Comparison in Patients' Adherence, Adverse Effects, and Clinical Outcomes Among Liver Transplant Recipients Using Immediate-Release Tacrolimus (Prograf®) Versus Extended-Release Tacrolimus (Advagraf®): First Report from Iran.

INTRODUCTION

Medication adherence is a crucial factor in liver transplant patients' improvement of quality of life and survival rates and reduction of allograft rejection. Tacrolimus plays a pivotal role in post-transplant immunosuppressive therapy, which is available both as twice-daily immediate-release tacrolimus (Prograf®) and once-daily extended-release tacrolimus (Advagraf®). This study compared adherence, adverse effects, and clinical outcomes between patients using once-daily extended-release tacrolimus (ERT; Advagraf®) and twice-daily immediate-release tacrolimus (IRT; Prograf®) in a real-world setting.

METHODS

This prospective observational study involved eligible adult liver transplant recipients at least six months post-transplant, prescribed either Prograf® or Advagraf® as part of their immunosuppressive regimen. The primary outcome was the change in adherence from baseline to six months. Patient adherence was assessed using the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS) at baseline and 6 months. The dose-to-concentration ratio of tacrolimus, potential side effects, and intra-patient variability were assessed at baseline and at one-month and six-month follow-ups. Data were collected through face-to-face interviews, medical records review, pharmacy database exploration, and phone surveys.

RESULTS

Baseline adherence was similar between the groups (Prograf® 48.5% vs. Advagraf® 41.2%, P=0.39). At six months, the ERT (Advagraf®) group was associated with higher adherence rates in adjusted analysis (Adjusted Odds Ratio [AOR]: 2.5, 95% CI: 1.1-5.8). Factors significantly associated with higher adherence included older age (AOR: 1.05 per year, 95% CI: 1.01-1.09) and shorter time since transplant (AOR: 0.98 per month, 95% CI: 0.97-0.99). The ERT group also reported a lower incidence of hand tremors (15% vs. 32%, P=0.015). Trough levels, dose/concentration ratios, and renal function were comparable.

CONCLUSION

In this observational study, the once-daily Advagraf® formulation was associated with significantly better medication adherence and a lower reported incidence of tremors compared to twice-daily Prograf®. These findings should be interpreted in the context of the study's non-randomized design and potential confounding.