THU0103 Synovial plasma cells predict relapse after rituximab therapy in rheumatoid arthritis
Authors: E. Vital, Y.M. El-Sherbiny, K. Henshaw, S. Dass, S. Das, M. Buch, F. Ponchel, P. Emery
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Response to rituximab in patients with RA is followed by relapse after a variable interval. Previous studies have associated initial response to rituximab with lower numbers of CD79a+ B cells at baseline and CD138+ plasma cells at 16 weeks. We recently demonstrated that numbers of plasmablasts, rheumatoid factor titre, and DAS28 at 6 months predicted subsequent outcome [1]. Synovial predictors of duration of response have not previously been described. <h3>Objectives</h3> To identify synovial predictors of response and relapse after rituximab <h3>Methods</h3> 25 patients received 2×1000 mg rituximab in combination with 2×100 mg methylprednisolone and oral methotrexate. Synovial biopsy was performed before, and either 16 (n=16) or 26 (n=9) weeks after rituximab. Sections were stained to identify Plasma cells (CD138), B cells (CD19, CD20cy), T cells (CD3) and macrophages (CD68) and analysed by digital image analysis. Clinical response was categorised by EULAR response criteria at 6 months. Patients with EULAR moderate or good response at 6 months were categorised at 12 months as relapse (EULAR non-response) or non-relapse (EULAR moderate or good response). Non-parametric statistical tests were used. <h3>Results</h3> At 6 months, EULAR non, moderate and good responses were achieved by 7 (28%), 9 (36%)and 9 (36%) patients respectively. Of the 18 patients with EULAR good or moderate response at 6 months, 6 (33%) had relapse at 12 months. In synovium, following rituximab there was a significant reduction in CD19/CD20cy (p=0.001) and CD3 (p=0.004), and no significant change in CD138 (p=0.506). Follow up biopsies collected at 16 or 26 weeks were compared. No significant differences in DAS28 or synovial markers were identified between these time points. <i>Post rituximab histology and response at 6 months:</i> No marker was significantly associated with EULAR response, other than a trend to higher CD68 in non-responders after treatment <i>Post rituximab histology and relapse at 12 months:</i> Comparing relapse and non-relapse groups, there was no difference in CD138 scores at baseline. In the no relapse group there was a trend to reduction in CD138 (p=0.060), whereas in the relapse group there was a trend to increase in CD138 (p=0.180), resulting in significantly higher post-rituximab CD138 scores in patients with relapse (p=0.047). CD138 after rituximab did not correlate with DAS28, but did correlate with RF titre (R=0.637). Patients with RF &gt;108 IU/mL (the level most predictive of relapse in our previous study) had significantly higher synovial CD138 after rituximab (p=0.010), despite no difference in DAS28 at 6 months (p=0.324). <h3>Conclusions</h3> After rituximab, synovial B cells are generally depleted efficiently. In contrast, synovial plasma cells were only partially reduced in a subset of patients, with high post-rituximab numbers predicting relapse The ability of the synovium to support and retain plasma cells is a determinant of clinical outcome of rituximab therapy. <h3>References</h3> Vital EM et al. Arthritis and Rheumatism 2011: 63(10):1643 <h3>Disclosure of Interest</h3> E. Vital Grant/Research support from: Roche, Speakers Bureau: Roche, Y. El-Sherbiny: None Declared, K. Henshaw: None Declared, S. Dass Speakers Bureau: Roche, S. Das: None Declared, M. Buch Speakers Bureau: Roche, F. Ponchel: None Declared, P. Emery Grant/Research support from: Roche, Speakers Bureau: Roche