Table 1.
Summary of randomized controlled trials evaluating belatacept in kidney transplant recipients.
| Comparator | Intervention | Nb. of patients | Setting | Follow–up | Death | Graft failure | Death or graft failure | Rejections | CV events | Infections | Cancers | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Belatacept vs. CNI, for de novo KT recipients | ||||||||||||
| Vincenti et al. (9) | CsA (C0: 150–300 mg/l until M1, then 100–250) | First randomization: LI: 10 mg/kg, 6 inj./3 months MI: 10 mg/kg, 11 inj./6 months Second randomization: 4w: 5 mg/kg every 4w 8w: 5 mg/kg every 8w |
(Total nb: 218) CsA: 73 LI: 71 MI: 74 CsA:71 4w: 62 8w: 60 | Basiliximab for induction, steroids + MYC for maintenance | 10 years | (Total nb: 15) CsA: 5/73 LI: 2/71 MI: 8/74 |
(Total nb: 8) CsA: 3/73 LI: 1/71 MI: 4/71 | LI vs. CsA: HR 0.95 [0.38–2.36] MI vs. CsA: HR 0.24 [0.24–0.91] 4w vs. CsA: HR 0.55 [0.17–1.73] 8w vs. CsA: HR 0.52 [0.16–1.74] |
LI vs. CsA: HR 1.61 [0.85–3.05] MI vs. CsA: HR 0.95 [0.47–1.92] 4w vs. CsA: HR 1.06 [0.35–3.17] 8w vs. CsA: HR 2.00 [0.75–5.35] | (Death from CV cause) CsA: 2/73 LI: 1/71 MI: 1/71 |
(Serious events) CsA: 15.0/100py LI: 6.7/100py MI: 10.4/100py CsA: 16.7/100py 4w: 6.0/100py 8w: 10.4/100py | CsA: 3.0/100py LI: 2.5/100py MI: 10.4/100py CsA: 3.3/100py 4w: 2.8/100py 8w: 3.3/100py |
| Vincenti et al. (10) BENEFIT |
CsA (C0: 150–300 mg/l until M1, then 100–250) | Bela LI then 4w Bela MI then 4w |
(Total nb: 666) CsA: 221 LI: 226 MI: 219 | SCD Basiliximab for induction, steroids + MYC for maintenance |
7 years | (Total nb: 58) LI vs. CsA: HR 0.55 [0.30–1.04] MI vs. CsA: HR 0.62 [0.33–1.14] |
(Total nb: 38) LI vs. CsA: 0.59 [0.28–1.25] MI vs. CsA: 0.56 [0.25–1.21] |
LI vs. CsA:
HR 0.57 [0.35–0.94] MI vs. CsA: HR 0.57 [0.35–0.95] |
CsA: 11.4% LI: 18.3% MI: 24.4% | (Death from CV cause) CsA: 11/221 LI: 6/226 MI: 6/219 (Serious cardiac+vascular events) CsA: 2.0+1.8/100py LI: 1.4+1.5/100py MI: 2.2+2.9/100py |
(Serious events) CsA: 13.3/100py LI: 10.7/100py MI: 10.6/100py | CsA: 2.6/100py LI: 1.8/100py MI: 2.1/100py |
| Durrbach et al. (11) BENEFIT–EXT |
CsA (C0: 150–300 mg/l until M1, then 100–250) | Bela LI then 4w Bela MI then 4w |
(Total nb: 542) CsA: 184 LI: 175 MI: 183 | ECD Basiliximab for induction, steroids + MYC for maintenance |
7 years | (Total nb: 102) LI vs. CsA: HR 0.78 [0.45–1.35] MI vs. CsA: HR 0.70 [0.40–1.29] |
(Total nb: 73) LI vs. CsA: 0.78 [0.45–1.35] MI vs. CsA: 0.70 [0.40–1.23] | LI vs. CsA: HR 0.93 [0.63–1.36] MI vs. CsA: HR 0.92 [0.63–1.34] |
