TY - JOUR
T1 - Reactivation of latent viruses in individuals receiving rituximab for new onset type 1 diabetes
AU - Kroll, Jing Lu
AU - Beam, Craig
AU - Li, Shaobing
AU - Viscidi, Raphael
AU - Dighero, Bonnie
AU - Cho, Alice
AU - Boulware, David
AU - Pescovitz, Mark
AU - Weinberg, Adriana
N1 - Funding Information:
This study was funded by grant number 1RC4DK090912-01 from National Institutes of Diabetes and Digestive and Kidney Disorders (NIDDK) . The sponsor of the parent trial was the Type 1 Diabetes TrialNet Study Group. Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health (NIH) through the NIDDK , the National Institute of Allergy and Infectious Diseases , and The Eunice Kennedy Shriver National Institute of Child Health and Human Development , through the cooperative agreements U01 DK061010 , U01 DK061016 , U01 DK061034 , U01 DK061036 , U01 DK061040 , U01 DK061041 , U01 DK061042 , U01 DK061055 , U01 DK061058 , U01 DK084565 , U01 DK085453 , U01 DK085461 , U01 DK085463 , U01 DK085466 , U01 DK085499 , U01 DK085505 , U01 DK085509 , and a contract HHSN267200800019C ; the 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 , P30 DK017047 , and General Clinical Research Center Award M01 RR00400 ; the Juvenile Diabetes Research Foundation International (JRDF) ; and the American Diabetes Association (ADA) . The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, JDRF, or ADA.
PY - 2013/6
Y1 - 2013/6
N2 - Background: Rituximab has been successfully used as an experimental therapy in different autoimmune diseases. Recently, a double-blind placebo-controlled phase-2 study in early onset type 1 diabetes showed that rituximab delayed progression of the disease. However, like with any immunosuppressive therapy, there is a concern of opportunistic viral reactivations with the use of rituximab, including herpes and polyomaviruses. Objectives: To study the incidence of new infections and reactivations with BK, JC, Epstein-Barr and cytomegalovirus (BKV, JCV, EBV and CMV) in T1D participants in the phase-2 rituximab study. Study design: Subjects received 4 weekly doses of rituximab (N=57) or placebo (N=30) during the first month of study. Blood samples obtained at weeks 0, 12, 26, 56 and 78 were assayed for CMV, EBV, BKV and JCV by real-time DNA PCR and serology. Results: EBV reactivations were diagnosed by PCR in 25% of placebo, but none of rituximab recipients (p<0.01). There were no episodes of CMV viremia in either treatment group. BKV viremias were significantly more common in the rituximab recipients (9%) compared with placebo controls (0, p<0.01). No JCV reactivations were detected in this study, but among 6 rituximab and 2 placebo recipients who seroconverted for JCV during the study, only one rituximab recipient had detectable viremia. All infections were asymptomatic. Conclusions: Four doses of rituximab administered to individuals with early onset T1D decreased the incidence of asymptomatic EBV reactivations, as predicted by the rituximab-mediated elimination of memory B-cells, but increased the frequency of asymptomatic viremias caused by polyomaviruses.
AB - Background: Rituximab has been successfully used as an experimental therapy in different autoimmune diseases. Recently, a double-blind placebo-controlled phase-2 study in early onset type 1 diabetes showed that rituximab delayed progression of the disease. However, like with any immunosuppressive therapy, there is a concern of opportunistic viral reactivations with the use of rituximab, including herpes and polyomaviruses. Objectives: To study the incidence of new infections and reactivations with BK, JC, Epstein-Barr and cytomegalovirus (BKV, JCV, EBV and CMV) in T1D participants in the phase-2 rituximab study. Study design: Subjects received 4 weekly doses of rituximab (N=57) or placebo (N=30) during the first month of study. Blood samples obtained at weeks 0, 12, 26, 56 and 78 were assayed for CMV, EBV, BKV and JCV by real-time DNA PCR and serology. Results: EBV reactivations were diagnosed by PCR in 25% of placebo, but none of rituximab recipients (p<0.01). There were no episodes of CMV viremia in either treatment group. BKV viremias were significantly more common in the rituximab recipients (9%) compared with placebo controls (0, p<0.01). No JCV reactivations were detected in this study, but among 6 rituximab and 2 placebo recipients who seroconverted for JCV during the study, only one rituximab recipient had detectable viremia. All infections were asymptomatic. Conclusions: Four doses of rituximab administered to individuals with early onset T1D decreased the incidence of asymptomatic EBV reactivations, as predicted by the rituximab-mediated elimination of memory B-cells, but increased the frequency of asymptomatic viremias caused by polyomaviruses.
KW - BK virus
KW - Cytomegalovirus
KW - Epstein-Barr virus
KW - JC virus
KW - Rituximab
KW - Type 1 diabetes
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U2 - 10.1016/j.jcv.2013.01.016
DO - 10.1016/j.jcv.2013.01.016
M3 - Article
C2 - 23422292
AN - SCOPUS:84876960512
SN - 1386-6532
VL - 57
SP - 115
EP - 119
JO - Journal of Clinical Virology
JF - Journal of Clinical Virology
IS - 2
ER -