Anti-adalimumab antibodies are associated with loss of response in juvenile idiopathic arthritis

Secondary drug failure to adalimumab remains a significant challenge in managing Juvenile Idiopatihc Arthritis (JIA), with anti-adalimumab antibodies (ADA_ab) implicated as a potential mechanism. This study examines the relationship between ADA_ab formation and loss of response (LOR). In this retrospective, longitudinal study, a combination of conventional statistical methods and machine-learning algorithms were employed to investigate the association of adalimumab drug levels (ADA_drug) and ADA_ab, alongside clinical variables, on LOR among JIA patients treated between December 2016 and May 2024. LOR was defined as active disease. Among 184 patients, ADA_ab and ADA_drug emerged as the strongest predictors of LOR in random-forest analysis. In multiple logistic regression, higher ADA_ab levels were independently associated with increased risk of LOR (OR 1.18, 95% CI 1.08–1.29, p = 0.0003), while higher ADA_drug levels were associated with reduced risk (OR 0.81, 95% CI 0.68–0.95, p = 0.0103). An ADA_ab threshold of 69 AU/mL was associated with an eightfold increase in LOR (OR 8.04, 95% CI 2.8–26.1, p = 0.0002). Patients with high ADA_ab and undetectable ADA_drug had the highest risk of LOR (OR 28.24, 95% CI 7.11–111.63, p = 0.0001). Kaplan–Meier analysis demonstrated that 71% of patients with elevated ADA_ab experienced LOR within 12 months High ADA_ab levels are a significant predictor of LOR in JIA patients treated with adalimumab, particularly when coupled with low drug levels. We also report clinically meaningful one-year LOR rates. These findings support the use of therapeutic drug monitoring, which may help optimise treatment and improve long-term disease control.