Challenges of calcineurin inhibitor withdrawal following combined pancreas and kidney transplantation: Results of a prospective, randomized clinical trial

Peter G. Stock, Roslyn B. Mannon, Brian Armstrong, Natasha Watson, David Ikle, Mark A. Robien, Yvonne Morrison, Jon Odorico, Jonathan Fridell, Aneesh K. Mehta, Kenneth A. Newell

Research output: Contribution to journalArticle

Abstract

In a phase 2 multicenter open-label randomized trial sponsored by the National Institutes of Health, simultaneous pancreas-kidney (SPK) recipients were randomized to a calcineurin inhibitor (CNI)–based immunosuppressive regimen (tacrolimus) (n = 21), or an investigational arm using low-dose CNI plus costimulation blockade (belatacept) with intended CNI withdrawal (n = 22). Both arms included induction therapy with rabbit ATG, mycophenolate sodium, or mycophenolate mofetil and rapid withdrawal of steroids. Enrollment and CNI withdrawal were stopped after 43/60 planned subjects had been enrolled. At that time, the rate of biopsy-proven acute rejection (BPAR) of the pancreas was low in both groups until CNI was withdrawn, with four of the five pancreas rejections occurring during or after CNI withdrawal. The rate of BPAR of kidney allografts was low in both control (9.5%) and investigational (9.1%) arms. Pancreas graft survival at 52 weeks, defined by insulin independence, was 21 (100%) in the control group and 19 (86%) in the investigational arm. One subject in the investigational arm died with functioning pancreas and kidney grafts. Renal function at week 52 was similar in both arms. Costimulation blockade with belatacept did not provide sufficient immunosuppression to reliably prevent pancreas rejection in SPK transplants undergoing CNI withdrawal.

Original languageEnglish (US)
Pages (from-to)1668-1678
Number of pages11
JournalAmerican Journal of Transplantation
Volume20
Issue number6
DOIs
StatePublished - Jun 1 2020

Keywords

  • clinical research/practice
  • costimulation
  • diabetes: type 1
  • immunosuppressant—calcineurin inhibitor: tacrolimus
  • immunosuppression/immune modulation
  • pancreas/simultaneous pancreas-kidney transplantation
  • rejection: acute
  • sensitization

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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  • Cite this

    Stock, P. G., Mannon, R. B., Armstrong, B., Watson, N., Ikle, D., Robien, M. A., Morrison, Y., Odorico, J., Fridell, J., Mehta, A. K., & Newell, K. A. (2020). Challenges of calcineurin inhibitor withdrawal following combined pancreas and kidney transplantation: Results of a prospective, randomized clinical trial. American Journal of Transplantation, 20(6), 1668-1678. https://doi.org/10.1111/ajt.15817