Costimulation blockade with belatacept in renal transplantation.
BACKGROUND
Renal transplantation is the standard of care for patients with end-stage renal disease. Although maintenance immunosuppression with calcineurin inhibitors yields excellent one-year survival, it is associated over the long term with high rates of death and graft loss, owing in part to the adverse renal, cardiovascular, and metabolic effects of these agents. The use of potentially less toxic agents, such as belatacept, a selective blocker of T-cell activation, may improve outcomes.


METHODS
We randomly assigned renal-transplant recipients to receive an intensive or a less-intensive regimen of belatacept or cyclosporine. All patients received induction therapy with basiliximab, mycophenolate mofetil, and corticosteroids. The primary objective was to demonstrate the noninferiority of belatacept over cyclosporine in the incidence of acute rejection at six months (with an upper bound of the 95 percent confidence interval around the treatment difference of less than 20 percent).


RESULTS
At six months, the incidence of acute rejection was similar among the groups: 7 percent for intensive belatacept, 6 percent for less-intensive belatacept, and 8 percent for cyclosporine. At 12 months, the glomerular filtration rate was significantly higher with both intensive and less-intensive belatacept than it was with cyclosporine (66.3, 62.1, and 53.5 ml per minute per 1.73 m2, respectively), and chronic allograft nephropathy was less common with both regimens of belatacept than with cyclosporine (29 percent, 20 percent, and 44 percent, respectively). Lipid levels and blood-pressure values were similar or slightly lower in the belatacept groups, despite the greater use of lipid-lowering and antihypertensive medications in the cyclosporine group.


CONCLUSIONS
Belatacept, an investigational selective costimulation blocker, did not appear to be inferior to cyclosporine as a means of preventing acute rejection after renal transplantation. Belatacept may preserve the glomerular filtration rate and reduce the rate of chronic allograft nephropathy.
Vincenti
Flavio
F
University of California, San Francisco, San Francisco, USA.
Larsen
Christian
C
Durrbach
Antoine
A
Wekerle
Thomas
T
Nashan
Björn
B
Blancho
Gilles
G
Lang
Philippe
P
Grinyo
Josep
J
Halloran
Philip F
PF
Solez
Kim
K
Hagerty
David
D
Levy
Elliott
E
Zhou
Wenjiong
W
Natarajan
Kannan
K
Charpentier
Bernard
B
D000208:Acute Disease; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D060908:CTLA-4 Antigen; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation; D008055:Lipids / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes; D014184:Transplantation, Homologous
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007166:Immunosuppressive Agents; D008055:Lipids; D016572:Cyclosporine