FROM JAMA, PEDIATRICS, AND AHRQ
Two new studies underscore the important role of oral propranolol in the first-line treatment of infantile hemangioma (IH), as well as the need for better long-term data on the safety of the beta-blocker in very young children, according to the authors.
In the first study, an uncontrolled prospective analysis of 906 infants with IH, 84% of those who stopped propranolol did so because of “satisfactory efficacy” while only 6% discontinued because of adverse drug reactions (ADRs), reported Dr. Sorilla Prey at Bordeaux (France) University and her associates. The median dose of propranolol was 2 mg/kg per day for 198 days, with a median follow-up period of 396 days, in the study, which was published on Jan. 26, in a research letter (JAMA. 2016 Jan 26;315;413-5).
Almost 9% had ADRs; most involved respiratory infections. Serious ADRs affected 2.6% of patients; the most serious were cardiac and metabolic disorders. They included one episode of serious bradycardia, as well as one fatal episode of atrioventricular block considered probably unrelated to therapy.
In a separate meta-analysis of 18 studies published online in Pediatrics in January, treatment with propranolol cleared an average of 95% of IH cases, more than double the average clearance for corticosteroids ( Pediatrics. 2016 Jan 15. pii: peds.2015-3896 ). Harms “were relatively well tolerated in the short term,” but needed longer-term study, especially of cardiovascular and metabolic effects and effects on cognition, memory, and the central nervous system, said the authors, Dr. Sivakumar Chinnadurai of Vanderbilt University, Nashville, Tenn., and his associates.
A linked comparative effectiveness review, based on this research and published by the Agency for Healthcare Research and Qualityfound a “moderate” strength of evidence for oral propranolol over steroids, alongside “moderate” evidence linking the beta-blocker to potential harms.
In an interview, Dr. Michael Cabana , who was not involved the studies, noted that historically, lesions were considered benign, but that management “has changed tremendously in the last few years.” Systematic reviews suggest that propranolol is “extremely effective” in treating IH, said Dr. Cabana, professor of pediatrics at the University of California, San Francisco. “But every child and every IH lesion is different. Usually, for thin, superficial IH lesions in low-risk areas, topical corticosteroids can still be useful.”
Because the early growth of IH is nonlinear and occurs fastest at about 1-2 months of age, high-risk patients should be referred to a pediatric dermatologist by age 4 weeks, Dr. Cabana said. These include patients with facial or ulcerated hemangiomas, lesions that could threaten vision or the airway, those associated with other anomalies, or lesions in the perineal area or lumbosacral area, he added. Propranolol can cause sleep disruption and cold hands and feet, he noted. Cardiovascular effects are “usually minor,” while hypoglycemia is usually the most serious ADR.
The overall rate of treatment-related hypoglycemia in the JAMA study was only 0.4%, but half these patients had hypoglycemic seizures. Hypoglycemia was “aggravated by the beta-adrenergic antagonist properties of propranolol, and worsening conditions of children who also had other concomitant diseases,” Dr. Prey and her associates said. Despite monitoring, bradycardia also occurred in patients with severe comorbidities.
“Prescribers must counsel parents at each follow-up visit to discontinue propranolol during fasting and intercurrent illness, especially in the setting of restricted oral intake and respiratory symptoms,” they emphasized.
The comparative effectiveness review included 148 studies and 15 randomized controlled trials. Few studies compared lasers and beta-blockers, but lasers historically have yielded much lower success rates than have more recent studies of propranolol, the researchers noted. Pulsed dye laser was generally more effective than were other laser modalities, with moderate strength of evidence for improvement in skin pigmentation and relatively low risk of pain.
A third study also published in January reported that infantile hemangiomas have become more common in recent decades in conjunction with declines in gestational age and birth weight ( J Am Acad Dermatol. 2016 Jan;74 [1] 120-6 ).
Dr. Prey and her associates were funded by Pierre Fabre Dermatologie and the French Health Products Agency. She and one coinvestigator reported involvement in clinical trials of propranolol for infantile hemangioma. The other researchers had no disclosures. The systematic review was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services. The investigators had no disclosures.
