A three-arm study comparing immediate tacrolimus therapy with antithymocyte globulin induction therapy followed by tacrolimus or cyclosporine A in adult renal transplant recipients.
BACKGROUND
Induction therapy with antithymocyte globulin (ATG) reduces the incidence of acute rejection after transplantation. A study was undertaken to assess the efficacy and safety of ATG induction on tacrolimus-based and cyclosporine A (CsA)-based therapies compared with immediate tacrolimus triple therapy in kidney transplant recipients.


METHODS
In a 6-month, open-label, randomized, prospective study conducted in 30 European centers, 555 renal transplant patients were randomly assigned to tacrolimus triple therapy (Tac triple, n=185), ATG induction with tacrolimus (ATG-Tac, n=186), or ATG induction with CsA microemulsion (ATG-CsA, n=184); all were combined with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection episode confirmed by biopsy.


RESULTS
Patient demographics and clinical parameters at baseline were similar. Patient and graft survival rates were similar in all groups. The incidence of clinically apparent acute rejection was significantly higher (P=0.003) for Tac triple (33.0%) compared with ATG-Tac (22.6%) and the incidence for ATG-Tac was significantly lower (P=0.004) than for ATG-CsA (37.0%). The incidences of acute rejection confirmed by biopsy (primary endpoint) were 25.4%, 15.1%, and 21.2% for Tac triple, ATG-Tac, and ATG-CsA, respectively (Tac triple vs. ATG-Tac, P=0.004). The incidences of corticosteroid-resistant acute rejection were 7.0% (Tac triple), 4.8% (ATG-Tac), and 10.9% (ATG-CsA) (ATG-Tac vs. ATG-CsA, P=0.038). In the ATG groups, the incidences of leukopenia, thrombocytopenia, serum sickness, fever, and cytomegalovirus infection were significantly higher (P<0.05).


CONCLUSIONS
Acute rejection was significantly lower in the ATG-Tac group compared with the ATG-CsA and Tac triple groups. Significantly more hematologic and infectious adverse events were observed in both ATG induction groups.
Charpentier
Bernard
B
Service de Néphrologie, Hôpital de Bicêtre, Le Kremlin Bicêtre, France. bernard.charpentier@bct.ap-hop-paris.fr.
Rostaing
Lionel
L
Berthoux
Francois
F
Lang
Philippe
P
Civati
Giovanni
G
Touraine
Jean-Louis
JL
Squifflet
Jean-Paul
JP
Vialtel
Paul
P
Abramowicz
Daniel
D
Mourad
Georges
G
Wolf
Philippe
P
Cassuto
Elisabeth
E
Moulin
Bruno
B
Rifle
Gerard
G
Pruna
André
A
Merville
Pierre
P
Mignon
Françoise
F
Legendre
Christophe
C
Le Pogamp
Patrick
P
Lebranchu
Yvon
Y
Toupance
Olivier
O
Hurault De Ligny
Bruno
B
Touchard
Guy
G
Olmer
Michel
M
Purgus
Raj
R
Pouteil-Noble
Claire
C
Glotz
Denis
D
Bourbigot
Bernard
B
Leski
Michel
M
Wauters
Jean-Pierre
JP
Kessler
Michèle
M
D000208:Acute Disease; D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage* / Q000009:adverse effects; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015994:Incidence; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011446:Prospective Studies; D016019:Survival Analysis; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus