September 10, 2012

Pegylated Interferon Therapy May Slow Growth in Children

From Medscape Medical News

Joe Barber Jr, PhD

August 13, 2012 — Pegylated interferon alpha-2 (Peg-IFN-α2a) treatment appeared to change body weight, linear growth, and body composition in children with chronic hepatitis C virus (HCV) infection, although many of these changes returned to baseline after treatment cessation, according to the findings of a prospective study by Maureen M. Jonas, MD, from Children's Hospital Boston, Massachusetts, and colleagues, who published their findings in the August issue of Hepatology.

Despite previous findings of changes in the height and weight of children treated with IFN-α for hepatitis B or HCV, many questions remain to be answered. "In particular, the question of whether and how changes in weight represent changes in body composition has never been studied," the authors write. "In addition, the long-term effects, especially on linear growth, have not been fully elucidated."

The authors included 5- to 17-year-old children with chronic HCV infection who had not received previous treatment and assigned them to receive Peg-IFN-α2a (180 μg/1.73 m2 body surface area) plus either ribavirin (15 mg/kg/day; n = 55) or placebo (15 mg/kg/day; n = 59) for 24, 48, or 72 weeks, depending on treatment response.

Among the 106 children included in the analysis, changes in weight (changes in the weight-for-age z score [WAZ] of −0.31 ± 0.03, −0.43 ± 0.04, and −0.50 ± 0.13 after 24, 48, and 72 weeks of treatment, respectively; all P < .0001), height (changes in the height-for-age z score [HAZ] of −0.14 ± 0.02, −0.28 ± 0.02, and −0.50 ± 0.07 after 24, 48, and 72 weeks of treatment, respectively; all P < .0001), and body mass index (BMI; changes in the BMI z score [BMIZ] of −0.33 ± 0.04 [P < .0001], α0.40 ± 0.04 [P < .0001], and −0.35 ± 0.14 [P = .01] after 24, 48, and 72 weeks of treatment, respectively) were seen.

WAZ and BMIZ tended to return to baseline levels by 96 weeks after treatment discontinuation, irrespective of the duration of treatment, as the group treated for 72 weeks had changes in WAZ and BMIZ of 0.01 ± 0.14 and 0.13 ± 0.09 at 96 weeks after treatment cessation, respectively. However, HAZ remained significantly below baseline at this same time (change in HAZ, α0.41 ± 0.19; P < .03).

Changes in body fat composition were also observed after Peg-IFN-α2a (changes in the percentage body fat z score of −0.12 ± 0.05 and −0.14 ± 0.06 after 24 and 48 weeks of treatment, respectively, both P = .02; changes in the free fat mass z score [FFMZ] of −0.33 ± 0.05 and −0.37 ± 0.05 after 24 and 48 weeks of treatment, respectively; both P < .0001). Of note, these particular body composition changes were not significant for those receiving 72 weeks of treatment. In addition, these values again generally returned to baseline by 96 weeks after treatment cessation, excluding FFMZ at 96 weeks after the cessation of 24-week treatment (change in FFMZ, −0.28 ± 0.08; P = .0003).

No differences in dietary habits, physical activity, or sleeping patterns were observed among the children during the study, and no abnormalities in weight, height, BMI, or body composition were observed before the start of treatment.

Despite the findings that most changes appeared to be reversible, the authors stressed the need for additional data. "It is critical that longer term growth and metabolic data are gathered to determine the ultimate effect of this therapy, so that informed decisions can be made about optimal timing of treatment in this vulnerable population," the authors write.

This work was supported by a cooperative agreement between the National Institute of Diabetes and Digestive and Kidney Diseases and the US Food and Drug Administration and, in part, by a National Institutes of Health/National Center for Research Resources Colorado CTSI grant and the following study sites: Children’s Hospital Colorado, Aurora; Children’s Hospital Boston; University of California, San Francisco; Children’s National Medical Center, Washington, DC; Columbia University Medical Center, New York City; University of Florida, Gainesville; University of Washington, Seattle; Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia; Johns Hopkins Medical Center, Baltimore, Maryland; University of Cincinnati, Ohio; and Indiana University, Indianapolis. Additional support was provided by Hoffmann-La Roche for study medications, the data coordinating center, and central laboratory costs. The authors have disclosed no relevant financial relationships.

Hepatology. 2012;56:523-531. Abstract

Source

No comments:

Post a Comment