Immunosuppression trends in solid organ transplantation: The future of individualization, monitoring, and management

Abstract

Immunosuppression regimens used in solid organ transplant have evolved significantly over the past 70 years in the United States. Early immunosuppression and targets for allograft success were measured by incidence and severity of allograft rejection and 1-year patient survival. The limited number of agents, infancy of human leukocyte antigen (HLA) matching techniques and lack of understanding of immunoreactivity limited the early development of effective regimens. The 1980s and 1990s saw incredible advancements in these areas, with acute rejection rates halving in a short span of time. However, the constant struggle to achieve the optimal balance between under- and overimmunosuppression is weaved throughout the history of transplant immunosuppression. The aim of this paper is to discuss the different eras of immunosuppression and highlight the important milestones that were achieved while also discussing this in the context of rational agent selection and regimen design. This discussion sets the stage for how we can achieve optimal long-term outcomes during the next era of immunosuppression, which will move from universal protocols to patient-specific optimization.

Keywords: immunosuppression; solid.

FIGURE 1

Maintenance (top panel) and induction (bottom panel) immunosuppression utilization in US Kidney Transplant Recipients 1995 to 2004.^,– AZA, azathioprine; Bas, basiliximab; CyA, cyclosporine; hATG, horse antilymphocyte globulin; hATG, horse antithymocyte globulin; MMF, mycophenolate; rATG, rabbit antilymphocyte globulin; rATG, rabbit antithymocyte globulin; Sir, sirolimus; Tac, tacrolimus

FIGURE 2

One-year acute rejection rates in kidney transplant recipients from 1993 to 2010 demonstrated a 3-phase trend

FIGURE 3

Solid organ transplant. A brief selected history lesson of significant events based on review of the literature, which outline major regulatory and immunosuppression milestones that have impacted outcomes. This figure does not include the major milestones of organ preservation or associated technology or the extensive advances related to infection over the past decades. Regulatory milestones can be accessed through www.cmc.gov/ (accessed June 9, 2020); https://www.organdonor.gov/about/facts-terms/history.html (accessed August 4, 2020). CMS, Centers for Medicare and Medicaid Services; FDA, US Food and Drug Administration; HOPE, Heart Outcomes Prevention Evaluation; mTOR, mammalian target of rapamycin

FIGURE 4

Scientific Registry of Transplant Recipients (SRTR) reported current induction trends adapted from 2018 Annual Data Report. Scientific Registry of Transplant Recipients http://srtr.transplant.hrsa.gov/annual_reports/Default.aspx (accessed June 3, 2020)