Belatacept for kidney transplant recipients.
Author(s): Masson P(1), Henderson L, Chapman JR, Craig JC, Webster AC.
Affiliation(s): Author information:
(1)Sydney School of Public Health, The University of Sydney, Sydney, Australia.
Publication date & source: 2014, Cochrane Database Syst Rev. , 11:CD010699
BACKGROUND: Most people who receive a kidney transplant die from either
cardiovascular disease or cancer before their transplant fails. The most common
reason for someone with a kidney transplant to lose the function of their
transplanted kidney necessitating return to dialysis is chronic kidney transplant
scarring. Immunosuppressant drugs have side effects that increase risks of
cardiovascular disease, cancer and chronic kidney transplant scarring. Belatacept
may provide sufficient immunosuppression while avoiding unwanted side effects of
other immunosuppressant drugs. However, high rates of post-transplant
lymphoproliferative disease (PTLD) have been reported when belatacept is used in
particular kidney transplant recipients at high dosage.
OBJECTIVES: 1) Compare the relative efficacy of belatacept versus any other
primary immunosuppression regimen for preventing acute rejection, maintaining
kidney transplant function, and preventing death. 2) Compare the incidence of
several adverse events: PTLD; other malignancies; chronic transplant kidney
scarring (IF/TA); infections; change in blood pressure, lipid and blood sugar
control. 3) Assess any variation in effects by study, intervention and recipient
characteristics, including: differences in pre-transplant Epstein Barr virus
serostatus; belatacept dosage; and donor-category (living, standard criteria
deceased, or extended criteria deceased).
SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 1
September 2014 through contact with the Trials' Search Co-ordinator using search
terms relevant to this review.
SELECTION CRITERIA: Randomised controlled trials (RCT) that compared belatacept
versus any other immunosuppression regimen in kidney transplant recipients were
eligible for inclusion.
DATA COLLECTION AND ANALYSIS: Two authors independently extracted data for study
quality and transplant outcomes and synthesized results using random effects
meta-analysis, expressed as risk ratios (RR) and mean differences (MD), both with
95% confidence intervals (CI). Subgroup analyses and univariate meta-regression
were used to investigate potential heterogeneity.
MAIN RESULTS: We included five studies that compared belatacept and calcineurin
inhibitors (CNI) that reported data from a total of 1535 kidney transplant
recipients. Of the five studies, three (478 participants) compared belatacept and
cyclosporin and two (43 recipients) compared belatacept and
tacrolimus. Co-interventions included basiliximab (4 studies, 1434 recipients);
anti-thymocyte globulin (1 study, 89 recipients); alemtuzumab (1 study, 12
recipients); mycophenolate mofetil (MMF, 5 studies, 1509 recipients); sirolimus
(1 study, 26 recipients) and prednisone (5 studies, 1535 recipients).Up to three
years following transplant, belatacept and CNI-treated recipients were at similar
risk of dying (4 studies, 1516 recipients: RR 0.75, 95% CI 0.39 to 1.44), losing
their kidney transplant and returning to dialysis (4 studies, 1516 recipients: RR
0.91, 95% CI 0.61 to 1.38), and having an episode of acute rejection (4 studies,
1516 recipients: RR 1.56, 95% CI 0.85 to 2.86). Belatacept-treated kidney
transplant recipients were 28% less likely to have chronic kidney scarring (3
studies, 1360 recipients: RR 0.72, 95% CI 0.55 to 0.94) and also had better graft
function (measured glomerular filtration rate (GFR) (3 studies 1083 recipients):
10.89 mL/min/1.73 m², 95% CI 4.01 to 17.77; estimated GFR (4 studies, 1083
recipients): MD 9.96 mL/min/1.73 m², 95% CI 3.28 to 16.64) than CNI-treated
recipients. Blood pressure was lower (systolic (2 studies, 658 recipients): MD
-7.51 mm Hg, 95% CI -10.57 to -4.46; diastolic (2 studies, 658 recipients): MD
-3.07 mm Hg, 95% CI -4.83 to -1.31, lipid profile was better (non-HDL (3 studies
1101 recipients): MD -12.25 mg/dL, 95% CI -17.93 to -6.57; triglycerides (3
studies 1101 recipients): MD -24.09 mg/dL, 95% CI -44.55 to -3.64), and incidence
of new-onset diabetes after transplant was reduced by 39% (4 studies (1049
recipients): RR 0.61, 95% CI 0.40 to 0.93) among belatacept-treated versus
CNI-treated recipients.Risk of PTLD was similar in belatacept and CNI-treated
recipients (4 studies, 1516 recipients: RR 2.79, 95% CI 0.61 to 12.66) and was no
different among recipients who received different belatacept dosages (high versus
low dosage: ratio of risk ratios (RRR) 1.06, 95% CI 0.11 to 9.80, test of
difference = 0.96) or among those who were Epstein Barr virus seronegative
compared with those who were seropositive before their kidney transplant
(seronegative versus seropositive; RRR 1.49, 95% CI 0.15 to 14.76, test for
difference = 0.73).The belatacept dose used (high versus low), type of donor
kidney the recipient received (extended versus standard criteria) and whether the
kidney transplant recipient received tacrolimus or cyclosporin made no difference
to kidney transplant survival, incidence of acute rejection or estimated GFR.
Selective outcome reporting meant that data for some key subgroup comparisons
were sparse and that estimates of the effect of treatment in these groups of
recipients remain imprecise.
AUTHORS' CONCLUSIONS: There is no evidence of any difference in the effectiveness
of belatacept and CNI in preventing acute rejection, graft loss and death, but
treatment with belatacept is associated with less chronic kidney scarring and
better kidney transplant function. Treatment with belatacept is also associated
with better blood pressure and lipid profile and a lower incidence of diabetes
versus treatment with a CNI. Important side effects (particularly PTLD) remain
poorly reported and so the relative benefits and harms of using belatacept remain
unclear. Whether short-term advantages of treatment with belatacept are
maintained over the medium- to long-term or translate into better cardiovascular
outcomes or longer kidney transplant survival with function remains unclear.
Longer-term, fully reported and published studies comparing belatacept versus
tacrolimus are needed to help clinicians decide which patients might benefit most
from using belatacept.
|