期刊
ARTHRITIS AND RHEUMATISM
卷 63, 期 10, 页码 3038-3047出版社
WILEY
DOI: 10.1002/art.30466
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资金
- National Institute for Health Research (NIHR)
- Roche
- Abbott
- Pfizer
- National Institutes of Health Research (NIHR) [RTF/01/097] Funding Source: National Institutes of Health Research (NIHR)
- Cancer Research UK
- Versus Arthritis [18475] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10299, RTF/01/097] Funding Source: researchfish
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.
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