LI vs. CsA: HR 1.15 [0.70–1.90] MI vs. CsA: HR 1.22 [0.75–2.00] | (Death from CV cause) CsA: 8/184 LI: 12/175 MI: 12/183 (Serious events) CsA: 5.2/100py LI: 4.1/100py MI: 5.2/100py |
(Serious events) CsA: 20.3/100py LI: 16.5/100py MI: 22.7/100py | CsA: 3.6/100py LI: 3.2/100py MI: 3.8/100py |
| Ferguson et al. (12) | Tac/MYC (C0: 8–12 ng/ml until M1, then 5–10) | Bela/MYC Bela/Siro |
(Total nb: 89) Tac/MYC: 30 Bela/MYC: 33 Bela/Siro: 26 | rATG for induction No steroids for maintenance |
1 year | (Total nb: 1) Tac/MYC: 0/30 Bela/MYC: 1/33 Bela/Siro: 0/26 |
(Total nb: 3) Tac/MYC: 0/30 Bela/MYC: 1/33 Bela/Siro: 2/26 | Tac/MYC: 0/30 Bela/MYC: 2/33 Bela/Siro: 2/26 |
Tac/MYC: 1/30 Bela/MYC: 5/33 Bela/Siro: 1/26 | – | Tac/MYC: 5/30 Bela/MYC: 7/33 Bela/Siro: 4/26 | Tac/MYC: 1/30 Bela/MYC: 0/33 Bela/Siro: 1/26 |
| de Graav et al. (13) | Tac (C0: 10–15 ng/ml until S2, then 8–12 until M1, then 5–10) | Bela | (Total nb: 40) Tac: 20 Bela: 20 | Basiliximab for induction, steroids + MYC for maintenance | 1 year | (Total nb: 1) Tac: 1/20 Bela: 0/20 |
(Total nb: 3) Tac: 0/20 Bela: 3/20 | Tac: 1/20 Bela: 3/20 |
Tac: 2/20 Bela: 11/20 | Tac: 1.20/100py Bela: 0.95/100py |
Tac: 1.90/100py Bela: 2.25/100py | Tac: 0/100py Bela: 0/100py |
| Newell et al. (14) CTOT−10 |
Alem/Tac (C0: 8–12 ng/ml until M6, then 5–10) | Alem/Bela Bas/Tac/Bela: tacrolimus withdrawal in 3 months |
(Total nb: 19) Alem/Tac: 6 Alem/Bela: 6 Bas/Tac/Bela: 7 | No steroids for maintenance | 1 year | (Total nb: 1) Alem/Tac: 1/6 Alem/Bela: 0/6 Bas/Tac/Bela: 0/7 |
(Total nb: 4) Alem/Tac: 1/6 Alem/Bela: 3/6 Bas/Tac/Bela: 0/7 | Alem/Tac: 2/6 Alem/Bela: 3/6 Bas/Tac/Bela: 0/7 |
Alem/Tac: 3/6 Alem/Bela: 2/6 Bas/Tac/Bela: 5/7 | – | – | – |
| Stock et al. (15) CTOT−15 |
MYC/Tac (C0: 8–12 ng/ml until M6, then 5–8) | MYC/Tac/Bela: tacrolimus withdrawal, if possible, in 10 months | (Total nb: 43) MYC/Tac: 21 MYC/Tac/Bela: 22 | Combined kidney and pancreas transplantation rATG for induction No steroids for maintenance |
1 year | (Total nb: 1) MYC/Tac: 0/21 MYC/Tac/Bela: 1/22 |
(Total nb: 0) | MYC/Tac: 0/21 MYC/Tac/Bela: 1/22 |
(Treated episodes) MYC/Tac: 4/21 MYC/Tac/Bela: 4/22 | – | MYC/Tac: 15/21 MYC/Tac/Bela: 19/22 | – |
| Mannon et al. (16) CTOT−16 |
rATG/MYC/Tac (C0: 8–12 ng/ml until M6, then 5–8) | rATG/MYC/Bela Bas/Tac/MYC/ Bela: tacrolimus withdrawal in 3 months |
(Total nb: 68) rATG/MYC/Tac: 29 rATG/MYC/Bela: 29 Bas/Tac/MYC/ Bela: 10 |
No steroids for maintenance | 1 year | (Total nb: 2) rATG/MYC/Tac: 2/29 rATG/MYC/Bela: 0/29 Bas/Tac/MYC/Bela: 0/11 |
