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plasmablast numbers in active RA on no disease modifying anti-rheumatic drug (DMARD) compared with healthy controls (unpublished observations).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.
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.
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.
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.
Daien CI, et al. Arthritis Research & Therapy2014, 16:R95
Vital E, et al. Arthritis Rheum2010. 62(5)
Fedele AL, et al. BMC Immunology2014, 15:28
Souto-Carneiro MM, et al. Arthritis Research & Therapy2009, 11:R84
Anolik JH, et al. J Immunol2008, 180:688-692
Dumitru RB, et al. BMC MSK2016, 17:61