Are T cells the missing link in pre-clinical RA? Save

T cells are known to play a key role in RA pathogenesis and the diversity of the T cell repertoire is known to be reduced in RA. 

In POS0009, Anang et al. studied T-cell receptor repertoire (TCR) in lymph node and peripheral blood of IgM-RF and/or ACPA positive at-risk individuals. Of interest, at-risk individuals presented expanded TCRβ clones in both their lymph nodes and peripheral blood, suggesting specific activated state of T cells as opposed to healthy controls and the diversity of the TCRβ repertoire seemed to reduce further towards onset of RA .

This is concordant with the data from the APPIPRA study (OP0130), Phase IIB randomised controlled trial of Abatacept, known to target T cells, in ACPA+RF+ or ACPAhi (≥3 x ULN) and RF- individuals with arthralgia. After 1 year of treatment the proportion of patients diagnosed with clinical RA was importantly reduced (6% vs. 29% in the PBO group), and the effect was maintained over time although the curves tend to converge at 2 years. The safety profile was acceptable with no new signal. It would be interesting to know in this study the number needed to treat and the number needed to harm.

It would also be interesting to know patients treated with Abatacept who did develop RA during the trial had a difference response to csDMARDs than those treated w/ PBO.