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Resistin Associated With Juvenile Idiopathic Arthritis Response to Tofacitinib

Ekemini A. Ogbu MD, MSc, Director, Neuroinflammatory Disease Services in Rheumatology, and Codirector, Cincinnati Children's Lupus Center, Assistant Professor, UC Department of Pediatrics, and Adjunct Assistant Professor of Pediatrics, Johns Hopkins University

Ekemini A. Ogbu, MD, MSc

Credit: Linkedin

New research into biomarker associations with response to tofacitinib treatment in patients with polyarticular course juvenile idiopathic arthritis (JIA) has found that resistin was significantly associated with treatment response, although no biomarkers predicted JIA improvement after treatment initiation.1

Investigators, including lead investigator Ekemini A. Ogbu MD, MSc, Director, Neuroinflammatory Disease Services in Rheumatology, and Codirector, Cincinnati Children's Lupus Center, Assistant Professor, UC Department of Pediatrics, and Adjunct Assistant Professor of Pediatrics, Johns Hopkins University, analyzed data from 166 participants with polyarticular-course JIA from a clinical trial (NCT02592434) that received tofacitinib from baseline to week 18. Paired serum samples at baseline and week 18 were available from 143 participants.

Ogbu and colleagues assayed serial serum samples for candidate blood-based biomarkers (CBB) S100A8/9, S100A12, IL-18, SAA, resistin, VEGF, Angiopoietin-1, Angiopoietin-2, MMP8, MMP2, TIMP1, Leptin, CXCL9, sIL2R, ICAM-1, sTNFr, IL-6, IL-23, MCP1, CCL18, and CCL20. They assessed associations of CBB with participants' response to treatment from baseline to week 18.

Investigators observed a JIA-American College of Rheumatology 90 (JIA-ACR90) level improvement in 35% (n = 50), a JIA-ACR70 level improvement in 63% (n = 90), a JIA-ACR50 level improvement in 85% (n = 121), and a JIA-ACR30 level improvement in 96% (n = 137) at week 18. While there were numerical differences by JIA category, the investigators found that no baseline CBB independently predicted a decrease in 27-joint Juvenile Arthritis Disease Activity Score (JADAS-27) or JIA-ACR90 response by week 18.1

Ogbu and colleagues found that a decrease in resitin level from baseline to week 18 was significantly associated with a week 18 improvement in JADAS-27 and JIA-ACR90 response, after adjusting for age, sex, JIA disease duration and baseline resistin (r2, 0.79; standard error, 0.070; P <.01; OR, 1.134 [95% CI, 1.018-1.264]). HLA-B27 positivity was significantly associated with not achieving a JIA-ACR90 response at week 18 (P = .0097).1

Other recent research with JIA published in ACR Open Rheumatology found that patients with active JIA at 12 and 24 months were more likely to be older at diagnosis and were psoriatic, had enthesitis-related JIA, or were polyarticular rheumatoid factor (RF)-negative. Results also showed active disease at month 3 post diagnosis was linked to worse long-term outcomes.2

In 1151 analyzed participants, investigators found that older children (aged >5 years) exhibited a 40% to 45% higher point prevalence of active disease at month 12 when compared with younger patients. Those with active disease at month 3 were more likely to have greater disease prevalence at both 12 months (RP 1.5, 95% confidence interval [CI] 1.2 – 1.8) and 24 months (RP 1.3, 95% CI 1 – 1.6).2

Similarly, patients who were psoriatic, had enthesitis-related JIA, and were polyarticular RF-negative had a greater prevalence of active disease at both 12 and 24 months when compared with oligoarticular JIA. At the 24-month mark, patients aged ≥ 10 years were more likely to have greater disease activity.2


REFERENCES

1. Ogbu EA, Brunner HI, Eloseily E, et al. Biomarker Changes in Response to Tofacitinib Treatment in Patients with Polyarticular Course Juvenile Idiopathic Arthritis. Arthritis Care Res. Published online August 12, 2024. doi: 10.1002/acr.25417
2. Balay-Dustrude E, Weiss NS, Sutton A, Shenoi S. Predictors of Disease Activity in Patients With Juvenile Idiopathic Arthritis at 12 and 24 Months After Diagnosis. ACR Open Rheumatol. Published online June 17, 2024. doi:10.1002/acr2.11701

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