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ILTS 2014: DIAMOND study updates: Posters by Prof W Bechstein and Prof G Tisone
DIAMOND: preserving renal function (RF) with tac prolonged-release in de novo LTx pts with different primary disease (PD). Wolf Bechstein et al, Goethe University Hospital and Clinics Frankfurt, Germany.
DIAMOND: preserving renal function (RF) over 24 wks with prolonged-release tac in de novo LTx pts by baseline (BL) eGFR/MELD. Giuseppe Tisone et al, Policlinico di Tor Vergata, Rome, Italy.
An immunosuppressive regimen consisting of low dose once-daily prolonged-release tacrolimus results in better renal function and a significantly lower risk of acute rejection after liver transplantation that starting on a standard dose of once-daily tacrolimus, irrespective of either the primary disease indication for the transplantation or renal function at baseline. Results of subgroup analyses from the Advagraf Studied In Combination with Mycophenolate Mofetil and Basiliximab in Liver Transplantation (DIAMOND) study were presented as posters at the ILTS 2014 congress.
The DIAMOND study was a 24-week randomised trial carried out at 72 centres in Europe, North and South America, Russia and South Africa with the aim of determining the effects on renal function of different dosing regimens of once-daily prolonged-release tacrolimus after de novo liver transplantation. Eligible patients were randomised to either standard-dose once-daily tacrolimus (Arm 1; n=283), low-dose once-daily tacrolimus plus basiliximab (Arm 2; n=287), or standard-dose once-daily tacrolimus from Day 5 post-transplant plus basiliximab (Arm 3; n=274). The primary endpoint was renal function as assessed by the estimated glomerular filtration rate (eGFR) at Week 24.
The primary analysis showed that patients in Arms 2 and 3 had significantly higher eGFR rates at Week 24 compared with Arm 1 (76.4 and 73.3 versus 67.4mL/min/1.73m2; p<0.001 and p<0.047, respectively). Renal function was preserved in all treatment arms, and no significant differences were noted between the treatment arms with respect to graft or patient survival. A subgroup analysis of renal function by primary disease indication at baseline showed that in patients with hepatocellular carcinoma, the mean change in renal function was significantly less in Arms 2 and 3 compared with Arm 1 (p=0.009 and 0.003, respectively). In patients with alcoholic liver disease (ALD), hepatitis C viral infection (HCV) or other primary disease indication the mean change in renal function was numerically less in Arms 2 and 3 compared with Arm 1, although this difference did not reach statistical significance (Table 1).
A further subgroup analysis in the DIAMOND dataset addressed the effect of renal (eGFR) and liver (MELD score) function on renal function at Week 24, and found that in patients with a baseline eGFR of >60 mL/min/1.73m2, the mean change in renal function was significantly less in Arm 2 compared with Arm 1 (p=0.023). In patients with a baseline eGFR of <60 mL/min/1.73m2, the mean change in renal function was significantly less in Arms 2 and 3 compared with Arm 1 (p=0.013 and 0.005, respectively) (Table 2). In contrast, the effect of liver function was significant only in patients with a MELD score of <25 at baseline, for whom the mean change in renal function from baseline to Week 24 was significantly less in Arms 2 and 3 compared with Arm 1 (p=0.009 and 0.048, respectively). In patients with higher MELD score at baseline there was a numeric smaller change in renal function in Arms 2 and 3 compared with Arm 1, but this difference did not reach statistical significance. The DIAMOND investigators concluded that a regimen of low dose prolonged-release, once-daily tacrolimus confers a significant renal function advantage at Week 24, regardless of primary disease indication and renal or liver function at baseline.
Table 1. Renal function (eGFR) by primary disease indication at baseline.
|
|
Arm |
ALD mL/min/1.73m2 (SD)/n |
HCC mL/min/1.73m2 (SD)/n |
HCV mL/min/1.73m2 (SD)/n |
Other mL/min/1.73m2 (SD)/n |
|
Baseline (BL) |
1 |
82.4 (38.8)/58 |
101.2 (38.2)/87 |
81.5 (25.0)/46 |
91.9 (42.0)/86 |
|
|
2 |
81.1 (40.8)/80 |
92.1 (33.0)/79 |
86.9 (37.9)/47 |
97.6 (47.5)/77 |
|
|
3 |
82.1 (35.2)/60 |
93.0 (29.3)/81 |
84.4 (32.7)/37 |
94.3 (38.4)/91 |
|
Week 24 |
1 |
59.3 (32.5)/58 |
58.7 (32.8)/87 |
58.2 (25.9)/46 |
63.9 (37.1)/86 |
|
|
2 |
66.2 (28.4)/80 |
64.8 (35.6)/79 |
67.8 (43.9)/47 |
77.3 (42.1)/77 |
|
|
3 |
63.2 (29.8)/60 |
67.6 (26.9)/81 |
61.5 (36.8)/37 |
68.5 (36.9)/91 |
|
Change from BL |
1 |
–23.1 (38.1) |
–42.6 (42.3) |
–23.4 (29.5) |
–28.0 (38.2) |
|
|
2 |
–14.9 (42.5) |
–27.2 (38.2) |
–19.1 (45.4) |
–20.3 (48.3) |
|
|
3 |
–18.8 (42.9) |
–25.4 (29.9) |
–22.9 (46.9) |
–25.9 (43.9) |
|
P value (change from BL) |
Arm 1 vs 2 |
0.2503 |
0.0088 |
0.6166 |
0.2625 |
|
|
Arm 1 vs 3 |
0.5710 |
0.0031 |
0.9586 |
0.7463 |
|
|
Arm 2 vs 3 |
0.5814 |
0.7485 |
0.6742 |
0.4112 |
Pts with missing data were excluded
Table 2. Renal function at Week 24 by renal function at baseline
|
|
eGFR≥60mL/min/1.73m2 |
|
|
eGFR<60mL/min/1.73m2 |
|
|
|
|
Arm 1 (n=222) |
Arm 2 (n=221) |
Arm 3 (n=219) |
Arm 1 (n=56) |
Arm 2 (n=62) |
Arm 3 (n=50) |
|
BL, mean (SD) |
103.9 (31.6) |
104.6 (31.6) |
101.2 (26.7) |
41.2 (15.7) |
36.3 (18.2) |
40.0 (15.7) |
|
Wk 24, mean (SD) |
65.8 (31.6) |
74.9 (36.1) |
68.6 (33.4) |
39.0 (29.9) |
48.5 (34.6) |
55.1 (25.9) |
|
Change from BL, mean (SD) |
–38.1 (37.8) |
–29.7 (41.7) |
–32.6 (36.9) |
–2.2 (29.0) |
12.1 (33.3) |
15.1 (30.6) |
|
P value (change from BL) |
Arm 1 vs 2 |
Arm 1 vs 3 |
Arm 2 vs 3 |
Arm 1 vs 2 |
Arm 1 vs 3 |
Arm 2 vs 3 |
|
|
0.0231 |
0.1372 |
0.4340 |
0.0133 |
0.0049 |
0.6227 |
Pts with missing data were excluded
