were no reports of serious adverse events (ie, stroke, transient ischemic attack, or cardiovascular events) during treatment with oral propranolol. A total of 46 nonserious adverse events were reported among 29 patients (38.2%); the most commonly reported nonserious adverse events were sleep disturbances and minor gastrointestinal tract and respiratory tract symptoms. In a comparison with 726 infants who received oral propranolol for hemangioma but did not meet criteria for PHACE syndrome, there was no significant difference in the rate of serious adverse events experienced during treatment (0 of 76 patients with PHACE syndrome and 3 of 726 patients without PHACE syndrome [0.4%]).

Conclusions and relevance: This study found that oral propranolol was used to treat infantile hemangioma in 76 patients with PHACE syndrome and that no serious adverse events were experienced. These data provide support for the safety of oral propranolol in this patient population.

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Conflict of interest statement

Conflict of Interest Disclosures: Ms Olsen reported receiving grants from the National Institutes of Health National Heart, Lung, and Blood Institute during the conduct of the study. Dr Mathes reported serving as a consultant for Pierre Fabre and Rodan and Fields, receiving personal fees from Pierre Fabre, and receiving personal fees from Rodan and Fields outside the submitted work. Dr Puttgen reported serving on the Pierre Fabre advisory board in 2017 and receiving personal fees from Pierre Fabre Dermatologie outside the submitted work. Dr Mancini reported serving as a consultant for Pierre Fabre and on the Pierre Fabre advisory board outside the submitted work. Dr McCuaig reported serving as a consultant for Pierre Fabre and on the Pierre Fabre advisory board. Dr Frieden reported serving on the Pierre Fabre advisory board and the Venthera Medical advisory board and receiving personal fees from Pfizer and Venthera Medical outside the submitted work. Dr Adams reported serving on the Venthera Medical advisory board. Dr Baselga reported serving as a consultant for Pierre Fabre and on the Pierre Fabre advisory board and Venthera Medical advisory board and receiving personal fees from Pierre Fabre Dermatology outside the submitted work. Dr Gupta reported receiving personal fees from Pierre Fabre and QLT outside the submitted work. Dr Garzon reported being an investigator on a National Institutes of Health–sponsored study: NCT02913612 Pediatric Trials Network-NIH Efficacy, Safety and Pharmacokinetics of Topical Timolol in Infants With Infantile Hemangioma (IH) (TIM01). Dr Powell reported serving as a consultant for Pierre Fabre and on the Pierre Fabre advisory board and receiving grants and personal fees from Pierre Fabre Dermatology during the conduct of the study. Dr Siegel reported receiving grants from the National Institutes of Health and personal fees from Up to Date outside the submitted work. Dr Drolet reported serving as a consultant for Pierre Fabre and on the Pierre Fabre advisory board, reported serving as a consultant for Venthera Medical and on the Venthera Medical advisory board, receiving an investigator-initiated grant from Pierre Fabre for this study, receiving personal fees from Venthera outside the submitted work, and having a patent pending for a β-blocker for hemangioma. No other disclosures were reported.

References

    1. Haggstrom AN, Garzon MC, Baselga E, et al. . Risk for PHACE syndrome in infants with large facial hemangiomas. Pediatrics. 2010;126(2):e418-e426. doi:10.1542/peds.2009-3166 - DOI - PubMed
    1. Léaute-Labrèze C, Boccara O, Degrugillier-Chopinet C, et al. . Safety of oral propranolol for the treatment of infantile hemangioma: a systematic review. Pediatrics. 2016;138(4):e20160353. doi:10.1542/peds.2016-0353 - DOI - PubMed
    1. Krowchuk DP, Frieden IJ, Mancini AJ, et al. ; Subcommittee on the Management of Infantile Hemangiomas . Clinical practice guideline for the management of infantile hemangiomas. Pediatrics. 2019;143(1):e20183475. doi:10.1542/peds.2018-3475 - DOI - PubMed
    1. Garzon MC, Epstein LG, Heyer GL, et al. . PHACE syndrome: consensus-derived diagnosis and care recommendations. J Pediatr. 2016;178:24-33.e2. doi:10.1016/j.jpeds.2016.07.054 - DOI - PMC - PubMed
    1. US Department of Health and Human Services Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs.... Published November 27, 2017. Accessed November 4, 2019.

Publication types

Supplementary concepts