High-dose etanercept helps children with juvenile idiopathic arthritis achieve remission and reduce disease activity: Study

Etanercept, a TNF inhibitor, was first approved by the US Food and Drug Administration in 1998 for rheumatoid arthritis and later for other conditions, including polyarticular JIA. Despite its broad use, the standard dosing in clinical trials has sometimes proven inadequate for achieving desired clinical responses in JIA patients. Consequently, off-label use at elevated doses occurs in real-world settings. The current study aimed to analyze data from the BeSt for Kids trial to evaluate the clinical outcomes of JIA patients who received high-dose etanercept versus those who did not escalate their dose despite eligibility.

Launched in 2008, the BeSt for Kids trial assessed treat-to-target approaches for JIA using different therapy combinations, including methotrexate with etanercept. Among 92 patients with oligoarticular JIA, RF-negative polyarticular JIA, or juvenile psoriatic arthritis, 32 patients received high-dose etanercept, defined as escalating up to 1.6 mg/kg per week, with a maximum of 50 mg per week. The comparator group included patients who did not escalate to high-dose etanercept despite meeting eligibility criteria.

• In the high-dose group, the median age was 6 years (IQR, 4-10), and 69% were girls. In the comparator group, the median age was 8 years (IQR, 6-9), with 73% being girls.

• The median follow-up was 24.6 months. The number of actively inflamed joints at inclusion was higher in the high-dose group (median, 11; IQR, 8-18) compared to the comparator group (median, 7; IQR, 5-11; P=0.022).

• Clinical Improvements: Significant clinical improvements within three months of dose escalation were observed:

• Median JADAS10 score reduced from 7.2 to 2.8 (P=0.008).

• VAS-physician score decreased from 12 to 4 (P=0.022).

• VAS-patient/parent score dropped from 38.5 to 13 (P=0.003).

• Number of active joints fell from 2 to 0.5 (P=0.12).

• VAS-pain score improved from 35.5 to 15 (P=0.030).

• Functional impairments, measured by the CHAQ score, improved gradually from 0.63 to 0.50 (P=0.047), while erythrocyte sedimentation rates remained stable (6 to 6; P=0.32).

• No severe adverse events were reported post-escalation. Non-severe adverse events were recorded in 81% of the high-dose group and 55% of the comparator group.

The analysis suggests that high-dose etanercept can lead to meaningful clinical improvements in children with JIA, as evidenced by significant reductions in disease activity scores and improvements in physician and patient/parent assessments. However, similar improvements were observed in the comparator group, highlighting the need for further research to establish the definitive benefits and safety of high-dose etanercept.

Researchers have found that escalating to high-dose etanercept in JIA patients can result in significant clinical improvement, although similar outcomes were observed in those who did not escalate. The study underscores the necessity for additional research to fully understand the efficacy and safety of high-dose etanercept in this patient population.

Reference:

van Dijk BT, Bergstra SA, van den Berg JM, et al. Increasing the etanercept dose in a treat-to-target approach in juvenile idiopathic arthritis: does it help to reach the target? A post-hoc analysis of the BeSt for Kids randomised clinical trial. Pediatr Rheumatol Online J. 2024;22(1):53. Published 2024 May 10. doi:10.1186/s12969-024-00989-x