Early outcomes of thymoglobulin and basiliximab induction in kidney transplantation: application of statistical approaches to reduce bias in observational comparisons.
BACKGROUND
Retrospective comparison of treatment-related kidney transplant outcomes may be facilitated by multivariable statistical adjustments and case-matching.


METHODS
We studied Organ Procurement and Transplantation Network registry data for kidney transplants in 2001 to 2005 managed with thymoglobulin, basiliximab, or no antibody induction and discharge maintenance immunosuppression regimens of tacrolimus and mycophenolate mofetil. The primary outcome was the 6 month, Food and Drug Administration-approved composite endpoint of rejection, graft failure, or death. Outcomes according to induction exposure were compared using logistic regression analysis, exposure likelihood matching, and outcome risk score matching.


RESULTS
All statistical approaches demonstrated lower rates of the 6-month triple endpoint with thymoglobulin compared with basiliximab when steroids were present, with approximately 22% adjusted, relative reduction by logistic regression analysis and 3% absolute reductions by matching approaches. When steroids were absent, risk reduction among thymoglobulin versus basiliximab-treated patients was of larger magnitude but borderline statistical significance. Triple endpoint incidence was lower with both induction regimens compared with no induction across methods. Estimated sample sizes necessary to detect the observed differences between induction types in the presence of steroids in a prospective trial ranged from 1600 to nearly 7000 patients.


CONCLUSIONS
Consistency across statistical approaches suggests superiority of thymoglobulin compared with basiliximab or no antibody induction therapy for 6-month kidney transplant outcomes in the modern immunosuppression era. As the sample sizes necessary to power a prospective superiority trial are likely prohibitive, studies such as these provide clinically relevant information that may not be otherwise attainable.
Willoughby
Lisa M
LM
Department of Research Methodology, Saint Louis University, St. Louis, MO 63130, USA.
Schnitzler
Mark A
MA
Brennan
Daniel C
DC
Pinsky
Brett W
BW
Dzebisashvili
Nino
N
Buchanan
Paula M
PM
Neri
Luca
L
Rocca-Rey
Lisa A
LA
Abbott
Kevin C
KC
Lentine
Krista L
KL
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D000077552:Basiliximab; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D013997:Time Factors; D014019:Tissue Donors / Q000706:statistics & numerical data; D016896:Treatment Outcome; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab