scholarly journals Longterm Effects of Rituximab on B Cell Counts and Autoantibody Production in Rheumatoid Arthritis: Use of High-sensitivity Flow Cytometry for More Sensitive Assessment of B Cell Depletion

2013 ◽  
Vol 40 (5) ◽  
pp. 565-571 ◽  
Author(s):  
Andrea Váncsa ◽  
Zoltán Szabó ◽  
Szilvia Szamosi ◽  
Nóra Bodnár ◽  
Edit Végh ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Flow Cytometry ◽  
Disease Activity ◽  
B Cell ◽  
Clinical Response ◽  
High Sensitivity ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Autoantibody Production ◽  
Cell Numbers

Objective.To assess the efficacy and safety of longterm rituximab (RTX) therapy for rheumatoid arthritis (RA) and study correlations among B cell depletion, clinical response, and autoantibody production.Methods.Seventy-seven patients with moderate or high RA activity received RTX and were re-treated every 6 months regardless of clinical response. All patients received at least 5 cycles. We assessed 28-joint Disease Activity Score (DAS28), IgM rheumatoid factor (RF), and anticitrullinated protein antibody (ACPA) levels at baseline, after 15 days, and then every 6 months for 24 months. Absolute CD19+ B lymphocyte counts were determined in 50 patients using high-sensitivity flow cytometry (hsFACS) by reading 100,000 events.Results.After 6, 12, 18, and 24 months, 51.6%, 51.9%, 73.3%, and 83.8% of patients, respectively, showed good European League Against Rheumatism responses. Significant and sustained decreases in IgM RF and ACPA levels were observed as early as 6 months and 12 months, respectively. The baseline mean absolute B cell number was 0.234 g/l. B cell numbers diminished significantly after the very first infusion by Day 15 (0.104 g/l; p = 0.007); they further decreased until 24 months (0.0013 g/l; p < 0.001). One RTX infusion resulted in incomplete depletion in 76.7% of patients. Upon RTX treatment, changes in CD19+ B cell numbers positively correlated with changes in DAS28 (r = 0.963, p = 0.008) and IgM RF (r = 0.859, p = 0.028), but not with changes in ACPA production (r = 0.726, p = 0.102). The correlations between B cell numbers and DAS28 were observed in both ACPA-seropositive (r = 0.999, p < 0.0001) and ACPA-negative patient subpopulations (r = 0.962, p = 0.009). The correlation between CD19+ cell numbers and IgM RF was observed only in the ACPA-positive population (r = 0.944, p = 0.005) but not in seronegative patients (r = 0.398, p = 0.435). No safety issues arose.Conclusion.In RA, clinical response to RTX is associated with the extent of B cell depletion and with autoantibody production. Changes in CD19+ B cell numbers correlate with those in disease activity and, in seropositive patients, also with IgM RF, but not with ACPA production. We found that hsFACS may be a useful method to more accurately assess incomplete B cell depletion.

scholarly journals B cell depletion treatment decreases Th17 cells in patients with rheumatoid arthritis

2021 ◽  
Author(s):  
Constantina A. Bounia ◽  
Stamatis-Nick C Liossis
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
B Cell ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Treg Cells ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Das28 Score ◽  
Autoimmune Rheumatic Diseases

Abstract Introduction: We aimed to evaluate for any possible effects of treatment with rituximab (RTX) on the peripheral Th17 and Treg subpopulations in patients with rheumatoid arthritis (RA).Patients and methods: We analyzed 16 patients with RA initiating RTX treatment, 11 patients with RA initiating abatacept treatment, 11 patients with RA treated with other medications, 8 patients with other autoimmune rheumatic diseases initiating RTX, and 14 healthy volunteers. Th17 cells (CD4+IL23R+IL17A+) and Treg cells (CD4+CD25hiFoxP3+) were evaluated flow-cytometrically.Results: Th17 cells from patients treated with RTX decreased significantly at weeks 8 and 16 (mean ± SEΜ: 3.01% ± 0.54℅ CD4+ cells at week 0 vs. 1.53% ± 0.24℅ at week 8 vs 1.10% ± 0.20℅ at week 16, p = 0.0004). Reductions of Th17 cells were evident in:clinical responders (DAS28 score ≤ 3.2), ACPA (+) and RF (-) patients; circulating Tregs remained stable. Th17 and Tregs were not affected by ABA treatment or by changes in disease activity. Tregs, but not Th17 cells, decreased following treatment with RTX in patients with other autoimmune diseases (0.75% ± 0.16% at week 0 vs. 0.43% ± 0.16% at week 8, p = 0.033).Conclusion: RTX-induced B cell depletion results in a significant reduction of circulating Th17 cell percentages, whereas it has no effect on Tregs of patients with RA. This reduction of Th17 cells was evident particularly in responders to RTX treatment, ACPA+ and RF (-) patients with RA.

scholarly journals AB0223 MODIFIED DOSE RITUXIMAB BIOSIMILAR IN RHEUMATOID ARTHRITIS COMPARING B-CELL DEPLETION EFFECT AND DISEASE ACTIVITY SCORES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1137.2-1138
Author(s):  
S. Bandyopadhyay
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
B Cell ◽  
Low Dose ◽  
Outcome Measurement ◽  
Eligible Patient ◽  
Cell Depletion ◽  
Individual Choice ◽  
B Cell Depletion ◽  
Eular Response

