MO992RABBIT ANTITHYMOCYTE GLOBULIN (RATG) AS INDUCTION THERAPY IN INDIAN PATIENTS UNDERGOING RENAL TRANSPLANTATION: CLINICAL EXPERIENCE FROM RISE REGISTRY
Authors: Ray Deepak Shankar , Gang Sishir , Mandrekar Aniket 
Published: May 2021

Abstract

Background and Aims
Induction therapy with rabbit anti-thymocyte globulin (rATG) in patients with renal transplantation prevents early graft failure due to immunologic rejection. In India, due to the lack of a robust national transplant registry, limited real-world evidence is available on induction immunosuppression. The RISE study aimed to evaluate the safety and effectiveness of induction immunosuppression using rATG in patients undergoing renal transplantation in India.

Method
In this multicenter, prospective, observational cohort study (CTRI/2017/09/009/009700) adult patients (≥18 years) were included if they were due to have a renal transplant and physicians’ decision to use rATG as an induction therapy was independent of this registry and based on routine clinical practice. Acute rejection and infections over 12 months, graft survival and renal function at the end of 6 and 12 months and safety (adverse events [AEs] and serious AEs [SAEs]) were evaluated over 12 months.

Results
Of the 325 patients enrolled, 314 met the eligibility criteria, 313 patients received at least one dose of rATG (safety population) and 299 patients (evaluable population) received at least one dose of rATG and had no critical protocol deviation (ongoing infection, transplantation date deviation, and ABO incompatibility). Of the 299 donors, 81.3% were live donors and the remaining 18.7% deceased. The mean (SD [standard deviation]) age of participants was 42.8 (11.7) years and 76.3% of patients were men. The cumulative mean (SD) rATG dose was 155.06 (91.12) mg. A total of 23 (7.7%) patients experienced graft rejection; of which 21 (91.3%) patients reported acute rejections; one patient had a hyperacute rejection and another patient had accelerated rejection. These rejections occurred within a median time duration of 0.49 months (range: 0.1 to 7.75 months). The diagnosis of graft rejection was most often done by renal biopsy (n=21, 91.3%; 20 of these patients had acute rejection) and clinical diagnosis in two patients. Cellular rejection was the predominant pathology (n=17, 77.3%), followed by mixed rejection (n=3) and antibody-mediated rejection (n=2). The corresponding mean (SD) time to first graft rejection were 5.45 (1.59) and 10.37 (3.58) months, respectively. The graft survival was 93.3% (n=279) at 6 months and 92.3% (n=276) at 12 months (Figure). The mean (SD) glomerular filtration rate was 64.59 (19.57) and 64.93 (20.26) mL/min/1.73m2 at 6 and 12 months, respectively, suggesting normal post-transplant kidney function. Fifty-three patients (17.7%) reported a total of 74 infections, the most common being bacterial (n=37) followed by viral (n=8) and fungal infections (n=5). Urinary tract infection was the most common site of infection (25 events in 23 patients) followed by sepsis (3 events in 2 patients). A total of 342 AEs were reported in 154 (49.2%) patients during 12 months. The majority of AEs (n=195) were of mild intensity, followed by 124 and 22 events of moderate and severe intensity, respectively. SAEs (n=111) were reported in 56 patients. Pyrexia was the most commonly reported SAE in 10 patients (12 events). A total of seven deaths were reported during the study (acute coronary syndrome, left ventricular dysfunction, neutropenic sepsis, septic shock, sudden sepsis, n=1 each and undetermined, n=2).

Conclusion
The study demonstrated low rejection rate, better survival and function at 6 months and 1 year and an acceptable safety profile of rATG with overall infection incidence less than 18%. Additional follow-up data is warranted to understand factors associated with rejection of graft.
This study was funded by Sanofi, India.