Baseline interleukin-10 levels as a predictive biomarker for achieving clinical response with abatacept in disease-modifying antirheumatic drug-naive and anticitrullinated protein antibody-positive patients with early rheumatoid arthritis.
Academic Article
Overview
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 seropositive patients with early RA from a phase 3 study. METHODS: AVERT-2 (NCT02504268) included disease-modifying antirheumatic drug-naive, anticitrullinated protein antibody-positive patients randomized to abatacept+methotrexate (MTX) or placebo+MTX for 56 weeks. Correlations were assessed between 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+MTX and 300 received placebo+MTX. Of 103 biomarkers, 47 demonstrated a significant reduction in PD changes with abatacept+MTX versus placebo+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+MTX versus placebo+MTX, consistent with a significant reduction in disease activity with abatacept+MTX (P <0.03 to P <0.0007). Higher baseline IL-10 levels were associated with lower bone erosive development with abatacept+MTX compared with placebo+MTX. CONCLUSION: Treatment with abatacept+MTX resulted in significantly greater reduction of biomarkers relevant to RA, and high baseline IL-10 levels predicted better treatment response with abatacept+MTX versus placebo+MTX across clinical outcomes. Findings suggest a well-suited mechanism of action for abatacept+MTX in patients with early RA and high baseline IL-10 levels.