Background:In emerging economies self-funding patients opt for less costly options, influencing both compliance and maintenance of treatment for chronic illness. Studies comparing originator rituximab 1000mgx2 and 500mgx2 doses in Rheumatoid arthritis (RA) have yielded interesting results1. Evidence of B cell depletion, measured by CD19 count, maybe a marker for disease improvement2. However effect of different dose of biosimilar Rituximab (bRTX) on B cell depletion and disease activity needs exploration.Objectives:To determine correlation of CD19 count defining B cell depletion and disease activity with different dosages of bRTX treatment.Methods:Between April 2019 and March 2020, all RA patients with DMARD failure were screened for eligibility of biologics as routine clinical practice. Depending on individual choice, after full consent, patients received either 1000mgx2 or 500mgx2 bRTX. All patients had CD19 count before and 12 months after the first dose. Effectiveness of bRTX 1000 mg×2 and 500 mg×2 was assessed by DAS28 and EULAR response. Comparative adjusted analysis was performed by analysis of variance (ANOVA).Results:Out of 468 eligible patient, 84 opted for biologic. Of which 27 patients consented for bRTX (17 female, mean age 39.5 years).13 patients opted for 1000mg×2 and 14 for 500mg×2 dose. 74% (20/27) patients were on concomitant methotrexate and 26% on hydroxychloroquine (7/27). Both doses led to significant reduction in ESR, CRP, and DAS28-ESR at 12 months (p<0.001) (Table 1).Table 1.RA outcome-measurement scores at 12 months post biosimilar Rituximab therapy.VariableBaseline12 monthsRTX 1000mg x 2(n=13)RTX 500mg x 2(n=14)RTX 1000mg x 2(n=13)RTX 500mg x 2(n=14)ESR*53.9±23.957.1±24.723.9±2.924.1±4.7CRP*6.1±3.96.9±2.92.1±0.92.3±0.9DAS28-ESR*6.1±0.36.1±0.24.0±0.44.1±0.2CD 19+ Count*# (105/L)1191.6±308.41155±289.6128.8±90.4139±90.6* p<0.0001 as compared to 12 mos vs baseline; # p<0.0001 as compared amongst groupAt the end of 12 months, compared to 1000mg, CD19 count was higher in 500mg group (p=0.25). Percentage of patients achieving EULAR moderate or no response was higher in 500mg group (37%vs29%, p=0.205), both complete and incomplete B cell depletion, but patients achieving good response was same in both groups (14.8%vs18.5%, p = 0.25). (Figure 1).Figure 1.EULAR Response at 12 monthsConclusion:Low dose bRTX is effective in DMARD refractory RA patients with similar improvements as regular dose, although CD19 depletion was less in low dose group. A larger study to establish radiographic regression with CD19 depletion and disease activity score can help in further strengthening the use of lower dose bRTX in RA leading to significant economic advantage.References:[1]Chatzidionysiou K, Lie E, Nasonov E, Lukina G,et al. Rheumatic Diseases Portuguese Register. Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort: data from the CERERRA collaboration. Arthritis Res Ther. 2016 Feb 16;18:50.[2]Vital EM, Rawstron AC, Dass S, Henshaw K, Madden J, Emery P, McGonagle D. Reduced-dose rituximab in rheumatoid arthritis: efficacy depends on degree of B cell depletion. Arthritis Rheum. 2011 Mar;63(3):603-8.Disclosure of Interests:None declared

An extra dose of rituximab improves clinical response in rheumatoid arthritis patients with initial incomplete B cell depletion: a randomised controlled trial

2014 ◽  
Vol 74 (6) ◽  
pp. 1195-1201 ◽  
Author(s):  
Edward M Vital ◽  
Shouvik Dass ◽  
Maya H Buch ◽  
Andrew C Rawstron ◽  
Paul Emery
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
B Cell ◽  
Clinical Response ◽  
Controlled Trial ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Double Blind ◽  
Acr20 Response ◽  
Randomised Controlled

ObjectivesSince clinical non-response to 2×1000 mg rituximab has previously been found to be associated with incomplete B cell depletion, we determined, in a randomised controlled proof of concept study, whether patients with initial incomplete B cell depletion would benefit from an additional infusion of rituximab at week 4.MethodsPatients with active rheumatoid arthritis despite methotrexate received a first infusion of rituximab 1000 mg and were tested for persistent B cells using highly sensitive flow cytometry on day 15. All received a second infusion of 1 g (according to license), but patients with persistent B cells were subsequently randomised double-blind to receive, 2 weeks later, either a third infusion of 1000 mg rituximab or placebo. Clinical response was determined by European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) criteria.ResultsBaseline characteristics were balanced between groups. Treatment with 3×1000 mg rituximab resulted in significantly greater depletion (lower B cell and plasmablast numbers between 8 and 28 weeks) paralleled by significantly better EULAR and ACR20 response rates at 40 weeks (p=0.035 and p=0.027, respectively) and 52 weeks (p=0.021 and p=0.043, respectively) compared with 2×1000 mg. Immunoglobulin titres remained stable in both arms, and adverse event rates were balanced.ConclusionsIn rituximab-treated patients with incomplete B cell depletion (predictive of poor response), an extra 1000 mg infusion of rituximab at 4 weeks produced both better depletion and clinical responses than placebo with no worsening of safety. Degree of depletion is an important, but modifiable, determinant of response.

Statins do not influence clinical response and B cell depletion after rituximab treatment in rheumatoid arthritis

2012 ◽  
Vol 72 (3) ◽  
pp. 463-464 ◽  
Author(s):  
Sudipto Das ◽  
Meritxell Fernandez Matilla ◽  
Shouvik Dass ◽  
Maya H Buch ◽  
Andrew C Rawstron ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cell ◽  
Clinical Response ◽  
Cell Depletion ◽  
B Cell Depletion
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