title: Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial.
abstract: BACKGROUND
  In a phase 2 study, kidney transplant recipients of low immunologic risk who switched from a calcineurin inhibitor (CNI) to belatacept had improved kidney function at 12 months postconversion versus those continuing CNI therapy, with a low rate of acute rejection and no transplant loss.
  
  
  METHODS
  36-month follow-up of the intention-to-treat population.
  
  
  METHODS
  CNI-treated adult kidney transplant recipients with stable transplant function (estimated glomerular filtration rate [eGFR], 35-75mL/min/1.73m2).
  
  
  METHODS
  At 6 to 36 months posttransplantation, patients were randomly assigned to switch to belatacept-based immunosuppression (n=84) or continue CNI-based therapy (n=89).
  
  
  RESULTS
  Safety was the primary outcome. eGFR, acute rejection, transplant loss, and death were also assessed.
  
  
  METHODS
  Treatment exposure-adjusted incidence rates for safety, repeated-measures modeling for eGFR, Kaplan-Meier analyses for efficacy.
  
  
  RESULTS
  Serious adverse events occurred in 33 (39%) belatacept-treated patients and 36 (40%) patients in the CNI group. Treatment exposure-adjusted incidence rates for serious infections (belatacept vs CNI, 10.21 vs 9.31 per 100 person-years) and malignancies (3.01 vs 3.41 per 100 person-years) were similar. More patients in the belatacept versus CNI group had any-grade viral infections (14.60 vs 11.00 per 100 person-years). No posttransplantation lymphoproliferative disorder was reported. Belatacept-treated patients had a significantly greater estimated gain in mean eGFR (1.90 vs 0.07mL/min/1.73m2per year; P for time-by-treatment interaction effect = 0.01). The probability of acute rejection was not significantly different for belatacept (8.38% vs 3.60%; HR, 2.50 [95% CI, 0.65-9.65; P=0.2). HR for the comparison of belatacept to the CNI group for time to death or transplant loss was 1.00 (95% CI, 0.14-7.07; P=0.9).
  
  
  CONCLUSIONS
  Exploratory post hoc analysis with a small sample size.
  
  
  CONCLUSIONS
  Switching patients from a CNI to belatacept may represent a safe approach to immunosuppression and is being further explored in an ongoing phase 3b trial.
authors.affiliation: University of Barcelona, IDIBELL, Barcelona, Spain. Electronic address: jgrinyo@ub.edu.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grinyó
authors.affiliation: Instituto de Nefrologia, Buenos Aires, Argentina.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Carmen Rial
authors.affiliation: Instituto Nacional de Ciencias Medicas y Nutricion, Tlalpan, Mexico.
authors.forename: Josefina
authors.initials: J
authors.lastname: Alberu
authors.affiliation: Balboa Institute of Transplantation, San Diego, CA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Roberto C
authors.initials: RC
authors.lastname: Manfro
authors.affiliation: Lakeshore Hospital, Kochi, India.
authors.forename: Georgy
authors.initials: G
authors.lastname: Nainan
authors.affiliation: UCSF Transplant Service, San Francisco, CA.
authors.forename: Flavio
authors.initials: F
authors.lastname: Vincenti
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Jones-Burton
authors.affiliation: Toulouse University Hospital, Toulouse, France.
authors.forename: Nassim
authors.initials: N
authors.lastname: Kamar
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use*; D000328:Adult; D065095:Calcineurin Inhibitors / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D057915:Drug Substitution; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007239:Infections / Q000139:chemically induced* / Q000276:immunology; D016030:Kidney Transplantation; D008232:Lymphoproliferative Disorders / Q000139:chemically induced / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009369:Neoplasms / Q000139:chemically induced* / Q000276:immunology; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000069594:Abatacept; D016572:Cyclosporine; D016559:Tacrolimus
keywords: Kidney transplant; acute rejection; adverse events; belatacept; calcineurin inhibitor (CNI); conversion study; graft loss; immunosuppression; kidney function; phase 2 randomized controlled trial; renal transplantation; safety; switch