Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: TNF blockade is a mainstay of treatment for rheumatoid arthritis (RA), but a significant proportion of patients fail to respond to treatment or lose clinical response over time. B cells play a critical role in the disease process and can become activated in germinal center (GC) reactions in secondary lymphoid tissue and ectopic GCs in synovium. TNF and lymphotoxin (LT) blockade have been shown to alter GC reactions in mouse models, but the potential impact of anti-TNF therapy on the B cell compartment remains controversial. The purpose of this study is to characterize the peripheral B cell compartment longitudinally during anti-TNF therapy in RA and determine the relationship between B cells and treatment response.
Methods: We randomized subjects in a 2:1 ratio to receive standard dosing regimens of etanercept or adalimumab for 24 weeks. Eligible subjects met the 1987 ACR criteria for RA, had clinically active RA (DAS28>4.4), and were on methotrexate. Disease activity and response was assessed based on DAS28-CRP. B cells from 54 patients were analyzed by multi-color flow cytometry at baseline and longitudinally at 12 and 24 weeks. The primary endpoint was the change in memory B cell fraction in the peripheral blood from baseline to week 12. All B cell results are expressed as a mean percent (+/- SE) of the CD19+ or parent population.
Results: Of the 63 eligible subjects, 43 and 20 were randomized to etanercept and adalimumab, respectively. The mean DAS at baseline was 5.3. After 12 weeks of treatment, 43% (n=24) of patients were identified as good responders, 45% (n=25) moderate responders, and 13% (n=7) non-responders (NR). The primary endpoint was not met as B cell subsets remained remarkably stable over the course of the study regardless of treatment group, and the remainder of the results report secondary endpoints. Repeated measures analysis of variance (with unstructured covariance) was used to compare trends over time between NR and moderate or good responders (R). In NRs, the mean % CD27-IgD- (DN) memory B cells was significantly higher than R over all visits (R: baseline 6.2±0.4, WK12: 5.3±0.4, WK24: 5.1±0.4; NR: baseline: 8.7±1.1, WK12: 8.6±1.1, WK24: 7.6±1.1; p=0.01 over all visits, p<0.05 by visit). There was a significantly higher frequency of CD21- activated B cells over all visits in both SM (NR: baseline 11.8±2.1, WK12 13.9±1.9, WK24 15.2±2.3; R: baseline 8.5±0.8, WK12 8.7±0.7, WK24 8.6±0.8, p=0.02 over all visits, p<0.05 at WK12, WK24) and DN B cells (NR: baseline 36±5.2, WK12 34.1±4.6, WK24 37.5±4.8; R: baseline 19.0±2.0, WK12 19.1±1.7, WK24 19.0±1.8, p=0.001 over all visits, p<0.05 at each visit) in NRs vs. Rs.
Conclusion: Our results suggest a relationship between activated memory B cells and the response to anti-TNF treatment, with higher activated memory associated with a less robust response. Examination of peripheral lymphoid and target tissue may be necessary to define changes in B cell subsets with anti-TNF.
To cite this abstract in AMA style:Barnard J, Meednu N, Callahan K, Coca A, Marston BA, Thiele RG, Tabechian D, Bolster M, Curtis JR, Mackay MC, Graf JD, Keating R, Smith E, Boyle K, Keyes-Elstein L, Welch B, Goldmuntz E, Anolik JH. Activated Memory B Cells in Rheumatoid Arthritis and Relationship to Anti-TNF Treatment [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/activated-memory-b-cells-in-rheumatoid-arthritis-and-relationship-to-anti-tnf-treatment/. Accessed September 18, 2020.
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