title: A three-arm study comparing immediate tacrolimus therapy with antithymocyte globulin induction therapy followed by tacrolimus or cyclosporine A in adult renal transplant recipients.
abstract: 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.
authors.affiliation: Service de Néphrologie, Hôpital de Bicêtre, Le Kremlin Bicêtre, France. bernard.charpentier@bct.ap-hop-paris.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Charpentier
authors.forename: Lionel
authors.initials: L
authors.lastname: Rostaing
authors.forename: Francois
authors.initials: F
authors.lastname: Berthoux
authors.forename: Philippe
authors.initials: P
authors.lastname: Lang
authors.forename: Giovanni
authors.initials: G
authors.lastname: Civati
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Touraine
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Squifflet
authors.forename: Paul
authors.initials: P
authors.lastname: Vialtel
authors.forename: Daniel
authors.initials: D
authors.lastname: Abramowicz
authors.forename: Georges
authors.initials: G
authors.lastname: Mourad
authors.forename: Philippe
authors.initials: P
authors.lastname: Wolf
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cassuto
authors.forename: Bruno
authors.initials: B
authors.lastname: Moulin
authors.forename: Gerard
authors.initials: G
authors.lastname: Rifle
authors.forename: André
authors.initials: A
authors.lastname: Pruna
authors.forename: Pierre
authors.initials: P
authors.lastname: Merville
authors.forename: Françoise
authors.initials: F
authors.lastname: Mignon
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.forename: Patrick
authors.initials: P
authors.lastname: Le Pogamp
authors.forename: Yvon
authors.initials: Y
authors.lastname: Lebranchu
authors.forename: Olivier
authors.initials: O
authors.lastname: Toupance
authors.forename: Bruno
authors.initials: B
authors.lastname: Hurault De Ligny
authors.forename: Guy
authors.initials: G
authors.lastname: Touchard
authors.forename: Michel
authors.initials: M
authors.lastname: Olmer
authors.forename: Raj
authors.initials: R
authors.lastname: Purgus
authors.forename: Claire
authors.initials: C
authors.lastname: Pouteil-Noble
authors.forename: Denis
authors.initials: D
authors.lastname: Glotz
authors.forename: Bernard
authors.initials: B
authors.lastname: Bourbigot
authors.forename: Michel
authors.initials: M
authors.lastname: Leski
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Wauters
authors.forename: Michèle
authors.initials: M
authors.lastname: Kessler
mesh_terms: 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
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus