A Cochrane review [Abstract] 1 included 70 studies with a total of 17 462 subjects. No differences in the hard-end points of patient and graft survival were demonstrated for or against TOR inhibitor (TORi; sirolimus and everolimus) in comparison with calcineurin inhibitors (CNI; ciclosporin or tacrolimus) and antimetabolites (azathioprine, mycophenolate) (table T1, T2). Need to change treatment and wound complications were higher with TOR-i, but there were less cytomegalovirus (CMV) infections (table T1, T2).
Outcomes (up to 2 years for primary outcomes) | Relative effect(95% CI) | Risk with CNI | Risk with TOR-I (95% CI) | No. of participants(studies)Certainty of the evidence |
---|---|---|---|---|
Death (all causes) | RR 1.31(0.87 to 1.98) | 25 per 1000 | 33 per 1000(22 to 50) | 3618 (19) Moderate |
Graft loss censored for death | RR 1.32(0.96 to 1.81) | 51 per 1000 | 68 per 1000(49 to 93) | 3277 (14) Moderate |
CMV infection | RR 0.43(0.29 to 0.63) | 157 per 1000 | 68 per 1000(46 to 99) | 2026 (13) High |
Adverse wound outcomes: all complications | RR 2.56(1.94 to 3.36) | 77 per 1000 | 198 per 1000(150 to 260) | 1679 (12) Moderate |
Number needing to change treatment | RR 2.42(1.88 to 3.11) | 132 per 1000 | 320 per 1000(249 to 412) | 3148 (14) Moderate |
Outcomes (up to 2 years for primary outcomes) | Relative effect(95% CI) | Risk with antimetabolites | Risk with TOR-I (95% CI) | No. of participants(studies)Certainty of the evidence |
---|---|---|---|---|
Death (all causes) | RR 1.06 (0.84 to 1.33) | 29 per 1000 | 31 per 1000(24 to 38) | 10 482 (31) Moderate |
Graft loss censored for death | RR 1.09(0.82 to 1.45) | 35 per 1000 | 38 per 1000(29 to 51) | 8 966 (26) Moderate |
CMV infection | RR 0.44(0.34 to 0.58) | 136 per 1000 | 59 per 1000(46 to 78) | 10 049 (26) Moderate |
Adverse wound outcomes: all complications | RR 1.56(1.28 to 1.90) | 155 per 1000 | 241 per 1000 (199 to 297) | 6 913 (17) Moderate |
Number needing to change treatment | RR 1.56 (1.28 to 1.90) | 174 per 1000 | 248 per 1000(203 to 302) | 9747 (25) Moderate |
A meta-analysis 2 included 28 RCTs with 6211 participants. There were less cytomegalovirus infections (RR 0.54, 95% CI 0.41 to 0.72; 19 trials, n=3914) and better creatinine clearance with mTORi compared with calcineurin inhibitor. There were no difference in graft loss (RR 1.10, 95% CI 0.74 to 1.65; 17 trials, n=3589), but more serious adverse events (RR 1.26, 95% CI 1.02 to 1.56; 7 trials, n=2173), proteinuria (RR 2.35, 95% CI 1.52 to 3.64; 12 trials, n=2844), and wound healing complications (RR 1.62, 95% CI 1.22 to 2.15; 7 trials, n=1826) with mTORi.
Comment: Data were limited beyond two years post-transplantation. The quality of evidence is downgraded by study quality (unclear allocation concealment in half of the studies).
Primary/Secondary Keywords