Comment: The quality of evidence is downgraded by study limitations (unclear allocation concealment, unclear blinding of outcome assessment, incomplete outcome data and mostly commercially funded studies).
A Cochrane review [Abstract] 1 included 23 studies with a total of 3 301 subjects comparing mycophenolate mofetil (MMF, a mycophenolic acid) with azathioprine (AZA). MMF treatment reduced the risk for graft loss including death and for death-censored graft loss, and the risk for any acute rejection, biopsy-proven acute rejection and antibody-treated acute rejection T1. No statistically significant difference for MMF versus AZA treatment was found for all-cause mortality. Pooled analyses failed to show a significant and meaningful difference between MMF and AZA in kidney function measures.Data on malignancies and infections were sparse, except for cytomegalovirus (CMV) infections. Adverse event profiles varied: gastrointestinal symptoms were more likely in MMF treated patients and thrombocytopenia and elevated liver enzymes were more common in AZA treatment.
| Outcome | Relative effect(95% CI) | Assumed risk - control=AZA | Corresponding risk - intervention=MMF | Number of participants (studies) |
|---|---|---|---|---|
| Death, all causeFollow-up: 0.5 to 5 years | RR 0.95 (0.7 to 1.29) | 49/1000 | 47/1000(34 to 63) | 2987 (16) |
| Graft loss, censored for deathFollow-up: 0.5 to 6 years | RR 0.78 (0.61 to 0.98) | 11/100 | 9/100(7 to 11) | 2540 (17) |
| Acute rejection, totalFollow-up: 0.5 to 5 years | RR 0.65 (0.57 to 0.73) | 35/100 | 23/100(20 to 26) | 3301 (22) |
| Infection, CMV tissue invasive Follow-up: 0.5 to 3 years | RR 1.7 (1.1 to 2.61) | 4/100 | 7/100(5 to 11) | 1510 (7) |
Another Cochrane review [Abstract] 2 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 T2). Need to change treatment and wound complications were higher with TOR-i, but there were less cytomegalovirus (CMV) infections (table T2).
| 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 |
Date of latest search: 2020-01-10
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