Background/Purpose:

Rituximab (RTX) is directed against CD20 antigens in B lymphocytes (BL), producing selective depletion of BL, not affecting mature plasmatic cells, without immediate effect on immunoglobulin (Ig) levels.¹ RTX retreatment decrease serum Ig levels which could increase infection risk.² Current guidelines recommend optimization of biologic therapy once remission has achieved in rheumatoid arthritis (RA) patients. A serum biomarker able to predict what patients would maintain remission after optimization in RTX treated RA patients is lacking. In previous studies, RA patients with good response to RTX show significant decreases in DAS28 scores associated to maintained BL depletion.³

Purpose: to analyze the predictive value of CD19 serum level prior to RTX infusion for the long term maintenance of therapeutic response, and it´s utility as a biomarker for optimization in RA patients treated with RTX.

Methods: all RA patients treated with RTX in our center during 2016 and 2017 for at least 6 months, and with 12 months follow-up, were included. Demographic data, clinical data related to RA, including activity parameters (DAS28, HAQ, ESR, RCP), number of infections, optimization and serum levels of lymphocytic subpopulations (CD19, CD3 and CD56) and immunoglobulins (Ig) prior to each RTX cycle were collected. Optimization was defined as any dose decrease (lower dose for cycle and/or increase interval between cycles). Recurrent infections were defined as three or more infections per year. Descriptive statistics, correlation between basal levels of CD19, CD3 or CD56, and activity parameters or Ig levels at 6, 12 and 18 months, and association studies between lymphocyte subpopulations and optimization or recurrent infections were performed.

Results: Thirty patients (25 females, 55±11 years) with RA (24 RF/aCCP +, 13±9 years from disease onset), were included. At RTX initiation, DAS28 was 5.4±1.2, 28 patients (93%) were treated with any DMARD, 25 (83%) with prednisone (5±2 mg/d), and 19 (63%) had received previous biologic therapy. After 57±39 months of RTX (accumulated dose 14±10g), 22 patients had been optimized (at 37±32 months, DAS28 3.2±1.4) and 6 had stopped RTX. CD19 levels were lower than 2% in 22 patients (79%), including 9 with undetectable levels. CD19 levels (cells/mm³) were lower in optimized patients (21 vs 4, p=.02), and were correlated with DAS28 6 and 12 months later (r=0.4; p=.02), and with ESR 6 months later (r=0.6; p=.002). CD19 levels did not correlate with Ig levels, and were not associated with recurrent infections. CD3 and CD56 levels did not show any relevant association.

Conclusion: In RA patients treated with RTX for more than 12 months, CD19 levels correlate with long term therapeutic response, being low or undetectable levels predictors of good outcome, without association with Ig levels or increased infections. Our results suggest that CD19 levels before every RTX cycle might be a useful biomarker to select candidate patients for optimization with this therapy.

1. Cohen SB, Emery P. et al. Arthritis Rheum 2015;54:2793-2806
2. Bredemeier M, et al. Clin Rheumatol 2015;34:1801-1805.
3. Cambridge G et al. J Autoimmun 2016;70:22-30.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/predictive-value-of-cd19-serum-levels-for-long-term-therapeutic-response-and-utility-as-biomarker-for-optimization-in-rheumatoid-arthritis-patients-treated-with-rituximab/