AB0527 Prediction of improving responses on repeat cycles of rituximab using B cell biomarkers:
Authors: S. Das, E. Vital, S. Dass, M.H. Buch, A.C. Rawstron, P. Emery
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rituximab is effective in rheumatoid arthritis but many patients do not achieve EULAR Good response. We previously showed that repeat cycles of rituximab improve response in patients with non-response (NR) to the first cycle (C1)[1]. <h3>Objectives</h3> To identify predictors of changing clinical response following retreatment with rituximab. <h3>Methods</h3> 124 patients pooled from four clinical trials were treated with 2×1000mg of rituximab at baseline and then, in initial responders, on clinical relapse. DAS28 and EULAR response were calculated at baseline and 6 months after each cycle, compared to the original baseline. B cell naïve, memory and plasmablast subsets were measured by high sensitivity flow cytometry as previously described. <h3>Results</h3> Patients with C1-NR were retreated at 6mo. Patients with C1-MOD or C1-GOOD were retreated following clinical relapse. Overall responses were better in C2 compared to C1. The C1-NR cohort included 25 patients previously reported, and 15 additional patients. 18/25 (72%) of the previously reported cohort, and 7/15 (47%) of the additional patients responded to C2. Response to C2 was associated with significantly higher numbers of B cells at retreatment (p=0.012), but no difference in DAS28 or its components. For patients with moderate or good response in C1, response to retreatment on relapse is shown below. In C1-MOD, B cell numbers were significantly lower at weeks 2-14 in C2 compared to C1. In C1-GOOD, no difference was observed between cycles. Of 78 patients with positive RF at baseline, 28% became negative after C1 (seroconversion). Seroconversion was associated with significantly lower B cell numbers at weeks 2-26 in C1. Seroconversion was not associated with response in C1, but was associated with improving response in C2. In patients with C1-MOD and positive RF at baseline, 11/33 had seroconversion in C1, of whom only 1(9%) improved to GOOD in C2. Of 22/33 without seroconversion, 9(41%) improved to GOOD in C2 (p=0.012). Finally, we looked for factors predicting worsening response. DAS28 at relapse, degree of B cell repopulation or degree of B cell depletion did not differ between patients with stable/improved responses and those with worsening response. However, patients with worsening response had significantly lower DAS28 at baseline C1 (p=0.015), mostly explained by lower CRP (p=0.006). Notably, of patients with CRP&gt;10 at baseline C1, 92% had stable or improved response on C2. <h3>Conclusions</h3> After rituximab, some non- or moderate responders have markers of continuing B cell activity (rapid B cell repopulation and persistent autoantibodies). These patients have potential for improved responses with repeat cycles of B cell depletion. Retreatment at 6 months should be considered in patients with non-response, or those with moderate response and persistently positive RF. Patients who become seronegative seldom improve further. Patients with high CRP before C1 seldom lose response during C2. <h3>References</h3> Vital EM et al. Arthritis Rheum. 2010 May;62(5):1273-9. <h3>Disclosure of Interest</h3> S. Das: None Declared, E. Vital Grant/Research support from: Roche, Speakers Bureau: Roche, S. Dass Speakers Bureau: Roche, M. Buch Speakers Bureau: Roche, A. Rawstron: None Declared, P. Emery Grant/Research support from: Roche, Speakers Bureau: Roche