08.46 Alterations in peripheral blood b-cell subsets following conventional and tnf-inhibitor therapies in patients with early, treatment-naïve rheumatoid arthritis

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Abstract

Background

In rheumatoid arthritis (RA), several studies demonstrate functionally distinct peripheral B-cell subsets relate to disease duration and response to B-cell depleting rituximab therapy.1–3 Changes following treatment with tumour necrosis factor (TNF)-inhibitor (TNFi) in peripheral blood and tonsillar tissue as well as synovial tissue have been reported.4,5 We have previously noted decreased peripheral memory B-cell and increased plasmablast numbers in active RA on no disease modifying anti-rheumatic drug (DMARD) compared with healthy controls (unpublished observations). Whilst methotrexate (MTX)-induced remission was associated with lower plasmablasts, TNFi (adalimumab+etanercept)-induced remission led to high peripheral plasmablasts.

Background

The aim of this study was to investigate further changes in peripheral B-cell subset populations with first-line conventional and TNF-inhibitor-induced suppression of inflammation.

Materials and methods

Highly sensitive flow cytometry was performed on peripheral blood of 120 patients with early, treatment-naïve RA, randomised to either etanercept/MTX or MTX +/- additional conventional DMARD, switching to etanercept/MTX at 6 months if remission was not achieved.6 Preliminary baseline-week 24 findings are reported.

Results

Baseline: No significant differences in absolute number of or percentage B-cell populations were observed between groups 1 and 2.

Results

Week 0–24 changes: ETN/MTX: Total number of B-cells increased from week 0–24, (0.1083–0.1557); specifically, significant memory cell (0.0226–0.0338, p<0.05) increase with non-significant naïve cell increase and plasmablast number decrease (0.0026–0.0021). These changes reflected significant decrease in percentage plasmablast (2.4%–1.48%); with non-significant increase in percentage memory and naïve cell.

Results

MTX/conventional DMARD: All changes following treatment were non-significant. Numerical increase in absolute naïve (0.0952–0.0964) and memory B-cells (0.0272–0.0321); with decrease in plasmablast (0.0027–0.0012) numbers was observed. However, non-significant percentage naïve population decrease (76.88–73.78) and plasmablast (2.29–1.50); with percentage increase in memory cells (20.78–24.73) was observed.

Conclusions

Initial analysis demonstrates more marked alteration in B-cell population composition following first-line ETN/MTX compared to conventional DMARD alone, with absolute increase in memory but percentage decrease in plasmablast cells. This suggests more efficient B-cell homeostasis with ETN/MTX combination in early RA (compared to established). More effective (synovial) inflammation suppression, additional role of MTX +/- etanercept also targeting lymphotoxin may underlie these observations. Planned detailed analysis will clarify the relationships further, including disease activity state and response status.

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