AB0015 Evaluating The Effect of Anti-TNF, Anti-IL6R and Anti-CTLA4 on ACPA Isotypes in Patients with Rheumatoid Arthritis

Background B-cell depletion therapy decreases autoantibodies formation as rheumatoid factor and anti–citrullinated protein antibodies (ACPA). Other therapeutic targets (TT) such as anti-TNF (tumor necrosis factor), anti-IL-6R (interleukin-6 receptor) and anti-CTL4A (cytotoxic T-lymphocyte antigen-4) modulate the B-cells proliferation/maturation and indirectly the production of autoantibodies. ACPA titers provide us information about disease activity and may be critical for inducing clinical remission in rheumatoid arthritis (RA) patients. Objectives To evaluate the impact of the therapeutic targets: anti-TNF; anti-IL6R and anti-CTLA4 on ACPA titers in RA patients. Methods In this longitudinal study we selected ACPA positive patients naive to BT (N=27). All patients were assessed at baseline and after 4, 8, 12, 24 and 36 months (m) of treatment initiation. Disease activity was assessed by the 28 joint count-disease activity score (DAS28) according to C-Reactive Protein (CRP). ACPA isotypes (IgG, IgA and IgM) were determined by ELISA (CCP2-plates, Eurodiagnostica,SE). Anti-human antibodies isotype specific were used (Binding Site, UK). Statistical analysis was performed according to TT (anti-TNF, anti-IL6R and anti-CTLA4) and anti-TNF therapies (IFX, ADA, ETN). Results We found a significant DAS28-CRP decrease in: anti-IL6R (p=0.017, p=0.018, p=0.018, p=0.028, p=0.028) and anti-TNF (p=0.002, p=0.002, p=0.003, p=0.004, p=0.007) groups at 4, 8, 12, 24 and 36m. Evaluating the anti-TNF treatments, we found a significant decrease on DAS28 in ADL at 4 (p=0.046) and ETN groups at 4, 8, 12 and 24m of treatment (p=0.043, p=0.043, p=0.043, p=0.043). Comparing TT, the most outstanding reduction of DAS28 was found in anti-IL6R group compared to anti-CTLA4 group (p=0.017) at 8m, probably due to a greater reduction of CRP in anti-IL6R group (p=0.018). Regarding ACPA isotypes, we only found a significant decrease in IgA-ACPA titers in anti-IL6R group at 4, 8 and 12m of treatment (p=0.012, p=0.036, p=0.046). No changes were found neither in other TT nor in anti-TNF therapies. Comparing TT, we found lower IgG-ACPA titers in anti-CTLA4 group compared to anti-IL6-R group (50.25,98.2U/ml) at 4m. The highest IgG-ACPA titers were found in anti-IL6R (228.7 U/ml) than anti-TNF (53.7U/ml) and anti-CTLA4 groups (71.7U/ml) (p=0.048, p=0.024) at 24m. For IgM-ACPA, the lowest titers were found in anti-IL6R than anti-CTLA4 at 4 and 12m (4m: 2.988 y 3.093OD;12m: 3.004 y 3.116OD) (p=0.012, p=0.017, p=0.017). Conclusions Patients treated with anti-IL6R and anti-TNF had the most outstanding reduction of DAS28 at the first 8m of treatment. Regarding ACPA isotypes, IgM-ACPA levels were higher in anti-CTLA4 than anti-IL6R probably due to inhibition of B cells class-switching by anti-IL6R therapy. Those patients treated with anti-IL6R presented a progressive decrease of IgA-ACPA and total IgA, as well as, a higher IgG-ACPA titer at 24m. These results showed that both therapies modulate the B cell maturation/differentiation and ACPA production by different immune-regulation pathways, as well as, the cell-cell interaction process. Our data suggests that B-cells and ACPA isotypes monitoring may be useful to further understand their role in the RA pathogenesis and its association with clinical response to BT. Disclosure of Interest None declared