Higher baseline levels of interleukin-10 (IL-10), an anti-inflammatory cytokine, may help identify patients with early rheumatoid arthritis (RA) who are more likely to respond to abatacept combined with methotrexate (MTX), according to an exploratory analysis published in Arthritis & Rheumatology. The findings suggest that IL-10 could have potential as a biomarker for predicting treatment response in patients who are disease-modifying antirheumatic drug (DMARD)-naive and positive for anti-citrullinated protein antibodies (ACPA).
The analysis used data from AVERT-2, a phase 3 clinical trial (NCT02504268), to investigate inflammatory biomarkers associated with baseline disease activity, changes following treatment and subsequent clinical outcomes. Patients received either abatacept plus MTX or placebo plus MTX for 56 weeks. The investigators evaluated the relationship between baseline biomarker levels and disease activity, pharmacodynamic changes in disease-associated biomarkers following treatment, and the ability of baseline biomarkers to predict treatment response at week 52.
The analysis included 446 patients treated with abatacept plus MTX and 300 who received placebo plus MTX. Of the 103 biomarkers evaluated, 47 showed significantly greater reductions following treatment with abatacept plus MTX than with placebo plus MTX. Among these, 18 biomarkers were correlated with baseline disease activity, highlighting their potential relevance to the inflammatory processes underlying RA.
Baseline IL-10 levels emerged as a potential predictor of treatment response. Patients with higher baseline IL-10 levels had a greater probability of achieving clinical efficacy outcomes at week 52 with abatacept plus MTX than with placebo plus MTX. The associations were statistically significant, with P values ranging from less than 0.03 to less than 0.0007. Higher baseline IL-10 levels were also associated with less development of bone erosion among patients receiving abatacept plus MTX than among those receiving placebo plus MTX, suggesting a possible relationship between this biomarker and the prevention of structural joint damage.
Additional immunological evidence from research by Nakachi and colleagues provides context for the potential role of IL-10 in RA. That study investigated IL-10-producing lymphocyte activation gene 3-positive regulatory T cells (LAG-3-positive Tregs), which were less frequent in patients with RA, particularly those with higher disease activity. Their frequency increased after six months of abatacept treatment. These cells also showed greater suppression of B-cell antibody production than CD25-positive Tregs, suggesting a role in regulating immune responses associated with RA.
IL-10 is known for its immunoregulatory properties, including its ability to limit excessive inflammatory responses. The findings from the AVERT-2 analysis, together with the observations on IL-10-producing regulatory T cells, suggest that IL-10-related immune regulation may be relevant to treatment outcomes with abatacept. However, the precise mechanisms linking baseline IL-10 levels to clinical response require further investigation.
Abatacept plus MTX was associated with greater reductions in several RA-related biomarkers than placebo plus MTX. Higher baseline IL-10 levels were associated with better clinical outcomes and less bone erosion development in patients receiving the combination therapy. Although these findings support the potential of IL-10 as a predictive biomarker in early, ACPA-positive RA, they arise from an exploratory post hoc analysis and require validation in independent patient cohorts before IL-10 can be used to guide treatment selection in clinical practice.
References
- Liu J, Li Y, Fu K, Wu C, Schafer P, Connolly SE, et al. Baseline Interleukin-10 Levels as a Predictive Biomarker for Achieving Clinical Response With Abatacept in Patients Who Were Disease-Modifying Antirheumatic Drug Naive and Anti-Citrullinated Protein Antibody Positive With Early Rheumatoid Arthritis. Arthritis Rheumatol. 2026 Sep;78(9):1826-1836.
- Nakachi S, Sumitomo S, Tsuchida Y, Tsuchiya H, Kono M, Kato R, et al. Interleukin-10-producing LAG3+ regulatory T cells are associated with disease activity and abatacept treatment in rheumatoid arthritis. Arthritis Res Ther. 2017 May 16;19(1):97.