Juvenile idiopathic arthritis (JIA) patients treated with etanercept or etanercept plus methotrexate (MTX) experienced a statistically significant increase in mean height, weight, and body mass index (DMI) percentiles, according to researchers from the Cincinnati Children’s Hospital Medical Center. However, JIA patients treated with MTX alone did not display an increase in growth.
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According to first author Edward Giannini, DrPh, MSc, “studies have shown that growth retardation is associated with systemic inflammation and is a potentially permanent complication of JIA.”
The study data indicate that etanercept may be safe to use in JIA patients long term, Dr. Giannini says. “Physicians administering etanercept to growing children, and the patients and families, can be comforted that this biologic does not interfere with normal growth and development,” he notes.
JIA is one of the most common rheumatic diseases in children, causing significant pain and functional disability. Prior studies have shown that JIA patients may experience impaired physical growth and development dependent upon the severity of chronic inflammation, longer duration of disease, and greater functional joint involvement.
In the new three-year, open-label, nonrandomized registry of 594 patients with polyarticular (90% of the subjects) or systemic (10% of the subjects) JIA, participants between the ages of two and 18 were treated with 0.4 mg/kg of etanercept twice weekly or 0.8mg/kg once weekly. The growth profiles for each patient were recorded at baseline and at Years One, Two, and Three, and were compared with the U.S. Centers for Disease Control and Prevention (CDC) standardized growth charts to obtain percentiles.
The mean height in the etanercept group significantly increased by 4.8 percentile points by Year Three. For patients in the etanercept plus MTX group, a significant increase in mean height in Years One, Two, and Three was also recorded, with 2.4, 3.3, and 5.6 percentiles, respectively. In the MTX-only group, the mean height percentiles showed nonsignificant decreases from baseline at Years One, Two, and Three.
Similar patterns were observed for other measures of growth, such as weight and BMI, with etanercept alone, or in combination with MTX. Mean changes in weight percentile from baseline were observed each year. In the group receiving etanercept only, increases at Years One, Two, and Three were 7.4, 10.0, and 13.0, respectively. In the etanercept plus MTX group, the respective increases were 2.9, 6.9, and 8.4. BMI percentiles increased from 9.6 to 13.8 percentile points in the etanercept-only group and from 2.1 to 5.2 percentile points in the etanercept-plus-MTX group. At the end of the three years, the mean weight percentile values were 60.1 for MTX, 56.5 for etanercept, and 55.0 for etanercept plus MTX. The mean BMI percentile values were 65.9 for MTX, 63.5 for etanercept, and 60.1 for etanercept plus MTX. No consistent effect of disease control on height was observed for any treatment groups during the study. Normal development, as assessed by Tanner staging scores, did not appear to be adversely affected in any of the treatment groups.
Noting that their results support and extend data from other studies, the authors said a realistic treatment goal for JIA should include therapy aimed at reducing inflammation to minimize disease-related disability, including growth impairment.
Commenting on the study, coauthor Daniel J. Lovell, MD, of the Children’s Hospital Medical Center in Cincinnati says, “this study adds to an ever growing list of positive outcomes for children with JIA treated with anti-[tumor-necrosis factor] TNF therapies. Anti-TNF biologic therapies have been shown to have a profound and comprehensive effect on both physiologic and psychosocial outcomes in children with polyarticular forms of JIA.”
1. Giannini EH, Ilowite NT, Lovell DJ, et al. Effects of long-term etanercept treatment on growth in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum. 2010;62:3259-3264.
Sue Pondrom is a medical journalist based in San Diego.