PMID- 24026563 OWN - NLM STAT- MEDLINE DCOM- 20141128 LR - 20211021 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 37 IP - 2 DP - 2014 Feb TI - B-lymphocyte depletion with rituximab and beta-cell function: two-year results. PG - 453-9 LID - 10.2337/dc13-0626 [doi] AB - OBJECTIVE: We previously reported that selective depletion of B-lymphocytes with rituximab, an anti-CD20 monoclonal antibody, slowed decline of beta-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 METHODS: Eighty-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 outcome-baseline-adjusted mean 2-h area under the curve (AUC) serum C-peptide during a mixed-meal tolerance test (MMTT) at 1 year-showed higher C-peptide AUC with rituximab versus placebo. Subjects were further followed with additional MMTTs every 6 months. RESULTS: The 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 HbA1c 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. CONCLUSIONS: Like 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. FAU - Pescovitz, Mark D AU - Pescovitz MD AD - Corresponding author: Jay S. Skyler, jskyler@miami.edu. FAU - Greenbaum, Carla J AU - Greenbaum CJ FAU - Bundy, Brian AU - Bundy B FAU - Becker, Dorothy J AU - Becker DJ FAU - Gitelman, Stephen E AU - Gitelman SE FAU - Goland, Robin AU - Goland R FAU - Gottlieb, Peter A AU - Gottlieb PA FAU - Marks, Jennifer B AU - Marks JB FAU - Moran, Antoinette AU - Moran A FAU - Raskin, Philip AU - Raskin P FAU - Rodriguez, Henry AU - Rodriguez H FAU - Schatz, Desmond A AU - Schatz DA FAU - Wherrett, Diane K AU - Wherrett DK FAU - Wilson, Darrell M AU - Wilson DM FAU - Krischer, Jeffrey P AU - Krischer JP FAU - Skyler, Jay S AU - Skyler JS CN - Type 1 Diabetes TrialNet Anti-CD20 Study Group LA - eng SI - ClinicalTrials.gov/NCT00279305 GR - UL1 RR024139/RR/NCRR NIH HHS/United States GR - U01 DK-085509/DK/NIDDK NIH HHS/United States GR - U01DK-085505/DK/NIDDK NIH HHS/United States GR - U01 DK-061036/DK/NIDDK NIH HHS/United States GR - U01 DK061055/DK/NIDDK NIH HHS/United States GR - U01 DK-061040/DK/NIDDK NIH HHS/United States GR - U01 DK061036/DK/NIDDK NIH HHS/United States GR - UL1 RR024982/RR/NCRR NIH HHS/United States GR - UL1 TR001085/TR/NCATS NIH HHS/United States GR - U01 DK061042/DK/NIDDK NIH HHS/United States GR - U01 DK-085453/DK/NIDDK NIH HHS/United States GR - UC4 DK097835/DK/NIDDK NIH HHS/United States GR - U01 DK085476/DK/NIDDK NIH HHS/United States GR - M01 RR000400/RR/NCRR NIH HHS/United States GR - UL1RR031986/RR/NCRR NIH HHS/United States GR - UL1 TR000005/TR/NCATS NIH HHS/United States GR - U01 DK061010/DK/NIDDK NIH HHS/United States GR - UL1 RR025761/RR/NCRR NIH HHS/United States GR - P30 DK063720/DK/NIDDK NIH HHS/United States GR - U01 DK061040/DK/NIDDK NIH HHS/United States GR - UL1 RR024153/RR/NCRR NIH HHS/United States GR - UL1 RR029890/RR/NCRR NIH HHS/United States GR - UL1 TR001105/TR/NCATS NIH HHS/United States GR - UL1 RR031986/RR/NCRR NIH HHS/United States GR - U01 DK085466/DK/NIDDK NIH HHS/United States GR - U01 DK061058/DK/NIDDK NIH HHS/United States GR - U01 DK085505/DK/NIDDK NIH HHS/United States GR - U01 DK085453/DK/NIDDK NIH HHS/United States GR - UL1 RR025780/RR/NCRR NIH HHS/United States GR - U01 DK-061010/DK/NIDDK NIH HHS/United States GR - U01 DK-061058/DK/NIDDK NIH HHS/United States GR - U01 DK-085461/DK/NIDDK NIH HHS/United States GR - UL1 RR024131/RR/NCRR NIH HHS/United States GR - U01 DK-085499/DK/NIDDK NIH HHS/United States GR - DP3 DK097681/DK/NIDDK NIH HHS/United States GR - U01 DK-084565/DK/NIDDK NIH HHS/United States GR - U01 DK085499/DK/NIDDK NIH HHS/United States GR - UL1 TR000093/TR/NCATS NIH HHS/United States GR - U01 DK-061042/DK/NIDDK NIH HHS/United States GR - U01 DK085463/DK/NIDDK NIH HHS/United States GR - UL1 TR001108/TR/NCATS NIH HHS/United States GR - U01 DK-061034/DK/NIDDK NIH HHS/United States GR - U01 DK-085466/DK/NIDDK NIH HHS/United States GR - UL1 RR025744/RR/NCRR NIH HHS/United States GR - U01DK-061055/DK/NIDDK NIH HHS/United States GR - HHSN267200800019C/DK/NIDDK NIH HHS/United States GR - U01 DK061034/DK/NIDDK NIH HHS/United States GR - UL1 TR001082/TR/NCATS NIH HHS/United States GR - U01 DK085461/DK/NIDDK NIH HHS/United States GR - U01 DK085509/DK/NIDDK NIH HHS/United States GR - U01 DK-085463/DK/NIDDK NIH HHS/United States GR - UL1 RR024975/RR/NCRR NIH HHS/United States GR - U01 DK-061041/DK/NIDDK NIH HHS/United States GR - U01 DK061041/DK/NIDDK NIH HHS/United States GR - M01 RR00400/RR/NCRR NIH HHS/United States GR - UC4 DK117009/DK/NIDDK NIH HHS/United States GR - UL1 TR002529/TR/NCATS NIH HHS/United States GR - U01 DK-061016/DK/NIDDK NIH HHS/United States GR - P30 DK017047/DK/NIDDK NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural DEP - 20130911 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Antibodies, Monoclonal, Murine-Derived) RN - 0 (Placebos) RN - 4F4X42SYQ6 (Rituximab) SB - IM MH - Adolescent MH - Adult MH - Antibodies, Monoclonal, Murine-Derived/*therapeutic use MH - Area Under Curve MH - B-Lymphocytes/*immunology MH - Child MH - Diabetes Mellitus, Type 1/*therapy MH - Female MH - Humans MH - Islets of Langerhans/*physiopathology MH - Lymphocyte Depletion/*methods MH - Male MH - Placebos MH - Rituximab MH - Young Adult PMC - PMC3898764 EDAT- 2013/09/13 06:00 MHDA- 2014/12/15 06:00 PMCR- 2015/02/01 CRDT- 2013/09/13 06:00 PHST- 2013/09/13 06:00 [entrez] PHST- 2013/09/13 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] PHST- 2015/02/01 00:00 [pmc-release] AID - dc13-0626 [pii] AID - 0626 [pii] AID - 10.2337/dc13-0626 [doi] PST - ppublish SO - Diabetes Care. 2014 Feb;37(2):453-9. doi: 10.2337/dc13-0626. Epub 2013 Sep 11.