Rebound growth of infantile hemangiomas (IHs) may occur in up to a quarter of patients treated with oral propranolol (OP) therapy, and early discontinuation of therapy may double this risk, according to a new retrospective study. These findings are published online March 7 in Pediatrics.
Among the 980 patients whose data were available for analysis, 231 (25.3%) of 912 patients experienced rebound growth, and 15.7% of these 912 patients required modification of systemic therapy. In addition, patients who discontinued therapy at younger than 9 months were twice as likely (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3 - 4.5; P = .004) to experience rebound growth compared with those patients who discontinued therapy between 12 and 15 months of age (reference group). Similarly, patients who discontinued therapy at older than 24 months also had a higher risk for rebound growth (OR, 2.5; 95% CI, 1.5 - 4.3; P < .001) when compared with the reference group.
The study authors, led by Sonal D. Shah, MD, from the University of California, San Francisco, acknowledge that previous studies have proven that OP therapy is an effective agent for the treatment of IH, a finding corroborated in the current study with an 84% mean improvement noted after more than 18 months of treatment. What remains unclear, however, are issues regarding "optimal dosing, duration of therapy, and methods for discontinuation."
Dr Shah and colleagues performed multivariate analysis to evaluate predictive factors for the development of rebound growth and found that patients with deep hemangiomas were 3.3 times more likely to experience rebound growth (OR, 3.3; 95% CI, 1.9 - 6.0; P < .001) when compared with those with superficial hemangiomas. Similar to previous findings, the researchers also found that female sex was associated with a greater risk for rebound (OR, 1.7; 95% CI, 1.1 - 2.6; P = .03). Despite not achieving significance in the multivariate analysis, the authors also note that tapering propranolol therapy vs abrupt discontinuation also resulted in a lower incidence of rebound growth (P = .01).
"The information obtained from this study underscores the need to individualize treatment depending on indications for treatment, response to treatment, and risk factors for rebound growth," write Dr Shah and colleagues.
Patients retrospectively enrolled in the study were diagnosed with IH and treated with OP between 2008 and 2013. The mean age at initiation of OP therapy was 5.6 months (standard deviation [SD], 6.8 months), and the mean total duration of therapy was 12.0 months (SD, 5.6 months). The incidence of rebound growth, its specific characteristics, and any alterations in therapy were recorded while overall response to propranolol therapy was assessed via serial clinical images using a visual analog scale.
When stratified on the basis of age at initiation of treatment, the authors found that patients who started treatment at younger than 6 months of age scored at least 6 percentage points higher on the visual analog scale than those who started therapy at 6 or more months of age.
In an accompanying commentary, Anthony J. Mancini, MD, from the Ann and Robert H. Lurie Children's Hospital of Chicago in Illinois, writes: "The data from Shah et al expand the published observations on rebound as a function of duration of OP therapy and age at the time of discontinuation or taper."
Although Dr Mancini acknowledges that several important questions remain and that further research in this area is required, he concludes: "In the meantime, the results of this large cohort review by Shah et al will help guide clinicians in optimizing OP therapy and minimizing rebound growth in select higher-risk lesions."
One coauthor is an investigator for Pﬁzer. Four coauthors are investigators for Pierre Fabre Dermatology (HEMANGEOL trial). Another coauthor has an investigator-initiated grant from Pierre Fabre Dermatology. Another coauthor is a consultant for Pierre Fabre Dermatology. The other authors have disclosed no relevant financial relationships. Dr Mancini is a consultant and speaker and receives grant support from Pierre Fabre Dermatology.
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