title: A randomized, double-blinded comparison of Thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients.
abstract: BACKGROUND
  The aim of this study was to compare the efficacy and safety of Thymoglobulin (a rabbit-derived polyclonal antibody) to Atgam (a horse-derived polyclonal antibody) for induction in adult renal transplant recipients.
  
  
  METHODS
  Transplant recipients (n=72) were randomized 2:1 in a double-blinded fashion to receive Thymoglobulin (n=48) at 1.5 mg/kg intravenously or Atgam (n=24) at 15 mg/kg intravenously, intraoperatively, then daily for at least 6 days. Recipients were observed for at least 1 year of follow-up.
  
  
  RESULTS
  By 1 year after transplantation, 4% of Thymoglobulin-treated patients experienced acute rejection compared with 25% of Atgam-treated patients (P=0.014). The rate of acute rejection was lower with Thymoglobulin than Atgam (relative risk=0.09; P=0.009). Rejection was less severe with Thymoglobulin than Atgam (P=0.02). No recurrent rejection occurred with Thymoglobulin compared with 33% with Atgam (P=NS). Patient survival was not different, but the composite end point of freedom from death, graft loss, or rejection, the "event-free survival," was superior with Thymoglobulin (94%) compared with Atgam (63%; P=0.0005). Fewer adverse events occurred with Thymoglobulin (P=0.013). Leukopenia was more common with Thymoglobulin than Atgam (56% vs. 4%; P<0.0001) during induction. The mean absolute lymphocyte count remained below baseline with Thymoglobulin throughout the study (P<0.007), but with Atgam, significant lymphocyte reductions occurred only at day 7. The incidence of cytomegalovirus disease was less with Thymoglobulin than Atgam at 6 months (10% vs. 33%; P=0.025).
  
  
  CONCLUSIONS
  Brief (7-day) induction with Thymoglobulin resulted in less frequent and less severe rejection, a better event-free survival, less cytomegalovirus disease, fewer serious adverse events, but more frequent early leukopenia than induction with Atgam. These results may in fact be explained by a more profound and durable beneficial lymphopenia.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. brennand@msnotes.wustl.edu
authors.forename: D C
authors.initials: DC
authors.lastname: Brennan
authors.forename: K
authors.initials: K
authors.lastname: Flavin
authors.forename: J A
authors.initials: JA
authors.lastname: Lowell
authors.forename: T K
authors.initials: TK
authors.lastname: Howard
authors.forename: S
authors.initials: S
authors.lastname: Shenoy
authors.forename: S
authors.initials: S
authors.lastname: Burgess
authors.forename: S
authors.initials: S
authors.lastname: Dolan
authors.forename: J M
authors.initials: JM
authors.lastname: Kano
authors.forename: M
authors.initials: M
authors.lastname: Mahon
authors.forename: M A
authors.initials: MA
authors.lastname: Schnitzler
authors.forename: R
authors.initials: R
authors.lastname: Woodward
authors.forename: W
authors.initials: W
authors.lastname: Irish
authors.forename: G G
authors.initials: GG
authors.lastname: Singer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000032:analysis; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D015994:Incidence; D007231:Infant, Newborn; D016030:Kidney Transplantation; D007958:Leukocyte Count; D008875:Middle Aged; D016019:Survival Analysis
chemical_list: D000906:Antibodies; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents