Infantile Hemangiomas

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Therapy for Infantile Hemangiomas

Propanolol Blows Away Corticosteroids

Graeme M. Lipper, MD

Posted: 02/08/201

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Propranolol vs Corticosteroids for Infantile Hemangiomas: A Multicenter Retrospective Analysis

Price CJ, Lattouf C, Baum B, et al
Arch Dermatol. 2011;147:1371-1376

Study Summary

Infantile hemangiomas (IH) are proliferative vascular tumors that, despite their benign nature, may cause pain, bleeding, scarring, or functional impairment with potentially life-threatening consequences. Because most IHs involute within the first decade of life, noncritical lesions are typically followed for expected gradual regression. In contrast, lesions that obstruct vision, respiration, hearing, feeding, or defecation require prompt medical or surgical intervention. Large or multifocal lesions pose significant risks, including high-output cardiac failure and cosmetic disfigurement.^[1] In the past, such high-risk IHs were treated with systemic corticosteroids, an option that is limited by variable efficacy and common adverse effects such as cushingoid features, adrenal suppression, gastritis, hypertension, and growth impairment.

In 2008, French investigators made the serendipitous discovery that propranolol, a beta-blocker traditionally used for the treatment of hypertension, tachycardia, and congestive heart failure, can induce dramatic IH regression.^[2]Subsequent reports confirming the impressive efficacy and safety of propranolol have been met with growing optimism.^[3-5] However, one pressing question remained: How does propranolol compare with systemic corticosteroids? In a landmark multicenter study, Price and colleagues convincingly answered this question. It turns out that propranolol blows the historical gold standard out of the water.

In order to reach this conclusion, Price and colleagues retrospectively analyzed the clinical outcomes in 110 infants and children with IH (77% female; 78% located on the head and neck; mean age of treatment initiation, 4.7 years). The patients were subdivided into 2 treatment groups: those receiving propranolol (n = 68; mean treatment duration, 7.9 months; target dose, 2 mg/kg/d) and those receiving oral corticosteroids (n = 42; mean treatment duration, 5.2 months; target dose, 4 mg/kg/d). To insure comparability, investigators matched these groups for patient age and lesion size, location, and type.

Outcome measures included percentage of IH clearance (< 75% or ≥ 75%), adverse effects, percentage of patients needing subsequent surgical referral, and average treatment cost per IH. Propranolol proved superior in all of these criteria:

1. 82% of patients treated with propranolol achieved ≥ 75% clearance vs 29% of patients treated with oral corticosteroids (P < .01).
2. 1 of 68 patients treated with propanolol had transient hypoglycemia, 2 patients (3%) had nonspecific skin eruptions, all patients completed treatment, and no patients suffered serious adverse events, whereas all patients treated with oral corticosteroids had adverse effects, including cushingoid features (100%), gastroesophageal reflux (n = 4), and hypertension (n = 2). One patient had a life-threatening bleed due to IH ulceration eroding into the external carotid artery.
3. 12% of patients treated with propranolol required surgery after therapy vs 29% of patients treated with oral corticosteroids.
4. The average cost per IH treated (excluding monitoring costs and prophylaxis/treatment of adverse effects) was $205.32 for propranolol vs $416.00 for oral corticosteroids.

Viewpoint

After its recent introduction by French investigators, oral propranolol has revolutionized the management of severe infantile hemangiomas. Now, thanks to Price and colleagues' seminal study, no lingering doubt should exist that propranolol is the first-line agent for treating symptomatic or cosmetically disfiguring IH. When comparing safety and efficacy of the 2 drugs, the results are not even close.

Although "propranolol blows away corticosteroids" is the headline here, the investigators of this study also made several other important observations. For example, they found that:

1. Propranolol induced IH regression even when treatment was initiated after the first year of IH growth, confirming previous reports that the drug works to debulk more mature lesions beyond the proliferative phase.^[6]
2. Initial treatment with oral corticosteroids followed by oral propranolol showed a trend toward slightly improved efficacy over propranolol alone, although this benefit was not statistically significant.
3. IHs were less likely to relapse if propranolol therapy continued until at least 1 year of age.
4. The risk for propranolol-related side effects can be minimized with proper monitoring (eg, cardiac preclearance and checking for signs or symptoms of bradycardia, hypotension, and hypoglycemia).

Finally, Price and colleagues acknowledged that at least one more critical question remains: We still do not knowhow propranolol works to slow IH and induce regression. Does it trigger endothelial cell apoptosis, inhibit proangiogenic cytokines, or cause vasoconstriction by reducing nitric oxide levels? As researchers try to solve this complex puzzle, powerful new IH treatments will surely follow
.