Early outcomes of thymoglobulin and basiliximab induction in kidney transplantation: application of statistical approaches to reduce bias in observational comparisons

Abstract

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.

Figure 1

Observed frequencies of individual components of the triple endpoint by induction regimen, with and without discharge corticosteroids.

Figure 2

Exposure likelihood and outcome risk-matched comparisons of six-month triple endpoint by induction regimen and discharge steroid use. * p<0.0001; † 0.0001≥p<0.001; ‡ 0.001>p≥0.01; § 0.01>p≥0.05

Figure 3

Sensitivity analysis of exposure likelihood-matched comparisons of thymoglobulin versus basiliximab across maximum allowable matching differences.

Figure 4

Sensitivity analysis of outcome risk score-matched comparisons of thymoglobulin versus basiliximab across maximum allowable matching differences.