Abatacept as rescue immunosuppression after calcineurin inhibitor treatment failure in renal transplantation

Am J Transplant. 2019 Aug;19(8):2342-2349. doi: 10.1111/ajt.15319. Epub 2019 Mar 12.

Abstract

A majority of kidney transplant recipients receive calcineurin inhibitor-based immunosuppression. However, some do not tolerate calcineurin inhibitors and require other immunosuppressive strategies. Until recently, alternative approaches have been associated with inferior outcomes, but recent methods have effectively utilized belatacept in calcineurin inhibitor-intolerant patients. Though promising, belatacept uptake has been limited by higher acute rejection rates, unavailability due to production shortages, and logistical challenges as a result of intravenous infusion requirements. Interestingly, its predecessor abatacept is clinically available in subcutaneous formulation to treat autoimmune disorders but has not been used in clinical transplantation. Here we report on a series of 9 calcineurin inhibitor-intolerant transplant recipients converted to abatacept early after transplant as rescue immunosuppression during periods of belatacept unavailability. Retrospective review revealed successful allograft salvage and 100% patient and graft survival (median 115 months) after conversion to abatacept. Patients received abatacept for a median duration of 82 months with stable, long-term renal allograft function, a single cellular rejection episode, and no clinically apparent protective immunity concerns. Hence our findings suggest that future clinical studies utilizing abatacept either de novo or as conversion therapy in transplant recipients should be considered.

Keywords: clinical research/practice; costimulation; immunosuppressant - calcineurin inhibitor: tacrolimus; immunosuppressant - fusion proteins and monoclonal antibodies: costimulation molecule specific; immunosuppression/immune modulation; immunosuppressive regimens - rescue; kidney (allograft) function/dysfunction; kidney transplantation/nephrology.

MeSH terms

  • Abatacept / therapeutic use*
  • Adult
  • Calcineurin Inhibitors / adverse effects*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / drug therapy*
  • Graft Rejection / etiology
  • Graft Rejection / pathology
  • Graft Survival / drug effects*
  • Graft Survival / immunology
  • Humans
  • Immune Tolerance / drug effects
  • Immune Tolerance / immunology*
  • Immunosuppression Therapy
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Risk Factors

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Abatacept