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

Abstract

Objective

Predictive biomarkers for patients with early rheumatoid arthritis (RA) are needed. This exploratory post hoc analysis investigated inflammatory biomarkers associated with baseline disease activity and biomarkers predictive of treatment response in patients who were seropositive with early RA from a phase 3 study.

Methods

The AVERT-2 study (NCT02504268) included patients who were disease-modifying antirheumatic drug naive and anti–citrullinated protein antibody positive randomized to abatacept and methotrexate (MTX) or placebo and MTX for 56 weeks. Correlations were assessed among biomarkers and disease activity, pharmacodynamic (PD) changes on disease-associated biomarkers in response to treatment, and baseline biomarkers to predict treatment response at week 52.

Results

In the analysis, 446 patients received abatacept and MTX and 300 received placebo and MTX. Of 103 biomarkers, 47 demonstrated a significant reduction in PD changes with abatacept and MTX versus placebo and MTX, with 18 out of 47 biomarkers showing correlations with baseline disease activity. High baseline interleukin-10 (IL-10) levels were associated with greater probability of achieving efficacy measures by week 52 in patients receiving abatacept and MTX versus placebo and MTX, consistent with a significant reduction in disease activity with abatacept and MTX (P < 0.03 to P < 0.0007). Higher baseline IL-10 levels were associated with lower bone erosive development with abatacept and MTX compared with placebo and MTX.

Conclusion

Treatment with abatacept and MTX resulted in significantly greater reduction of biomarkers relevant to RA, and high baseline IL-10 levels predicted better treatment response with abatacept and MTX versus placebo and MTX across clinical outcomes. Findings suggest a well-suited mechanism of action for abatacept and MTX in patients with early RA and high baseline IL-10 levels.