Background/Purpose: Biological therapies, as TNF inhibitors (TNFi) are increasing remission rates in rheumatoid arthritis (RA) patients although these are still limited. This study aims to explore whether TNFi modulate peripheral blood mononuclear cells (PBMC) after 6 months (m) of treatment and to identify a cellular profile associated with clinical remission (REM) in patients with RA.

Methods: A prospective and observational bi-center study including 78 patients with RA treated with standard doses of their first TNFi and followed-up during 6m was carried out. All included patients fulfilled the ACR/EULAR 2010 classification criteria for RA, were adults, with moderate or high disease activity (DAS28 >3.2). PBMC were analysed by flow-cytometry at the baseline and 6m. Clinical activity at baseline and after 6m was assessed by DAS28, establishing DAS28≤2.6 as the criteria for REM. Depending on data distribution, comparisons were conducted using unpaired t, Mann-Whitney U or Fisher’s exact tests. The association between REM and the percentage of change (Δ, 6m-0m) within each PBMC subset was evaluated by uni- and multi-variable logistic regression. The presence of interactions with covariates (age, sex, disease duration, RF, ACPA, smoking habit, body mass index, baseline DAS28 and concomitant methotrexate (MTX)) was tested, stratifying the results if this was significant (p< 0.05). In case of no interaction, the model was later adjusted for these covariates.

Results: After 6m of TNFi treatment, 37% patients achieved REM. Univariable analyses (odds ratio; 95% CI; p-value) were performed to investigate the association between REM and the baseline variables. A significant association was found for lower baseline DAS28 (OR: 0.28; 95% CI: 0.19-0.51; p< 0.001). Associations of REM with other baseline patients’ characteristics, such as for age (OR: 0.97; 95% CI: 0.94-1.01; p=0.1), RF positivity (OR: 2.50; 95% CI: 0.73-8.50; p=0.1) and ACPA positivity (OR: 3.91; 95% CI: 0.80-19.07; p=0.09), were found, although not significant. Therefore, further analyses were adjusted by age, RF, ACPA and baseline DAS28. In addition, a significant association were found for reducing the percentage of naïve B cells (OR: 0.85; 95% CI: 0.73-0.99; p=0.04). A significant interaction between the change in the percentage of naïve B cells and the use of concomitant MTX was identified (Wald chi-square value=4.56; p=0.03), for the outcome of achievement of REM. Therefore, further analyses about the association between the change in the percentage of naïve B cells and REM were stratified according to the use of concomitant MTX. No significant interactions with other variables were found.

A reduction in the percentage of naïve B cells after 6m of TNFi treatment was associated with achieving REM, mainly in patients who received concomitant MTX (OR: 0.58; 95% CI: 0.38-0.90; p=0.015). However, no association was found for patients who did not received concomitant MTX (OR: 0.78; 95% CI: 0.45-1.35; p=0.4).

Conclusion: A reduction of naïve B cells was associated with the achievement of REM by TNFi therapy, mainly in patients who received concomitant methotrexate. Our results suggest that naïve B cells may be useful as a marker of REM in patients with RA cotreated with TNFi and MTX.

Baseline characteristics of patients included in the study, stratified by remission at 6 months of TNFi treatment The table shows mean±SD, median (IQR) or absolute number (percentage) for all patients included (n=78). RF, rheumatoid factor; ACPA, anti-citrullinated protein antibodies; DAS28, Disease Activity Score-28; csDMARD, conventional synthetic disease-modifying anti-rheumatic drug; MTX, methotrexate; OD, other conventional synthetic disease-modifying anti-rheumatic drugs than methotrexate. The differences between groups were analysed considering p-value < 0.05 as statistically significant result.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/reduction-in-peripheral-cd19-cd27-naive-b-cells-is-associated-with-clinical-remission-in-patients-with-rheumatoid-arthritis-receiving-combined-treatment-with-methotrexate-and-tnf-inhibitors/