Wound healing adverse events in kidney transplant recipients receiving everolimus with reduced calcineurin inhibitor exposure or current standard-of-care: insights from the 24-month TRANSFORM study

Expert Opin Drug Saf. 2020 Oct;19(10):1339-1348. doi: 10.1080/14740338.2020.1792441. Epub 2020 Jul 20.

Abstract

Objectives: In TRANSFORM, de novo kidney transplant recipients received either everolimus in combination with reduced-exposure calcineurin inhibitor (EVR+rCNI) at standard EVR pre-dose concentrations of 3-8 ng/mL or mycophenolic acid plus standard-exposure CNI (MPA+sCNI). The authors analyzed the incidence of wound healing adverse events (WHAEs) over the 2-year study period 15.

Methods: Patients were randomized to either EVR+rCNI or MPA+sCNI, both combined with induction therapy and steroids 19.

Results: The safety population consisted of 2,026 patients (EVR+rCNI: 1,014, MPA+sCNI: 1,012). The proportion of patients with at least 1 WHAE was comparable between EVR+rCNI and MPA+sCNI treatment groups [20.6% vs. 17.3%; risk ratio (RR): 1.19; 95% confidence interval (CI): 0.99, 1.43] at month 24. The numerical difference between EVR+rCNI and MPA+sCNI was mainly caused by an increased proportion of EVR patients with lymphocele and wound dehiscence [7.5% vs. 5.1% (RR: 1.46; 95% CI: 1.04, 2.05) and 3.9% vs. 1.8% (RR: 2.22; 95%CI: 1.28, 3.84), respectively] 20.

Conclusion: The immediate introduction of EVR+rCNI after kidney transplantation was associated with an overall comparable incidence of WHAEs versus current standard-of-care over the 24-month study period. There was an increased relative risk of experiencing lymphocele and wound dehiscence but the absolute risks were rather low in both groups 21.

Ct.gov identifier: NCT01950819.

Keywords: Calcineurin inhibitor; everolimus; kidney transplantation; randomized; safety; wound healing.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Calcineurin Inhibitors / administration & dosage
  • Calcineurin Inhibitors / adverse effects*
  • Everolimus / administration & dosage
  • Everolimus / adverse effects*
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Incidence
  • Kidney Transplantation
  • Lymphocele / epidemiology
  • Lymphocele / etiology
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / adverse effects
  • Risk
  • Surgical Wound Dehiscence / epidemiology
  • Surgical Wound Dehiscence / etiology
  • Wound Healing / drug effects*

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Everolimus
  • Mycophenolic Acid

Associated data

  • ClinicalTrials.gov/NCT01950819