1. Accelerated Allograft Vasculopathy With Rituximab After Cardiac Transplantation
- Author
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Randall C. Starling, Brian Armstrong, Nancy D. Bridges, Howard Eisen, Michael M. Givertz, Abdallah G. Kfoury, Jon Kobashigawa, David Ikle, Yvonne Morrison, Sean Pinney, Josef Stehlik, Sudipta Tripathi, Mohamed H. Sayegh, Anil Chandraker, Barbara Gus, Karen Keslar, Bill Magyar, John Petrich, W. H. Wilson Tang, Kimberly Brooks, Michael Givertz, Charles Kelly, Katie Klein, Kerry Crisalli, Sandra DeBronkart, Joren Madsen, Marc Semigran, John Vetrano, Teresa DeMarco, Scott Fields, Carol Maguire, Robert Gordon, Allen Anderson, Jane Regalado, Anna Warzecha, Lee Goldberg, Caroline Olt, Kenneth Rockwell, Ashley Harris, Maryl Johnson, Susan Johnston, Chris Roginski, Rashid Ahmed, Ivy Cohen, Denise Peace, Tina Yao, Gloria Araujo, Arvind Bhimaraj, Eunice Karanga, Varsha Patel, Julie Chait, Mario Deng, Gregg Fonarow, Christina Shin, Charles Gibbs, Judson Hunt, Melissa Johnson, Tina Worley, Jeff Gibbs, John Kirk, Winter Redd, Julia Bryan, Anna French, A.G. Kfoury, Kristin Konery, Erika Feller, Myounghee Lee, Richard Pierson, Cindi Young, Theodora Hollifield, Kimberley Porter, Mariann Schulz, Adrian VanBakel, Kiran Khush, Helen Luikart, Son Nguyen, Michael Pham, David DeNofrio, Ryan O’Kelly, Lucilla Garcia, Sean Sana, Brandy Starks, Maria Thottam, Annie Yi, Barry Cabuay, Rachel Olson, Larry Tucker, Laura Uppgaard, Denise Lai, Colleen Poisker, Klaudija Dragicevic, Harrison Kelner, Darlette Luke, Jennifer Nelson, Ganesh Raveendran, Nick Kleissas, Srinivas Murali, Kenneth Rayl, Sarah Sherry, and Michele Cosgrove
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,030204 cardiovascular system & hematology ,Placebo ,Gastroenterology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Postoperative Complications ,Double-Blind Method ,hemic and lymphatic diseases ,Internal medicine ,Intravascular ultrasound ,medicine ,Humans ,Immunologic Factors ,030212 general & internal medicine ,Prospective Studies ,Vascular Diseases ,education ,CD20 ,education.field_of_study ,medicine.diagnostic_test ,biology ,business.industry ,Immunosuppression ,Middle Aged ,Allografts ,Transplantation ,Clinical trial ,biology.protein ,Heart Transplantation ,Rituximab ,Female ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Background 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. Objectives The study sought to determine whether B cell depletion therapy would attenuate the development of cardiac allograft vasculopathy. Methods 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. Results 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. Conclusions 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)
- Published
- 2018