Background/Purpose: The advent of biological therapy has made a remarkable progress in the management of rheumatoid arthritis (RA). Abatacept (ABA), a non-TNF inhibitor, is a CTLA4-Ig and ameliorates synovial inflammation and bone damage in RA. Recent findings showed that anti-cyclic citrullinated peptide antibody (ACPA)-positive RA patients are good responders to ABA therapy in comparison with TNFi therapy, however the temporal impact of ABA on immune cells, particularly T and B cells, and its relationship with clinical response remain to be fully elucidated. In this study, we have sought to uncover these aspects by analyzing immunological changes in RA patients treated with ABA.

Methods: Twenty-five RA patients initiated with ABA as first biologic between May 2014 and March 2015 were prospectively studied with informed consent. Effects of ABA were evaluated sequentially from baseline to 52 weeks by the proportions and activation of lymphocyte subsets in peripheral blood and the titers of autoantibodies including rheumatoid factor (RF) and ACPA, along with the assessment of clinical activity.

Results: In the treatment of ABA, the proportion of CD4⁺CCR7⁺CD45RA^– (central memory) T cells enriching T follicular helper (Tfh) cells and CD4⁺CCR7^–CD45RA^– (effector memory) T cells significantly decreased, while that of CD4⁺CCR7⁺CD45RA⁺ (naive) T cells increased. Overall, activation of pathogenic Th subsets was remarkably suppressed by ABA therapy. Additionally, the proportion of CD4⁺CD25⁺CD127^loCCR4⁺ T cells (Treg) decreased. On the other hand, the proportion of B cell subsets, activation state of CD8⁺ T cells and titers of autoantibodies were minimally affected. Notably, a change in RF levels correlated well with that in Tfh numbers and disease activity (DAS28-CRP). By comparing patients who achieved good EULAR response (GR) with patients who didn’t achieve good EULAR response (non-GR) at 3 month after ABA therapy, higher RF titers and lower proportion of CD4⁺CXCR3⁺CCR6⁺ T cells (Th1Th17) among CD4+ T cells at baseline were significantly noted in the GR group (p=0.01, p=0.04, respectively). Generation of Th1Th17cells can be induced by myeloid cells stimulated with endogenous TLR4 ligands including various citrullinated proteins at joints. Using ROC curve, the cutoff values of RF and proportion of Th1Th17 were defined as 144IU/mL and 3.25%, respectively. A subpopulation of RA patients with RF titer≧144IU/mL or Th1Th17≦3.25% at baseline clearly achieved lower disease activity and better GR rates to ABA therapy.

Conclusion: Together, these findings suggest that clinical response to ABA therapy is prospectively predicted by RF titers and the proportion of a novel T cell subset in RA patients, thus helping to choose the optimal treatment strategy with the use of this biologic.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cxcr3ccr6cd4-t-cells-th1th17-and-rf-as-novel-predictive-markers-for-clinical-response-to-abatacept-treatment-in-patients-with-rheumatoid-arthritis-the-52-week-analysis/