Is Mycophenolate Mofetil Really Necessary in Renal Transplantation?
Is Mycophenolate Mofetil Really Necessary in Renal Transplantation?
Background: The Mycophenolate Steroids Sparing (MYSS) study showed that, when combined with ciclosporin microemulsion, mycophenolate mofetil is not superior to azathioprine in preventing acute rejection after renal transplantation. Mycophenolate is, however, more expensive than azathioprine.
Objective: To compare long-term outcomes with azathioprine and mycophenolate in renal transplant recipients receiving ciclosporin microemulsion.
Design: The MYSS follow-up study was the continuation of a multicenter, European, prospective, randomized, parallel-group trial that enrolled recipients of a first kidney transplant from a deceased donor between October 1997 and May 2001.
Intervention: Participants in the original trial were randomized on a 1:1 basis to receive mycophenolate 1 g twice-daily or azathioprine 100150 mg/day, in addition to ciclosporin microemulsion and steroids. Steroids were gradually withdrawn in suitable patients and follow-up continued for up to 21 months after transplantation. Patients who entered the extension study were assessed every 6 months until October 2004.
Outcome measures: The primary outcome of the follow-up study was glomerular filtration rate (GFR) 5 years after transplantation, as estimated using the Walser equation. Decline in GFR between month 6 after transplantation and study end, patient and graft survival, and the incidences of new-onset proteinuria (urine protein excretion >0.5 g/24 h on 2 consecutive measurements), acute rejection and adverse events were secondary outcomes.
Results: Of the 334 patients who received treatment in the MYSS study, 248 entered the follow-up study (124 in each treatment arm). The azathioprine group had a higher proportion of females than did the mycophenolate group (41.1% vs 26.6%; P = 0.02); other recipient and donor characteristics were comparable. Median follow-up was 65.5 months in the patients who received azathioprine and 64.1 months in those who received mycophenolate. At 5 years after transplantation, there was a trend toward higher GFR in the azathioprine group than in the mycophenolate group (mean difference 4.67 ml/min; 95% CI -0.43 to 9.77 ml/min; P = 0.07; n = 149). At 6 years after transplantation, graft survival was 93.2% in the azathioprine patients and 93.9% in the mycophenolate patients (P = 0.83); patient survival was 96% in both groups. The azathioprine group did not differ significantly from the mycophenolate group in the rate of GFR decline (-1.10 ml/min/1.73 m/year vs -1.23 ml/min/1.73 m/year; P = 0.83), or the incidences of new-onset proteinuria (25.0% vs 27.4%; P = 0.67), acute rejection (52.4% vs 46.0%; P = 0.31) or adverse events. When patients who did and did not complete steroid withdrawal were analyzed separately, the comparisons between azathioprine and mycophenolate yielded similar results.
Conclusion: Azathioprine and mycophenolate seem to provide comparable long-term outcomes in renal transplant patients receiving ciclosporin microemulsion.
Synopsis
Background: The Mycophenolate Steroids Sparing (MYSS) study showed that, when combined with ciclosporin microemulsion, mycophenolate mofetil is not superior to azathioprine in preventing acute rejection after renal transplantation. Mycophenolate is, however, more expensive than azathioprine.
Objective: To compare long-term outcomes with azathioprine and mycophenolate in renal transplant recipients receiving ciclosporin microemulsion.
Design: The MYSS follow-up study was the continuation of a multicenter, European, prospective, randomized, parallel-group trial that enrolled recipients of a first kidney transplant from a deceased donor between October 1997 and May 2001.
Intervention: Participants in the original trial were randomized on a 1:1 basis to receive mycophenolate 1 g twice-daily or azathioprine 100150 mg/day, in addition to ciclosporin microemulsion and steroids. Steroids were gradually withdrawn in suitable patients and follow-up continued for up to 21 months after transplantation. Patients who entered the extension study were assessed every 6 months until October 2004.
Outcome measures: The primary outcome of the follow-up study was glomerular filtration rate (GFR) 5 years after transplantation, as estimated using the Walser equation. Decline in GFR between month 6 after transplantation and study end, patient and graft survival, and the incidences of new-onset proteinuria (urine protein excretion >0.5 g/24 h on 2 consecutive measurements), acute rejection and adverse events were secondary outcomes.
Results: Of the 334 patients who received treatment in the MYSS study, 248 entered the follow-up study (124 in each treatment arm). The azathioprine group had a higher proportion of females than did the mycophenolate group (41.1% vs 26.6%; P = 0.02); other recipient and donor characteristics were comparable. Median follow-up was 65.5 months in the patients who received azathioprine and 64.1 months in those who received mycophenolate. At 5 years after transplantation, there was a trend toward higher GFR in the azathioprine group than in the mycophenolate group (mean difference 4.67 ml/min; 95% CI -0.43 to 9.77 ml/min; P = 0.07; n = 149). At 6 years after transplantation, graft survival was 93.2% in the azathioprine patients and 93.9% in the mycophenolate patients (P = 0.83); patient survival was 96% in both groups. The azathioprine group did not differ significantly from the mycophenolate group in the rate of GFR decline (-1.10 ml/min/1.73 m/year vs -1.23 ml/min/1.73 m/year; P = 0.83), or the incidences of new-onset proteinuria (25.0% vs 27.4%; P = 0.67), acute rejection (52.4% vs 46.0%; P = 0.31) or adverse events. When patients who did and did not complete steroid withdrawal were analyzed separately, the comparisons between azathioprine and mycophenolate yielded similar results.
Conclusion: Azathioprine and mycophenolate seem to provide comparable long-term outcomes in renal transplant patients receiving ciclosporin microemulsion.
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