Long-term safety and efficacy of antithymocyte globulin induction: use of integrated national registry data to achieve ten-year follow-up of 10-10 Study participants.
BACKGROUND
Rabbit antithymocyte globulin (rATG, Thymoglobulin®) is the most common induction immunosuppression therapy in kidney transplantation. We applied a database integration strategy to capture and compare long-term (10-year) outcome data for US participants in a clinical trial of rATG versus FDA-approved basiliximab.


METHODS
Records for US participants in an international, 1-year, randomized clinical trial comparing rATG and basiliximab induction in deceased donor kidney transplantation were integrated with records from the US national Organ Procurement and Transplantation (OPTN) registry using center, transplant dates, recipient sex, and birthdates. The OPTN captures center-reported acute rejection, graft failure, death, and cancer events, and incorporates comprehensive death records from the Social Security Death Master File. Ten-year outcomes according to randomized induction regimen were compared by Kaplan-Meier analysis (two-sided P). Non-inferiority of rATG was assessed using a one-tailed equivalence test (a-priori equivalence margins of 0-10 %).


RESULTS
Of 183 US trial participants, 89 % (n = 163) matched OPTN records exactly; the remainder were matched by extending agreement windows for transplant and birthdates. Matches were validated by donor and recipient blood types. By Kaplan-Meier analysis, 10 years post-transplant, freedom from acute rejection, graft failure, or death was 32.6 % and 24.0 % in the rATG and basiliximab arms, respectively (P = 0.09). The incidence of acute rejection with rATG versus basiliximab induction was 21.0 % versus 32.8 % (P = 0.07). Patient survival (52.8 % [Corrected] versus 52.2 %, P = 0.92) and graft survival (34.3 % versus 30.9 %, P = 0.56) rates were numerically and statistically similar for both arms. Comparison of the composite outcome meets non-inferiority criteria even with a 0 % equivalence margin (one-sided P = 0.04). With a 10 % equivalence margin, the odds that rATG is no worse than basiliximab for 10-year risk of the composite endpoint are >99 %.


CONCLUSIONS
Ten years post-transplant, rATG induction has comparable efficacy and safety to FDA-approved basiliximab. Integration of clinical trial records with national registry data can enable long-term monitoring of trial participants in transplantation, circumventing logistical and cost barriers of extended follow-up.


BACKGROUND
ClinicalTrials.gov NCT00235300.
Center for Outcomes Research, Saint Louis University School of Medicine, St. Louis, MO, USA. lentinek@slu.edu.|Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO, USA. lentinek@slu.edu.|Saint Louis University, Salus Center 4th Floor, 3545 Lafayette Avenue, St. Louis, MO, 63104, USA. lentinek@slu.edu.
Krista L
KL
Lentine
Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO, USA. schnitm@slu.edu.
Mark A
MA
Schnitzler
Center for Outcomes Research, Saint Louis University School of Medicine, St. Louis, MO, USA. xiaoh@slu.edu.|Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO, USA. xiaoh@slu.edu.
Huiling
H
Xiao
Transplant Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. dbrennan@dom.wustl.edu.
Daniel C
DC
Brennan
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000077552:Basiliximab; D057286:Electronic Health Records; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007518:Isoantibodies / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D008297:Male; D008498:Medical Record Linkage; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced / Q000276:immunology; D016017:Odds Ratio; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D012042:Registries; D012307:Risk Factors; D013997:Time Factors; D009927:Tissue and Organ Procurement; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D011993:Recombinant Fusion Proteins; C035678:anti-Thy antibody; D000077552:Basiliximab