Response to Rituximab and Timeframe to Relapse in Rheumatoid Arthritis Patients
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Response to Rituximab and Timeframe to Relapse in Rheumatoid Arthritis Patients Association with B-Cell Markers Athina Pyrpasopoulou,1 Stella Douma,1 Areti Triantafyllou,1 Elisavet Simoulidou,1 Magda Samara,2 Efthymia Parapanisiou2 and Spyros Aslanidis1 1 2nd Propedeutic Department of Internal Medicine, Hippokration General Hospital, Thessaloniki, Greece 2 Laboratory of Immunology, Hippokration General Hospital, Thessaloniki, Greece
Abstract
Objective: Rituximab is used to deplete B cells and control disease activity, mainly in patients with rheumatoid arthritis (RA) who have not responded to anti-tumor necrosis factor (TNF) therapy. Response rates and time to relapse vary significantly among treated individuals. The objective of this study was to monitor the response of seropositive and seronegative RA patients to rituximab and correlate relapse with B-cell markers in the two groups. Methods: Seventeen RA patients (eight seropositive for rheumatoid factor [RF+] and nine seronegative [RF-]) were treated with two cycles of rituximab. After treatment, all patients were re-evaluated at the outpatient clinic, and rituximab was readministered when disease relapse was confirmed by clinical-laboratory measures (Disease Activity Score [DAS]-28). CD20+ cells and CD20 receptor expression levels were estimated at initiation, relapse, and re-evaluation timepoints, and were compared between the two groups. Results: Seropositive patients responded favorably to treatment compared with the seronegative group. The mean time to relapse was 337.5 – 127.0 days for the RF+ patients versus 233.3 – 59.6 days for the RFpatients (p = 0.043), despite more aggressive concomitant treatment in the seronegative group. The DAS28 decrease 3 months after treatment was 1.695 – 1.076 in seropositive patients versus 0.94 – 1.62 in seronegative patients. At relapse, CD20 receptor expression (molecules/cell) was higher in RF+ patients than in their RF- counterparts, despite a significantly lower percentage of CD20+ cells. Conclusion: Rituximab treatment is efficient in both seropositive and seronegative RA. However, seropositive RA patients tend to respond favorably compared with seronegative patients. The differential CD20 receptor expression in the two groups at relapse potentially suggests a different pathogenetic mechanism of relapse and merits further investigation.
B cells have been recently selected as therapeutic targets for the treatment of rheumatoid arthritis (RA), due to their pleiotropic functions in autoimmune-mediated inflammatory pathways.[1] Differentiated plasma cells secrete auto-antibodies (to IgGrheumatoid factor [RF], citrullinated peptides, and the RA 33 kDa antigen). Autoantibodies, in turn, generate immune complexes that activate constant fragment (Fc) receptors and the complement to induce production of proinflammatory cytokines. Apart from antibody production, activated B cells act as antigenpresenting cells and interact with other cell types to pe
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