Published online Mar 27, 2021. doi: 10.4254/wjh.v13.i3.375
Peer-review started: November 5, 2020
First decision: November 30, 2020
Revised: January 4, 2021
Accepted: February 18, 2021
Article in press: February 18, 2021
Published online: March 27, 2021
Processing time: 134 Days and 13.6 Hours
Tacrolimus, a calcineurin inhibitor is an important immunosuppressive medication post liver transplantation. Compliance to immunosuppression is important and non-adherence can lead to rejection and graft loss. To maintain good adherence, less frequently administering regimen were proved to be effective.
Recently, tacrolimus once-daily prolonged-release (PR) formulation was developed. Several studies have shown evidence that conversion from the twice-daily, immediate release to PR tacrolimus was well tolerated, safe and conveniently used in stable patients after liver transplantation.
Our objective was to conduct a metanalysis and systematic review of the published clinical trials that studied the safety and efficacy of PR tacrolimus compared to immediate release tacrolimus.
MEDLINE, EMBASE, CENTRAL databases were searched for clinical trials until December 2020. Efficacy outcome measured as the rate of treatment failure indicated by biopsy-proven acute rejection, Serum creatinine, graft loss, or death. Two reviewers independently selected studies, collected data and assessed risk of bias. The results are reported as risk ratio with 95%CI for dichotomous data.
Seven studies included with 965 patients. All the included studies were of moderate quality according to the risk of bias assessment using Cochrane Risk of Bias tool. Biopsy-proven acute rejection was reported in four studies, and pooled analysis of those studies indicated similar rejections in both twice daily and once daily tacrolimus groups. We also found no significant difference between both groups for renal outcome (serum creatinine; mean difference, 0.001 mg/dL, 95%CI: -0.042 to 0.043, n = 846, I2 = 18.6%). Similarly, there was similar number of adverse events such as hypertension, headache, back pain, blood related disorders, infections and nausea observed in both groups.
The analysis findings confirm that both once daily and twice daily tacrolimus formulations are comparable in terms of efficacy and safety outcomes.
Long-term follow-up randomized controlled trials with large sample sizes are required. Also, to assess acceptability by patients, quality of life and economic evaluations should be conducted.