Dosing Variation at Initiation of Adalimumab and Etanercept and Clinical Outcomes in Juvenile Idiopathic Arthritis: A Childhood Arthritis and Rheumatology Research Alliance Registry Study

Abstract

Objective To determine the dose–response relationship of tumor necrosis factor (TNF) inhibition in the treatment of juvenile idiopathic arthritis (JIA). Methods Participants of the Childhood Arthritis and Rheumatology Research Alliance Registry were eligible for inclusion in the analyses if they started TNF inhibition treatment for JIA. The primary treatment response was determined 3 to 7 months after the start of treatment, based on the JIA American College of Rheumatology Pediatric criteria for improvement, clinical Juvenile Arthritis Disease Activity Score, and persistence of treatment after 6 months. Subsequently, pooled logistic regression models were performed to include long‐term follow‐up data. The models were adjusted for risk factors associated with poor treatment response. Dosing was expressed by body weight, body surface area, ideal body weight, fat free mass, and lean body mass. Results Participants treated with adalimumab (n = 328) and etanercept (n = 437) were included in the analyses (median dose 0.82 mg/kg body weight [interquartile range (IQR) 0.66–1.04] and 0.83 mg/kg body weight [IQR 0.75–0.95], respectively). The majority of analyses did not show a relationship between dose and outcome. Where associations were found, results were conflicting. Alternative dosing characteristics based on ideal body weight, fat free mass, and lean body mass did not result in stronger or more consistent associations. Conclusion This study was not able to confirm our hypothesis that increased dosing of TNF inhibitors results in improved treatment outcomes. Although adjustment was performed for risk factors of impaired treatment response, residual confounding by indication likely explains the negative associations found in this study.

Defining a therapeutic range for adalimumab serum concentrations in the management of pediatric noninfectious uveitis, a step towards personalized treatment

“…In our study this dosing schedule resulted in a weight-based dosing variation median (IQR) of 0,85 (0.7 to 1.1) mg/kg body weight, with large interindividual variation of adalimumab TL even for weight corrected doses, supporting the need to include TDM to understand the correlation between dosing, systemic drug exposure, and treatment response. Although the use of body weight and BSA are relatively practical in clinical care, it is not clear what parameters of body composition correlate best with the systemic exposure and treatment response to adalimumab in children [ 32 ]. In a recent study Verstegen et al did not find meaningful differences between body weight and BSA in comparison to the alternative dosing parameters based on ideal body weight, fat free mass, and lean body weight [ 32 ].…”

“…Although the use of body weight and BSA are relatively practical in clinical care, it is not clear what parameters of body composition correlate best with the systemic exposure and treatment response to adalimumab in children [ 32 ]. In a recent study Verstegen et al did not find meaningful differences between body weight and BSA in comparison to the alternative dosing parameters based on ideal body weight, fat free mass, and lean body weight [ 32 ]. Neutralising ADA are well recognised for both infliximab and adalimumab and significantly affect drug serum concentrations and also inhibit their ability to bind with TNF-α.…”

Comparison of biologic monotherapy versus biologic and disease-modifying anti-rheumatic drug combination in the treatment of non-systemic juvenile idiopathic arthritis

“…In cases where cDMARDs are insufficient to provide remission, bDMARDs are preferred as both mono-and combination therapy. In clinical practice, TNFi such as ETA are the first-line biologics that are the most frequently used in JIA (11,12). Data of the German registry regarding ETA use in JIA revealed that ETA is safe and effective for treatment of JIA (13).…”