The appropriate dose of thymoglobulin induction therapy in kidney transplantation

Clin Transplant. 2017 Jun;31(6) doi: 10.1111/ctr.12977.
Abstract
BACKGROUND:

Thymoglobulin is used effectively as an induction agent in kidney transplantation, but there is no consensus on the optimal dose. In order to delineate the safest effective dose, an open-labeled randomized clinical trial was designed.

METHODS:

In this study, 90 adult kidney transplant recipients (KTR) were randomized before transplantation in three groups to receive thymoglobulin: Arm A (4.5 mg/kg in 3 days), Arm B (4.5 mg/kg single bolus dose), and Arm C (6 mg/kg in 3 days). Renal function, infections, and rate of readmissions were evaluated during the first post transplantation year.

RESULTS:

Ninety adult kidney recipients were enrolled (51% deceased donor). No significant statistical difference was found in acute rejection episodes or type of rejection between these groups, although patients in Arm A showed more severe histopathologic changes according to Banff 2013 criteria, in renal biopsies (P=.03). At the first month after transplantation serum Cr was lower (P=.001) and GFR was higher (P=.04) in Arm A, but there was no significant difference among the three groups at 3, 6, and 12 months post-transplant.

CONCLUSION:

Although all regimens showed the same efficacy regarding the rate of rejection episodes, 3-day 4.5 mg/kg Thymoglobulin had significantly fewer complications.

Expert Review
Reviewer: Professor Rita R. Alloway, Transplant Clinical Research, University of Cincinnati, College of Medicine, USA.
Conflicts of Interest: I am on the Sanofi/Genzyme speakers bureau and I served as a consultant on the Sanofi/Genzyme FDA submission.
Clinical Impact Rating 1
Review: This 90 patient randomized kidney transplant study by Nafar et al compared three different Thymoglobulin induction-dosing regimens of 4.5mg/kg over 3 days (Arm A), 4.5mg/kg as a single bolus, and 6mg/kg over 3 days (Arm C). The primary endpoint of incidence of rate and severity of biopsy proven acute rejection (BPAR) was low (2 per group) and not statistically different. Study results should be interpreted with caution due to 1) the sample size is inadequate to assess the endpoint, 2)16% and 10% of patients in Arm B and C respectively did not receive full randomized dose, and 3) the author acknowledged, the BPAR rate was limited by patients unwillingness to undergo biopsy. Recently Thymoglobulin was FDA approved for prophylaxis of acute rejection in patients receiving a kidney transplant at a dose of 1.5mg/kg administered daily for 4-7 days. This dose was based upon two historical randomized trials and extensive safety information. While this dose range is efficacious and safe, further refinements in Thymoglobulin dosing based upon 1) immunologic risk, 2) safety factors, 3) dosing factors (i.e. ideal body weight, actual body weight, dose maximum, etc.) and 4) concomitant immunosuppression, are desirable to individualize immunosuppression. While this study attempts to assess the impact of lower Thymoglobulin induction doses, these results are not generalizable. Appropriately, controlled and powered dose finding studies would be required.
Methodological quality
Jadad score 2
Allocation concealment YES
Data analysis INTENTION TO TREAT
Metadata
Funding: Funding not described
Publication type: Randomized Controlled Trial, Randomised Controlled Trial
Trial registration: ISRCTN - 17364752
Organ: Kidney
Language: English
Author email: nooshindalili4@gmail.com
MeSH terms: Antilymphocyte Serum; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Prognosis; Remission Induction; Risk Factors; 0 (Antilymphocyte Serum); 0 (Immunosuppressive Agents); D7RD81HE4W (Thymoglobulin)