Sivakumar Chinnadurai1, Christopher Fonnesbeck2, Kristen M Snyder3, Nila A Sathe4, Anna Morad5, Frances E Likis6, Melissa L McPheeters4. 1. Departments of Otolaryngology, sivakumar.chinnadurai@vanderbilt.edu. 2. Biostatistics. 3. Division of Pediatric Hematology/Oncology, Helen DeVos Children's Hospital, Grand Rapids, Michigan; and Division of Pediatric Hematology/Oncology, Monroe Carell Jr Children's Hospital at Vanderbilt, Nashville, Tennessee. 4. Health Policy, and Vanderbilt Evidence-Based Practice Center, Institute for Medicine and Public Health, Vanderbilt University Medical Center, Nashville, Tennessee; 5. Pediatrics, and. 6. Vanderbilt Evidence-Based Practice Center, Institute for Medicine and Public Health, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt University School of Nursing, Nashville, Tennessee.
Abstract
CONTEXT: Infantile hemangiomas (IH) may be associated with significant functional impact. OBJECTIVE: The objective of this study was to meta-analyze studies of pharmacologic interventions for children with IH. DATA SOURCES: Data sources were Medline and other databases from 1982 to June 2015. STUDY SELECTION: Two reviewers assessed studies using predetermined inclusion criteria. DATA EXTRACTION: One reviewer extracted data with review by a second. RESULTS: We included 18 studies in a network meta-analysis assessing relative expected rates of IH clearance associated with β-blockers and steroids. Oral propranolol had the largest mean estimate of expected clearance (95%; 95% Bayesian credible interval [BCI]: 88%-99%) relative to oral corticosteroids (43%, 95% BCI: 21%-66%) and control (6%, 95% BCI: 1%-11%). Strength of evidence (SOE) was high for propranolol's effects on reducing lesion size compared with observation/placebo. Corticosteroids demonstrated moderate effectiveness at reducing size/volume (moderate SOE for improvement in IH). SOE was low for effects of topical timolol versus placebo. LIMITATIONS: Methodologic limitations of available evidence may compromise SOE. Validity of meta-analytic estimates relies on the assumption of exchangeability among studies, conditional on effects of the intervention. Results rely on assumed lack of reporting bias. CONCLUSIONS: Propranolol is effective at reducing IH size compared with placebo, observation, and other treatments including steroids in most studies. Corticosteroids demonstrate moderate effectiveness at reducing IH size/volume. The meta-analysis estimates provide a relative ranking of anticipated rates of lesion clearance among treatments. Families and clinicians making treatment decisions should also factor in elements such as lesion size, location, number, and type, and patient and family preferences.
CONTEXT: Infantile hemangiomas (IH) may be associated with significant functional impact. OBJECTIVE: The objective of this study was to meta-analyze studies of pharmacologic interventions for children with IH. DATA SOURCES: Data sources were Medline and other databases from 1982 to June 2015. STUDY SELECTION: Two reviewers assessed studies using predetermined inclusion criteria. DATA EXTRACTION: One reviewer extracted data with review by a second. RESULTS: We included 18 studies in a network meta-analysis assessing relative expected rates of IH clearance associated with β-blockers and steroids. Oral propranolol had the largest mean estimate of expected clearance (95%; 95% Bayesian credible interval [BCI]: 88%-99%) relative to oral corticosteroids (43%, 95% BCI: 21%-66%) and control (6%, 95% BCI: 1%-11%). Strength of evidence (SOE) was high for propranolol's effects on reducing lesion size compared with observation/placebo. Corticosteroids demonstrated moderate effectiveness at reducing size/volume (moderate SOE for improvement in IH). SOE was low for effects of topical timolol versus placebo. LIMITATIONS: Methodologic limitations of available evidence may compromise SOE. Validity of meta-analytic estimates relies on the assumption of exchangeability among studies, conditional on effects of the intervention. Results rely on assumed lack of reporting bias. CONCLUSIONS:Propranolol is effective at reducing IH size compared with placebo, observation, and other treatments including steroids in most studies. Corticosteroids demonstrate moderate effectiveness at reducing IH size/volume. The meta-analysis estimates provide a relative ranking of anticipated rates of lesion clearance among treatments. Families and clinicians making treatment decisions should also factor in elements such as lesion size, location, number, and type, and patient and family preferences.