Early Anti-Drug Antibodies Predict Adalimumab Response in Juvenile Idiopathic Arthritis

Abstract

Adalimumab, a TNF-alpha inhibitor, is approved to treat juvenile idiopathic arthritis (JIA), helping control disease activity and reduce flare frequency. This study aims to investigate predictors of treatment response, including anti-drug antibodies. We reviewed 65 JIA patients (mean age 10.47 ± 3.90 years; 61.5% male) receiving adalimumab for an average of 2.64 ± 0.56 years, with demographics, laboratory parameters, therapeutic regimens, and treatment outcomes recorded. Disease status was evaluated using the Wallace criteria up to 36 months post-treatment initiation, and anti-adalimumab antibody levels were measured after 6 months of treatment. Enthesitis-related arthritis was the most common subtype (64.6%). Inactive disease status was achieved by 83.1% of patients, with 59.3% experiencing relapse. Detectable anti-adalimumab antibody at six months (p = 0.023) and temporomandibular joint (TMJ) involvement (p = 0.038) identified those less likely to achieve inactive disease. An antibody level cutoff of 7.426 ng/mL best predicted response (AUC = 0.808; p = 0.008), while high anti-adalimumab antibody levels after treatment (p = 0.032) and an injection intervals over two weeks (p = 0.042) were predictors of future flares. Our results highlight that the presence of anti-adalimumab antibodies six months after treatment is a risk factor for poor response to adalimumab therapy.

Keywords: adalimumab; anti-drug antibodies; enthesitis-related arthritis; immunogenicity; juvenile idiopathic arthritis; outcome; risk factors.

Figure 1

Flow chart with overview of patients’ response to adalimumab treatment.

Figure 2

Predicted value of anti-adalimumab antibodies in treatment responses after 6 months of adalimumab treatment among JIA patients. (A) ROC curve of anti-adalimumab antibodies for JIA patients with persistent active disease following adalimumab treatment. The red line depicts a cutoff value of 7.426 ng/mL of anti-adalimumab antibody and the blue line depicts a cutoff value of 0. (B) Kaplan–Meier survival curve for persistency of active disease among JIA patients with a cutoff value of 7.426 ng/mL of anti-adalimumab antibody. The red line consisted of patients whose serum concentration of anti-adalimumab antibodies exceeded this threshold, while the blue line consisted of those below it.