This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.

Objective. Rituximab appears to be effective in many studies of systemic lupus erythematosus (SLE), with variable initial clinical response and time to relapse. However, results of a randomized controlled trial of rituximab were negative. This study was undertaken to evaluate the effectiveness of rituximab in SLE, using highly sensitive flow cytometry (HSFC), which can define B cell numbers 50-100 times lower than conventional techniques and predicts responses in rheumatoid arthritis.Methods. Thirty-nine patients with active SLE were started on a standard regimen of rituximab with intravenous and oral steroids. Clinical response and relapse were defined using the British Isles Lupus Assessment Group (BILAG) index with criteria for major clinical response, partial clinical response, and nonresponse. HSFC, including analysis of B cell subsets, was performed.Results. There was a significant reduction from baseline in global BILAG score at all time points analyzed (P < 0.0001), and major clinical response and partial clinical response rates were 51% and 31%, respectively. Time to relapse was highly variable. Fifty percent of the patients relapsed after 6-18 months (earlier relapse); the remainder relapsed at a slower rate (later relapse). B cell depletion and repopulation were variable and were predictive of these clinical outcomes. There was a persistent B cell presence in 21 patients after 2 infusions of rituximab, which included all 7 patients with no response (P ‫؍‬ 0.012 versus patients with complete depletion of B cells). Memory B cell (P ‫؍‬ 0.02) and plasmablast (P < 0.001) repopulation after 26 weeks was markedly faster in patients with earlier relapse versus patients with later relapse.Conclusion. Our findings indicate that rituximab is effective in SLE, and clinical responses are supported by close correlation with B cell numbers. HSFC is a valuable tool in the assessment and prediction of response in SLE.

Objective. In rheumatoid arthritis (RA), B cell depletion occurs in all patients treated with rituximab, but the clinical responses to rituximab are variable. A highly sensitive assay was used to test the hypothesis that B cell depletion is variable, and that incomplete depletion leads to a poorer outcome.Methods. Sixty patients with active RA unresponsive to anti-tumor necrosis factor agents received two 1-gram infusions of rituximab. B cell numbers were measured by highly sensitive flow cytometry before and after each infusion and at 3-month intervals thereafter. A reduction in B cell levels below 0.0001 ؋ 10 9 /liter was defined as complete depletion (compared with 0.05 ؋ 10 9 /liter by conventional cytometry). Clinical responses were measured using the European League Against Rheumatism (EULAR) criteria.Results. At 6 months, 92% of patients had a moderate-to-good clinical response according to the EULAR criteria. B cells were detected in 63% of patients after the first infusion of rituximab (median level 0.0009 ؋ 10 9 /liter [range <0.0001-0.0015 ؋ 10 9 /liter), and these patients had poorer clinical outcomes than patients with complete depletion. At 9 months, 82% of patients with complete depletion had a moderate-togood EULAR response, compared with 43% of those with partial depletion (P ‫؍‬ 0.01). At 12 months, 59% of complete responders had a moderate-to-good EULAR response, compared with 21% of those with partial depletion (P ‫؍‬ 0.01). Patients in whom B cells were depleted only after the second infusion did no better than those in whom depletion was never complete and had poorer clinical outcomes than those in whom depletion was initially complete.Conclusion. This study is the first to show, using a highly sensitive analysis, that rituximab therapy is associated with variable diminution in B cell numbers. A lack of complete depletion of B cells after 1 infusion was associated with a poorer outcome.