Co-stimulatory blockade with belatacept in kidney transplantation

Figures & data

Figure 1. Mechanism of action of belatacept.

Table 1. Graft outcomes in belatacept studies.

Clinical trials	Phase III, BENEFIT [4] (0 – 12 months) n = 666			Phase III, BENEFIT-EXT [5] (0 – 12 months) n = 543			BENEFIT long-term extension [10] (36 – 60 months) n = 456			BENEFIT-EXT long-term extension [11] (36 – 60 months) n = 304
MI	LI	CsA	MI	LI	CsA	MI	LI	CsA	MI	LI	CsA
Death-censored graft loss %	2	2	4	9	9	11	0	0	2.2	1.9	0.8	5.7
Death with function graft %	3	1	3	3	2	3	1.9	1.2	5.1	4.8	7.9	6.9
Mean GFR (ml/min)*	65	63.4	50.4	52	49.5	45.2	74.1	76.4	53	55.9	59	44.6
Acute rejection (%)*	22	17	7	18	17.7	14.1	0	0	0	1.9	0.8	0
Decline of GFR with time Slope (ml/min/year)*				-0.9	-0.6	-1.9

*p < 0.05 (belatacept vs CsA).

BENEFIT: Belatacept evaluation of nephroprotection and efficacy as a first-line immunosuppression trial; CsA: Cyclosporine A; GFR: Glomerular filtration rate; LI: Less intensive; MI: More intensive.

Table 2. Adverse outcomes in belatacept studies.

Clinical trials	Phase III, BENEFIT [4] (0 – 12 months) n = 666			Phase III, BENEFIT-EXT [5] (0 – 12 months) n = 543			BENEFIT long-term extension [10] (36 – 60 months) n = 456			BENEFIT-EXT long-term extension [11] (36 – 60 months) n = 304
MI	LI	CsA	MI	LI	CsA	MI	LI	CsA	MI	LI	CsA
Serious adverse events, %	51	44	57	Si	Si	Si	35.5	31.5	39	46	58	51
Frequency of infection, %	69	70	71	79	82	82	16.8	15.2	19.1	42	44	51
Serious infectious adverse events, %	20	19	21	48	41	46	-	-	-	-	-	-
Urinary tract infection, %	25	28	23	10.3	12.6	9.8	3.9	3.0	3.7	5	4	6
CMV, %	6	8	9	11	14	13	21.3	16.2	17.6	4	4	3
BK virus, %	5	1	4	Si	Si	Si				4	1	1
Fungal infections, %	6	3	6	4.3	2.8	7	14.2	15.2	11.8	12	17	14
Malignancies, %	2	2	1	2	2	3	5.2	7.3	8.8	3	5	3
PTLD, %*	1	1	0	1.1	1.7	0	0	0	0	0	2.6	1.14
Mean blood pressure* (mmHg)	133/79	131/79	139/82	141/78	141/78	150/82	125/73	126/76	134/80	133/74	132/75	142/78
NODAT %	11	7	16	2	5	9	-	-	-	-	-	-
Mean Δ from baseline non-HDL* (mg/dl)	8.1	8.0	18.3	12.6	11.2	29.3	-9.7	-7.4	13.1	+0.1	-0.1	+10

*p < 0.05 (belatacept vs CsA).

CMV: Cytomegalovirus; LI: Less intensive; MI: More intensive; NODAT: New onset diabetes after transplant; PTLD: Posttransplant lymphoproliferative disorder; Si: Similar among groups.

Table 3. Guidelines for belatacept use.

Reasonable to consider belatacept	Avoid belatacept
Non-sensitized patients receiving ECD/DCD kidneys	EBV seronegative recipients due to elevated risk for the development of PTLD
Patients receiving zero-mismatch kidneys
	High immune risk patients such as those with previous rejections, high PRA or DSA
Patients in whom noncompliance with oral medications is a major concern for graft loss
Patients who developed CNI-induced thrombotic microangiopathy in renal allograft

CNI: Calcineurin inhibitor; DCD: Donation after cardiac death; ECD: Expanded criteria donor; DSA: Donor-specific antibody; PRA: Panel reactive antibody; PTLD: Posttransplant lymphoproliferative disorder.

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