Reactivation of latent viruses in individuals receiving rituximab for new onset
type 1 diabetes.
Author(s): Kroll JL(1), Beam C, Li S, Viscidi R, Dighero B, Cho A, Boulware D, Pescovitz M,
Weinberg A; Type 1 Diabetes TrialNet Anti CD-20 Study Group.
Collaborators: Skyler JS, Greenbaum CJ, Kenyon NS, Rafkin-Mervis L, Sosenko JM,
Lachin JM, Krause-Steinrauf H, McGee PF, Hess K, Raiden E, Fradkin J, Leschek E,
Savage P, Spain L, Blumberg E, Braun J, Laffel L, Naji A, Nerup J, Orchard T,
Tsiatis A, Veatch R, Wallace D, Lernmark A, Lo B, Mitchell H, Steffes M, Zinman
B, Loechelt B, Baden L, Green M, Weinberg A, Eisenbarth GS, Davis B, Marcovina S,
Palmer JP, Weinberg A, Winter W, Yu L, Davis B, Babu S, Davis B, Ochs HD,
Torgerson TR, Ocheltree E, Berger J, Koralnik I, Tyler K, Leschek RT, Pescovitz
MD, Buckingham B, Fathman C, Gitelman S, Herold K, Kenyon N, Krause-Steinrauf H,
Looney J, Lunney J, Ng D, Rodriguez H, Spain L, Greenbaum C, Lachin JM, Leschek
E, Skyler JS, Owens K, Greenbaum C, Bollyky J, Sanda S, McCulloch-Olson M, Hefty
D, Webber C, Kuhns K, Murphy C, Goland R, Greenberg E, Gallagher MP, Trast J,
Chan M, Rodriguez H, Pescovitz M, Christner L, Nicholson M, Mendez M, Wilson DM,
A B, Aye T, Esrey T, Soto A, Perry J, Baker B, Rigby A, Riley K, Chatav M, Berry
B, Gitelman SE, Rosenthal SM, Anderson M, Adi S, Breen K, Hamilton C, Gottlieb P,
Chase H, Rawley-Payne M, George S, Weiner L, Schatz D, Haller M, Clare-Salzler M,
Cook R, Mancini D, Abraham A, Hicks E, Cole G, Marks JB, Pugliese A, Matheson D,
Blaschke C, Arazo L, Cisneros M, Moran A, Wagner J, Nathan B, Boes MA, Becker D,
Toledo F, Riley K, Delallo K, Smith K, Raskin P, White P, Dickson B, Adhikari S,
Siegelman M, Alford M, Torres N, Harden T, Pruneda L, Cordova E, Wherrett D,
Eisel LA, Ahenkorah B, Razack N, Sriskandarajah M.
Affiliation(s): Author information:
(1)Divison of Adult Infectious Diseases, University of Colorado School of Medicine,
Aurora, USA.
Publication date & source: 2013, J Clin Virol. , 57(2):115-9
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.
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