S100 protein levels predict abatacept response in juvenile idiopathic arthritis
Click Here to Manage Email Alerts
Key takeaways:
- Lower levels of S100A8/9 and S100A12 proteins were linked to greater improvement in polyarticular JIA with abatacept.
- The result “could be a useful component of a precision medicine approach.”
Lower levels of S100 proteins at baseline predict better treatment response with abatacept in patients with polyarticular-course juvenile idiopathic arthritis, according to data published in Arthritis Research & Therapy.
“Prior research shows that S100 proteins, specifically S100A8/9 (formerly MRP8/14 or calprotectin) and S100A12 (formerly calgranulin C or EN-RAGE), may be predictive biomarkers of treatment response in rheumatic diseases, including [polyarticular JIA (pJIA)],” Hermine I. Brunner, MD, MSc, MBA, of the department of pediatrics at Cincinnati Children’s Hospital Medical Center, and colleagues wrote.
“Serum S100A8/9 and S100A12 are alarmin proteins predominantly released at inflammatory sites by activated innate immune effectors including monocytes/macrophages and neutrophils,” they added. “These proteins reflect the degree of local inflammation (eg, synovitis) and are considered to be more specific biomarkers than other systemic inflammatory biomarkers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in rheumatoid arthritis. ... However, whether baseline levels of S100 proteins predict differential treatment response to abatacept in pJIA remains unknown.”
To examine the capacity of S100A8/9 and S100A12 to predict abatacept (Orencia, Bristol Myers Squibb) treatment response in polyarticular-course JIA, Brunner and colleagues conducted an exploratory analysis of data from an international phase 3 trial. According to the researchers, the trial assessed subcutaneous abatacept in 219 patients with active polyarticular-course JIA. The current analysis included serum samples from 158 patients (mean age, 11.37 years).
The researchers compared baseline levels of the S100 proteins with changes in American College of Rheumatology JIA criteria (JIA-ACR) at 4 months, as well as baseline disease activity, measured via Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein (JADAS27-CRP). Cut-offs for high or low biomarker levels were placed at the baseline medians, which were 3,295 ng/mL for S100A8/9 and 176 ng/mL for S100A12.
At 4 months, patients with lower baseline S100A8/9 levels were more likely to achieve 90% improvement in JIA-ACR (OR = 2.54; 95% CI, 1.25-5.18) and 100% improvement in JIA-ACR (OR = 3.72; 95% CI, 1.48-9.37), according to the researchers. These patients also demonstrated greater odds of achieving inactive disease at month 4 according to JIA-ACR (OR = 4.25; 95% CI, 2.03-8.92) and JADAS27-CRP (OR = 2.34; 95% CI, 1.02-5.39), as well as JIA-ACR at month 16 (OR = 3.01; 95% CI, 1.57-5.78).
Likewise, patients with lower baseline S100A12 levels were more likely to have 90% JIA-ACR improvement (OR = 2.52; 95% CI, 1.23-5.13), 100% improvement (OR = 3.68; 95% CI, 1.46-9.28) and JIA-ACR inactive disease (OR = 3.66; 95% CI, 1.76-7.61) at 4 months. Those ORs remained elevated at month 16, at 2.03, 2.14 and 4.22, respectively.
“Lower levels of S100 proteins at baseline are predictive of more profound and sustained improvements in patients with pJIA treated with abatacept,” Brunner and colleagues wrote. “The predictive value of S100 biomarkers for abatacept response was similar, irrespective of concurrent MTX use.
“Identifying patients with pJIA who may achieve early and greater clinical response with abatacept treatment could be a useful component of a precision medicine approach in pJIA,” they added. “Thus, levels of S100 proteins may be useful to predict pJIA courses in children for whom abatacept therapy is considered.”
Collapse
Click Here to Manage Email Alerts