Toward Personalized Withdrawal of TNF-α Inhibitors in Non-Systemic Juvenile Idiopathic Arthritis: Predictors of Biologic-Free Remission and Flare.

Background

Tumor necrosis factor-α (TNFα) inhibitors have significantly improved outcomes in children with non-systemic juvenile idiopathic arthritis (JIA), achieving long-term clinical remission for many patients. However, the optimal strategy for TNF-α inhibitor withdrawal remains unknown, whether through abrupt discontinuation, gradual dose reduction, or interval extension.

Objective

We aim to identify patient-, disease-, and treatment-related predictors of successful TNF-α inhibitor withdrawal in children with non-systemic JIA.

Methods

In this prospective, randomized, open-label, single-center study, 76 children with non-systemic JIA in stable remission for ≥24 months on etanercept or adalimumab were enrolled. At the time of TNF-α inhibitor discontinuation, all patients underwent a comprehensive evaluation, including a clinical examination, laboratory tests (serum calprotectin [S100 proteins] and high-sensitivity C-reactive protein [hsCRP]), and advanced joint imaging (musculoskeletal ultrasound and magnetic resonance imaging [MRI]) to assess subclinical disease activity. Patients were randomized (1:1:1, sealed-envelope allocation) to one of three predefined tapering strategies: (I) abrupt discontinuation; (II) extension of dosing intervals (etanercept 0.8 mg/kg every 2 weeks; adalimumab 24 mg/m2 every 4 weeks); or (III) gradual dose reduction (etanercept 0.4 mg/kg weekly; adalimumab 12 mg/m2 every 2 weeks). Follow-up visits were scheduled at 3, 6, 9, 12, and 18 months to monitor for disease relapse.

Results

Higher baseline Childhood Health Assessment Questionnaire (CHAQ) scores (≥2), elevated serum calprotectin [S100 proteins] and hsCRP levels at withdrawal, imaging evidence of subclinical synovitis, and a history of uveitis were all significantly associated with increased risk of flare. No significant associations were found for other clinical or demographic characteristics.

Conclusions

Early significant clinical response, absence of subclinical disease activity, and concomitant low-dose methotrexate therapy were key predictors of sustained drug-free remission. These findings may inform personalized strategies for biologic tapering in pediatric JIA.