(Total nb: 0) | rATG/MYC/Tac: 2/29 rATG/MYC/Bela: 0/29 Bas/Tac/MYC/ Bela: 0/11 |
(Treated episodes) rATG/MYC/Tac: 7/29 rATG/MYC/Bela: 14/29 Bas/Tac/MYC/Bela: 4/11 | – | rATG/MYC/Tac: 14/29 rATG/MYC/Bela: 16/29 Bas/Tac/MYC/Bela: 3/11 | – |
| Kaufman et al. (17) BEST |
rATG/Tac (C0: 8–12 ng/ml until M1, then 5–10) | rATG/Bela Alem/Bela |
(Total nb: 333) rATG/Tac: 105 rATG/Bela: 104 Alem/Bela: 107 | No steroids for maintenance | 2 years | (Total nb: 7) rATG/Tac: 1/105 rATG/Bela: 4/104 Alem/Bela: 2/107 |
(Total nb: 2) rATG/Tac: 1/105 rATG/Bela: 1/104 Alem/Bela: 0/107 | rATG/Tac: 2/105 rATG/Bela: 5/104 Alem/Bela: 2/107 |
rATG/Tac: 7/105 rATG/Bela: 26/104 Alem/Bela: 20/107 | (Serious events) rATG/Tac: 3/105 rATG/Bela: 10/104 Alem/Bela: 1/107 |
(Serious events) rATG/Tac: 22/105 rATG/Bela: 24/104 Alem/Bela: 24/107 | rATG/Tac: 7/105 rATG/Bela: 6/104 Alem/Bela: 7/107 |
| Belatacept vs. CNI, for stable KT recipients already on CNI | ||||||||||||
| Grinyo et al. (7) | CNI (CsA or Tac) | Bela: 5 mg/kg 5 inj./2 months, then every 4w | (Total nb: 173) CNI: 89 Bela: 84 | 6–36 months after KT eGFR 35–75 ml/min |
3 years | (Total nb: 2) CNI: 1/89 Bela: 1/84 |
(Total nb: 2) CNI: 1/89 Bela: 1/84 | CNI: 2/89 Bela: 2/84 |
CNI: 3/89 Bela: 7/84 | – | (Serious events) CNI: 10.2/100py Bela: 9.3/100py | CNI: 3.4/100py Bela: 3.0/100py |
| Budde et al. (8) | CNI (CsA or Tac) | Bela | (Total nb: 666) CNI: 223 Bela: 223 | 6–60 months after KT eGFR 30–75 ml/min |
2 years | (Total nb: 8) CNI: 4/223 Bela: 4/223 |
(Total nb: 2) CNI: 2/223 Bela: 0/223 | CNI: 6/223 Bela: 4/223 |
CNI: 9/223 Bela: 18/223 | (Death from CV cause) CNI: 1/223 Bela: 3/223 |
(Serious events) CNI: 44/222 Bela: 37/221 | CNI: 12/222 Bela: 18/221 |
| Comparison of belatacept regimens, for stable KT recipients already on belatacept | ||||||||||||
| Badell et al. (18) | Bela 4w | Bela 8w | (Total nb: 163) 4w: 82 8w: 81 | >12 months after KT eGFR >35 ml/min |
1 year | (Total nb: 2) 4w: 2/82 8w: 0/81 |
(Total nb: 0) 4w: 0/82 8w: 0/81 | 4w: 2/82 8w: 0/81 |
4w: 2/82 8w: 5/81 | – | (Any event) 4w: 24/82 8w: 23/81 | 4w: 1/82 8w: 4/81 |
When several articles were published on the same trial, only the one with the longest follow-up time was considered. Statistically significant differences are highlighted in bold. Bela: belatacept. LI, less intensive: MI, more intensive; CsA, cyclosporin A; Tac, tacrolimus; CNI, calcineurin inhibitors; KT, kidney transplant; MYC, mycophenolate mofetil or mycophenolic acid; rATG, rabbit antithymocyte globulin; Alem, alemtuzumab; Bas, basiliximab; HR, hazard ratio; Py, patient-year.