期刊
DIABETES CARE
卷 37, 期 2, 页码 453-459出版社
AMER DIABETES ASSOC
DOI: 10.2337/dc13-0626
关键词
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资金
- National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Allergy and Infectious Diseases
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 DK-061010, U01 DK-061016, U01 DK-061034, U01 DK-061036, U01 DK-061040, U01 DK-061041, U01 DK-061042, U01 DK-061055, U01 DK-061058, U01 DK-084565, U01 DK-085453, U01 DK-085461, U01 DK-085463, U01 DK-085466, U01 DK-085499, U01 DK-085505, U01 DK-085509, HHSN267200800019C]
- National Center for Research Resources, through Clinical Translational Science Awards [UL1 RR024131, UL1 RR024139, UL1 RR024153, UL1 RR024975, UL1 RR024982, UL1 RR025744, UL1 RR025761, UL1 RR025780, UL1 RR029890, UL1 RR031986]
- General Clinical Research Center [M01 RR00400]
- Juvenile Diabetes Research Foundation International
- American Diabetes Association
OBJECTIVEWe previously reported that selective depletion of B-lymphocytes with rituximab, an anti-CD20 monoclonal antibody, slowed decline of -cell function in recent-onset type 1 diabetes mellitus (T1DM) at 1 year. Subjects were followed further to determine whether there was persistence of effect.RESEARCH DESIGN AND METHODSEighty-seven subjects (aged 8-40 years) were randomly assigned to, and 81 received, infusions of rituximab or placebo on days 1, 8, 15, and 22. The primary outcomebaseline-adjusted mean 2-h area under the curve (AUC) serum C-peptide during a mixed-meal tolerance test (MMTT) at 1 yearshowed higher C-peptide AUC with rituximab versus placebo. Subjects were further followed with additional MMTTs every 6 months.RESULTSThe rate of decline of C-peptide was parallel between groups but shifted by 8.2 months in rituximab-treated subjects. Over 30 months, AUC, insulin dose, and HbA(1c) were similar for rituximab and placebo. However, in evaluating change in C-peptide over the entire follow-up period, the rituximab group means were significantly larger as compared within assessment times with the placebo group means using a global test (P = 0.03). Odds ratio for loss of C-peptide to <0.2 nmol/L following rituximab was 0.565 (P = 0.064). B-lymphocytes recovered to baseline values by 18 months. Serum IgG levels were maintained in the normal range but IgM levels were depressed.CONCLUSIONSLike several other immunotherapeutic approaches tested, in recent-onset T1DM, rituximab delays the fall in C-peptide but does not appear to fundamentally alter the underlying pathophysiology of the disease.
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