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Predicting relapse in JIA patients upon anti-TNFA withdrawal

Major Category: Research and Disease Areas

Subcategory: Loss of Tolerance

By Leong Jing Yao (Team Lead), Camillus Chua, Lai Liyun, Pan Lu, Phyllis Chen, Sharifah Nur Hazirah, Yeo Joo Guan

Juvenile idiopathic arthritis (JIA), the most common cause of childhood chronic arthritis, comprises of 7 distinct subtypes classified by the number of joints involved, the presences of systemic or cutaneous involvements, HLA-B27 or autoantibody (rheumatoid factor, RF). Despite the significant therapeutic advancement made with biological Disease Modifying Anti-Rheumatic Drugs (DMARDs) such as anti-TNFA, leading to dramatic improvement in disease outcomes, JIA etiology remains largely unclear. However, in recent years, the field has witnessed not only advances in our understanding of JIA pathogenesis, but also attempts to address several clinical unmet needs.

In particular, one core issue is in relation to therapeutic management and disease resolution with anti-TNFA. Up to 50% of patients with JIA achieve clinical remission with long-term anti-TNFɑ treatment. While short-to-medium term treatment is well tolerated, long-term anti-TNFɑ therapy can elicit serious adverse effects. Drug withdrawal in patients who attain clinical remission is further complicated by the fact that 50-80% patients relapse upon therapy discontinuation. This phenomenon indicates that a substantial proportion of patients who attain clinical remission on medication, continue to experience subclinical inflammation and persistence of disease. Conversely, patients who achieve disease resolution at the clinical and subclinical levels could be spared long-term drug effects. As such, there is a clinical need to address how discontinuing anti-TNFɑ therapy can be safely implemented, and a scientific need to understand how disease persistence or resolution occurs.