Serum biomarkers identified as potential predictors of baricitinib response in juvenile idiopathic arthritis

Serum biomarkers have long been investigated for their potential to aid diagnosis, prognosis, disease monitoring, and treatment response in JIA. Despite decades of research, however, clinically actionable biomarkers that can reliably guide diagnosis or therapeutic decision-making have yet to enter routine practice. In an ideal clinical setting, such biomarkers would help clinicians predict which treatment is most likely to be effective for an individual child, reducing trial-and-error prescribing and improving outcomes. 

As of 2025, the diagnosis of JIA remains primarily clinical, based on a synthesis of presenting symptoms, imaging findings, and supportive laboratory tests such as rheumatoid factor and antinuclear antibodies. The substantial heterogeneity across the seven recognized JIA subtypes has posed a major challenge to identifying a single biomarker with definitive diagnostic value. At the same time, the rapid expansion of available disease-modifying therapies and the growing emphasis on precision medicine have intensified the demand for reliable biomarkers that can inform treatment selection and strengthen clinical decision-making. 

New insights have emerged from a recent study published in The Lancet Rheumatology, which reported associations between changes in serum biomarkers and clinical response to baricitinib in patients with JIA. The findings are based on a post-hoc analysis of the phase 3 JUVE-BASIS trial, which previously demonstrated that baricitinib improved clinical outcomes in children and adolescents with multiple JIA subtypes who had an inadequate response or intolerance to conventional or biologic disease-modifying antirheumatic drugs (DMARDs). During the 12-week open-label baricitinib lead-in period, serum samples were collected and analyzed using a high-throughput proteomic platform to assess pharmacodynamic changes. 

The analysis included 168 serum samples from 84 patients, most of whom were female and White, with a mean age of 14 years. Participants were categorized as non-responders, responders, or super-responders based on clinical outcomes. After 12 weeks of treatment, significant changes were observed in multiple serum proteins, with larger and more consistent shifts seen among responders and super-responders. Notably, biomarkers associated with macrophage activation, such as CCL7, CCL18, and interleukin-6, as well as markers involved in matrix regulation, including matrix metalloproteinase-3, showed positive correlations with improvements in Juvenile Arthritis Disease Activity Score-27 (JADAS-27). 

Beyond baricitinib, a broader body of research continues to explore biomarkers as predictors of treatment response in JIA. Among the most promising candidates are myeloid-related S100 proteins, particularly MRP8/14 (S100A8/A9) and S100A12, which reflect innate immune activation. Elevated baseline levels of these proteins have been associated with better responses to methotrexate and anti–tumor necrosis factor therapies, while early declines following treatment initiation often parallel clinical improvement. In contrast, lower baseline S100 protein levels have been linked to better responses to abatacept, underscoring the treatment-specific nature of biomarker–response relationships. Traditional inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein remain useful for assessing disease activity but have limited value as standalone predictors of therapeutic response. Genetic and transcriptomic markers, including HLA-B27 status and IL1RN expression, have also shown associations with treatment outcomes in selected settings, while emerging metabolomic signatures, such as elevated hippurate levels, have been linked to methotrexate non-response, pointing to possible metabolic or microbiome influences. Cellular immune profiles and advanced imaging markers are under investigation but are not yet sufficiently validated for routine clinical use. 

The JUVE-BASIS biomarker analysis represents the first study to systematically evaluate serum protein changes in the context of a baricitinib intervention trial in the JIA population. While the findings do not yet support immediate clinical application, they offer a potential framework for identifying patients most likely to benefit from baricitinib therapy. Prospective validation in larger and more diverse cohorts will be essential before such biomarkers can be integrated into everyday clinical practice, but the study marks a meaningful step toward biomarker-guided precision medicine in JIA. 

 References 

1. Krishnan V, Keller SY, Chew C, Sims JT, Chang CY, Dow ER, Benschop RJ, Wang R, Ramanan AV. Serum biomarkers associated with baricitinib response in patients with juvenile idiopathic arthritis: a post-hoc analysis of the phase 3 JUVE-BASIS trial. Lancet Rheumatol. 2025 Nov;7(11):e799-e807. 
2. Wong SK, Twilt M. Biomarkers for juvenile idiopathic arthritis treatment response-have we identified them? Lancet Rheumatol. 2025 Nov;7(11):e752-e754.