Anti-thymocyte globulin for treatment of T-cell-mediated allograft rejection

Table 1 Summary of randomized clinical trial studies

No.	Ref.	Study design	ATG – dose & duration	Graft outcome		Death	Other adverse events
1	Shield et al[50], 1979	Prospective, randomised, single centre, United States; First rejection	eATG 15 mg/kg daily for 14 d (n = 10) vs MP 1 g/d for 5 d (n = 10)	Reversal – 8/10 (ATG) vs 6/10 (MP); Recurrent rejection 1/10 (ATG) vs 5/10 (MP); Graft loss at 12 mo – 1/10 (ATG) vs 1/10 (MP)		At 12 mo – 0/10 (ATG) vs 1/10 (MP)	Infection – 3/10 (ATG) vs 0/10 (MP); AVN – 1/10 (ATG) vs 0/10 (MP)
2	Filo et al[51], 1980	Prospective, randomised, single centre, United States; First rejection	eATG 10 mg/kg/d for 15 d (n = 35) vs MP 30 mg/kg every other day up to 5 doses (n = 43)	Reversal – 32/35 (ATG) vs 29/43 (MP); Recurrent rejection – 16/35 (ATG) vs 15/43 (MP); Graft survival (91% vs 62%); Faster recovery (6.9 d vs 8.9 d); Graft loss – 15/35 vs 25/43 (MP)		At 12 mo – 1/24 (ATG) vs 0/29 (MP)
3	Hoitsma et al[52], 1982	Prospective, randomised, single centre, Netherlands; First rejection	rATG initially 4 mg/kg followed by 2-7 mg/kg for 21 d (n = 20) vs prednisolone 200 mg/d, tapered to 25 mg/d in 2 wk (n = 20)	Reversal – 43/50 (ATG) vs 35/50 (Prednisolone); Recurrent rejection – 28/50 (ATG) vs 35/50 (Prednisolone); Graft loss – 15/50 (ATG) vs 28/50 (Prednisolone)		At 12 mo – 0/20 (ATG) vs 1/20 (Prednisolone)	Infection – 9/20 (ATG) vs 15/20 (Prednisolone)
4	Toledo-Pereyra et al[53], 1985	Prospective, randomised, single centre, United States; First rejection	ALG 10 to 20 mg/kg for 10 d (n = 20) vs ATG 10 to 20 mg/kg for 10 d (n = 20)	Reversal – 15/20 (ALG) vs 16/20 (ATG)
6	Alamartine et al[54], 1994	Prospective randomised, single centre, France; Steroid-resistant rejection	Muromonab-CD3 5 mg/d for 10 d (n = 27) vs rATG: 1.5 mg/kg/d for 10 d (n = 32)		Reversal – 25/26 (Muromonab-CD3) vs 27/32 (ATG); Recurrent rejection – 25/32 (ATG) vs 24/27 (Muromonab-CD3); Graft loss at 12 mo – 11/32 (ATG) vs 4/26 (Muromonab-CD3)		CMV infection – 8/27 (Muromonab-CD3) vs 18/32 (ATG)
7	Tesi et al[55], 1997	Prospective, randomised, multi-centre n = 163 (82 Thymoglobulin, 81 ATGAM); First rejection	rATG 1.5 mg/kg vs ATGAM 15 mg/kg (both for 7 to 14 d)	65% treated with THYMO had histology grade improvement (vs 50% in ATGAM)		Overall – 3/82 (rATG) vs 1/81 (eATG)	CMV infection 20/82 in both groups
8	Mariat et al[31], 1998	Prospective, randomised, single centre, France; First rejection	Muromonab-CD3 5 mg/kg for 3 d followed by 2.5 mg/kg for 7 d (n = 29) vs rATG 25 mg/d if < 40 kg, 50 mg/d if 40-70 kg & 75 mg/d if > 70 kg; 10 d (n = 31)	Reversal – 25/29 (Muromonab-CD3) vs 30/31 (ATG); Recurrent rejection – 11/29 (Muromonab-CD3) vs 9/31 (ATG); Graft loss at 12 mo – 6/29 (Muromonab-CD3) vs 4/31 (ATG)		At 12 mo – 3/31 (ATG) vs 1/29 (Muromonab-CD3)	CMV infection – 12/31 (ATG) vs 13/29 (Muromonab-CD3); Malignancy – 0/31 (ATG) vs 2/29 (Muromonab-CD3)
9	Gaber et al[56], 1998	Prospective, randomised, multi centre, United States; First rejection	Thymoglobulin (rATG) 1.5 mg/kg/d for 7-14 d (n = 82) vs ATGam (eATG) 15 mg/kg/d, for 7-14 d (n = 81)	Reversal – 88% (Thymoglobulin) vs 76% (ATGAM); Recurrent rejection; 28/82 (rATG) vs 50/81 (eATG)		Total 6/82 (rATG) vs 3/81 (eATG)	Leukopenia – 57% (rATG) vs 30% (eATG); Bacterial infection – 29% (rATG) vs 37% e(ATG); Viral infection – 21% (rATG) vs 11% (eATG)
10	Theodorakis et al[57], 1998	Prospective, randomised, single centre, Germany; First rejection	ATG 4 mg/kg for 7 d (n = 25) vs MP 250 mg/d for 3 d (n = 25)	Recurrent rejection – 4/25 (ATG) vs 18/25 (MP); Graft loss – 5/25 (ATG) vs 3/25 (MP)
11	Baldi et al[58], 2000	Prospective, randomised, single center, Belgium; First rejection	rATG 4 mg/kg day for 10 d (n = 28) vs Muromonab-CD3: 5 mg/d for 10 d (n = 28); MP for both groups: 500 mg/d for 3 d	Reversal – 21/28 (rATG) vs 14/28 (Muromonab-CD3); Recurrent rejection – 9/28 (ATG) vs 10/25 (Muromonab-CD3)		Irreversible rejection in 3/28 OKT3, 2nd rejection in 33% ATG, 39% OKT3	Fever – 21.4% (ATG) vs 92.8% (Muromonab-CD3); Headache – 3.5% (ATG) vs 46.4% (Muromonab-CD3); Infection – 9/28 (ATG) vs 10/28 (Muromonab-CD3); Malignancy 2/28 (ATG) vs 0/28 (Muromonab-CD3)
12	Midtvedt et al[59], 2003	Prospective, randomised, single centre, Norway; First rejection	ATG 2 mg/kg followed by 1 mg/kg if & when T cells > 50 (n = 27) vs muromonab-CD3: 5 mg, then 2.5 mg (n = 28)	Reversal – 26/27 (ATG) vs 27/28 (Muromonab-CD3); Recurrent rejection – 12/27 (ATG) vs 14/28 (Muromonab-CD3); Grafts loss at 12 mo – 3/27 (ATG) vs 4/28 (Muromonab-CD3)		At 12 mo – 2/27 (ATG) vs 1/28 (Muromonab-CD3)	CMV infection – 14/27 (ATG) vs 11/28 (Muromonab-CD3); Malignancy – 1/27 (ATG) vs 1/28 (muromonab-CD3); Bacterial pneumonia – 3/27 (ATG) vs 3/28 (Muromonab-CD3)

ATG: Anti-thymocyte globulin; rATG: Rabbit Anti-thymocyte globulin, eATG: Equine Anti-thymocyte globulin; MP: Methylprednisone.