Nancy Y. Olson

Adalimumab with or without Methotrexate in Juvenile Rheumatoid Arthritis

BACKGROUND Tumor necrosis factor (TNF) has a pathogenic role in juvenile rheumatoid arthritis. We evaluated the efficacy and safety of adalimumab, a fully human monoclonal anti-TNF antibody, in children with polyarticular-course juvenile rheumatoid arthritis. METHODS Patients 4 to 17 years of age with active juvenile rheumatoid arthritis who had previously received treatment with nonsteroidal antiinflammatory drugs underwent stratification according to methotrexate use and received 24 mg of adalimumab per square meter of body-surface area (maximum dose, 40 mg) subcutaneously every other week for 16 weeks. We randomly assigned patients with an American College of Rheumatology Pediatric 30% (ACR Pedi 30) response at week 16 to receive adalimumab or placebo in a double-blind fashion every other week for up to 32 weeks. RESULTS Seventy-four percent of patients not receiving methotrexate (64 of 86) and 94% of those receiving methotrexate (80 of 85) had an ACR Pedi 30 response at week 16 and were eligible for double-blind treatment. Among patients not receiving methotrexate, disease flares (the primary outcome) occurred in 43% of those receiving adalimumab and 71% of those receiving placebo (P=0.03). Among patients receiving methotrexate, flares occurred in 37% of those receiving adalimumab and 65% of those receiving placebo (P=0.02). At 48 weeks, the percentages of patients treated with methotrexate who had ACR Pedi 30, 50, 70, or 90 responses were significantly greater for those receiving adalimumab than for those receiving placebo; the differences between patients not treated with methotrexate who received adalimumab and those who received placebo were not significant. Response rates were sustained after 104 weeks of treatment. Serious adverse events possibly related to adalimumab occurred in 14 patients. CONCLUSIONS Adalimumab therapy seems to be an efficacious option for the treatment of children with juvenile rheumatoid arthritis. (ClinicalTrials.gov number, NCT00048542.)

The PedsQL™ in Pediatric Asthma: Reliability and Validity of the Pediatric Quality of Life Inventory™ Generic Core Scales and Asthma Module

The PedsQL™ is a modular instrument designed to measure health-related quality of life (HRQOL) in children and adolescents ages 2–18. The PedsQL™ 4.0 Generic Core Scales were developed to be integrated with the PedsQL™ Disease-Specific Modules. The PedsQL™ 3.0 Asthma Module was designed to measure pediatric asthma-specific HRQOL. The PedsQL™ was administered to 529 families. Internal consistency reliability was demonstrated for the PedsQL™ 4.0 Total Score (α = 0.90 child, 0.91 parent report) and Asthma Module (average α = 0.71 child, 0.86 parent report). The PedsQL™ 4.0 distinguished between healthy children and children with asthma. The validity of the PedsQL™ Asthma Module was demonstrated through intercorrelations with a previously standardized asthma disease- specific instrument. Responsiveness was demonstrated through patient change over time as a result of clinical intervention. The results demonstrate the reliability, validity, and responsiveness of the PedsQL™ required for an outcome measure in pediatric asthma clinical trials and research.

Psychosocial Adjustment and the Role of Functional Status for Children with Asthma

This study examined the psychosocial adjustment of children with asthma compared to children with diabetes, with cancer, and healthy children and the role of functional status in psychosocial adjustment. The total sample included 100 children, aged 8-16 years, (mean = 11.5 years), consisting of 48 boys and 52 girls. Children with asthma scored significantly higher on measures of affective adjustment (depression and internalizing behavior), significantly lower on self-esteem, and evidenced significantly greater functional impairment. Children with cancer missed significantly more school days. After controlling for functional status, no significant differences remained in affective adjustment but absences remained significantly higher for the children with cancer.

Prevention of nonadherence to nonsteroidal anti-inflammatory medications for newly diagnosed patients with juvenile rheumatoid arthritis.

Adherence to medications for chronic pediatric diseases decreases overtime. This randomized controlled trial evaluated a clinic-based, nurse-administered educational and behavioral intervention to prevent the anticipated drop in adherence to nonsteroidal medications among newly diagnosed patients with juvenile rheumatoid arthritis. Thirty-four participants completed the study (mean age = 8.44 years, SD = 3.96), including 19 in the experimental group and 15 in the standard-treatment (education) control group. There were significant group and Group x Time effects for adherence (assessed with an electronic monitor over a 13-month period) favoring the experimental group. In contrast, the groups did not differ significantly in disease activity or functional limitations. Factors that may have prevented detection of differences in these health parameters are dicussed.

Improving Adherence to Inhaled Corticosteroids in Children With Asthma: A Pilot of a Randomized Clinical Trial

This study examined the efficacy of an educational and behavioral intervention designed to improve adherence to inhaled corticosteroids in children with asthma. Fifteen children and their caregivers were randomly assigned to either a targeted educational and behavioral intervention (treatment group) or a broader psychoeducational condition (comparison group). Given the small sample size, data were analyzed using pooled time series analysis (PTSA), a unique statistical methodology that treats observations for each participant as a separate case and provides statistical power in small samples. Participants in the treatment group showed significant improvements in adherence (16.38%) during the intervention. Participants in both groups also made clinically meaningful improvements in pulmonary function. This study addressed various limitations of previous intervention research and demonstrated that a targeted intervention including educational and behavioral components was effective in improving adherence to inhaled corticosteroids in children with asthma. Implications for adherence interventions are discussed.