Portal de Periódicos da CAPES

Accelerated Allograft Vasculopathy With Rituximab After Cardiac Transplantation

2019; Elsevier BV; Volume: 74; Issue: 1 Linguagem: Inglês

10.1016/j.jacc.2019.04.056

1558-3597

Randall C. Starling, Brian Armstrong, Nancy D. Bridges, Howard J. Eisen, Michael M. Givertz, Abdallah G. Kfoury, Jon Kobashigawa, David Iklé, Yvonne Morrison, Sean Pinney, Josef Stehlik, Sudipta Tripathi, Mohamed H. Sayegh, Anil Chandraker, Barbara Gus, Karen S. Keslar, Boglárka Magyar, John Petrich, Randall C. Starling, W.H. Wilson Tang, Kimberly Brooks, Michael M. Givertz, Charles M. Kelly, Katie Klein, Kerry Crisalli, Sandra de-Bronkart, Joren C. Madsen, Marc J. Semigran, J.S. Vetrano, Teresa DeMarco, Scott Fields, Carol Maguire, Robert D. Gordon, Allen S. Anderson, Jane Regalado, Anna Warzecha, Lee R. Goldberg, Caroline Olt, Kenneth Rockwell, Ashley D. Harris, Maryl R. Johnson, Susan Johnston, Chris Roginski, Rashid Ahmed, Ivy Cohen, Denise Peace, Sean Pinney, Tina Yao, Gloria Araujo, Arvind Bhimaraj, Eunice Karanga, Varsha Patel, J. Chait, Mario C. Deng, Gregg C. Fonarow, Christina Shin, Charles E. Gibbs, Judson Hunt, Melissa M. Johnson, Tina Worley, Jeff Gibbs, John Kirk, Winter Redd, Josef Stehlik, Julia Bryan, Anna French, A.G. Kfoury, Kristin Konery, Erika Feller, Myoung-Hee Lee, Richard N. Pierson, Cindi A. Young, Theodora Hollifield, Kimberley Porter, Mariann Schulz, Adrian B VanBakel, Kiran K. Khush, Helen Luikart, Son Nguyen, Michael Pham, David DeNofrio, Ryan O’Kelly, Lucilla Garcia, Jon Kobashigawa, S. Sana, Brandy Starks, Maria Thottam, Annie Yi, B. Cabuay, Rachel Olson, Larry A. Tucker, Laura Uppgaard, Howard J. Eisen, Denise Lai, Colleen Poisker, Klaudija Dragicevic, Harrison Kelner, Darlette Luke, Jennifer Nelson, Ganesh Raveendran, Nick Kleissas, Srinivas Murali, Kenneth R. Rayl, Sarah Sherry, Michele Cosgrove,

Viral Infections and Immunology Research

The CTOT-11 (Prevention of Cardiac Allograft Vasculopathy Using Rituximab Therapy in Cardiac Transplantation [Clinical Trials in Organ Transplantation-11]) study was a randomized, placebo-controlled, multicenter, double-blinded clinical trial in nonsensitized primary heart transplant (HTX) recipients. The study sought to determine whether B cell depletion therapy would attenuate the development of cardiac allograft vasculopathy. A total of 163 HTX recipients were randomized to rituximab 1,000 mg intravenous or placebo on days 0 and 12 post-transplant. Primary outcome was change in percent atheroma volume (PAV) from baseline to 1 year measured by intravascular ultrasound. Secondary outcomes included treated episodes of acute rejection, de novo anti-HLA antibodies (including donor-specific antibodies), and phenotypic differentiation of B cells. There were no significant differences at study entry between the rituximab and placebo groups. Paired intravascular ultrasound measures were available at baseline and 1 year in 86 subjects (49 rituximab, 37 placebo). The mean ± SD change in PAV at 12 months was +6.8 ± 8.2% rituximab versus +1.9 ± 4.4% placebo (p = 0.0019). Mortality at 12 months was 3.4% rituximab versus 6.8% placebo (p = 0.47); there were no retransplants or post-transplant lymphoproliferative disorder. The rate of treated rejection was 24.7% rituximab versus 32.4% placebo (p = 0.28). Rituximab therapy effectively eliminated CD20+/CD19+ B cells followed by a gradual expansion of a CD19– cell population in the rituximab-treated group. A marked, unexpected increase in coronary artery PAV with rituximab was observed during the first year in HTX recipients. One-year mortality was not impacted; however, longer-term follow-up and mechanistic explanations are required. (Prevention of Cardiac Allograft Vasculopathy Using Rituximab [Rituxan] Therapy in Cardiac Transplantation; NCT01278745)