Conversion from twice-daily everolimus to once-daily sirolimus in long-term stable liver transplant recipients

Transpl Immunol. 2024 Apr:83:102014. doi: 10.1016/j.trim.2024.102014. Epub 2024 Feb 21.

Abstract

Background: After organ transplantation, strategies for simplifying the therapeutic regimen may improve adherence and prevent acute organ rejection and/or late graft loss. The present study aimed to evaluate the safety and efficacy of conversion from everolimus (EVR) twice daily to sirolimus (SIR) once daily in a large cohort of liver transplantation (LT) patients.

Methods: We included 108 LT patients with at least 12 months of post-transplant follow-up and no rejection episodes in the last year. Conversion was based on a 1:1 ratio (but eventually adapted to available formulations of SIR).

Results: The median age at the time of conversion was 68.9 years (range: 26.1-83.6); 75.0% were men. The main indications for mTOR inhibitor use were renal failure (38.9%) and/or a history of malignancy (37.0%). Median conversion time after LT was 14.8 years (range: 2.3-31.5). The median dose of EVR and SIR (initially) was 1.50 mg/day (range: 0.5-4.5). The mean follow-up after conversion was 15.8±4.4 months. Median serum EVR/SIR trough levels before/after conversion were 3.85 ng/mL vs. 6.32 ng/mL (p < 0.05), i.e. a 1:1.64 ratio. At the end of follow-up after conversion, the median dose of SIR was 1.25 mg/day (range: 0.5-3.5), and the mean serum SIR trough level was 5.23 ng/mL; 9 patients (8.3%) had returned to EVR, because of side effects (mainly digestive), that resolved thereafter. No biopsy-proven acute rejection episode was observed. Finally, 87.1% of patients considered the conversion beneficial and the cost was reduced by 50.3%.

Conclusion: The results of our study indicate that conversion from once-daily EVR to once-daily SIR in stable LT patients is safe, but needs dose adaptations and careful monitoring.

Keywords: Conversion; Cost; Everolimus; Liver transplantation; Quality of life; Sirolimus; mTOR inhibitors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Everolimus
  • Female
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Liver Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Organ Transplantation*
  • Sirolimus
  • Tacrolimus / adverse effects
  • Transplant Recipients

Substances

  • Everolimus
  • Sirolimus
  • Immunosuppressive Agents
  • Tacrolimus