ABSTRACT
Purpose: Rabbit anti-thymocyte globulin (rATG) is a polyclonal antibody utilized for induction immunosuppression in high immunologic risk kidney transplant recipients. However, the optimal total dose of rATG has not been identified. Higher cumulative doses of rATG may be associated with an increased risk of adverse infectious and hematologic outcomes, while lower cumulative doses may not provide adequate immunosuppression to prevent acute rejection. In March 2020, the total rATG dose in our institution's induction protocol for kidney transplant recipients was reduced from 6 mg/kg to 4.5 mg/kg to avoid potential infectious complications from COVID- 19. The objective of this study is to compare the efficacy and safety between two different doses of rATG. Method(s): This was a single center, retrospective chart review of adult kidney transplant recipients who received rATG for induction between September 1, 2019 and August 31, 2020. Patients who received a total dose of 6 mg/kg rATG were compared to patients who received a total dose of 4.5 mg/kg. The primary outcome was biopsy proven acute rejection (BPAR) within 90 days of transplant. Secondary outcomes assessed incidence of infection, leukopenia, neutropenia, thrombocytopenia, and delayed graft function within 90 days of transplant. Result(s): Eighty-one adult kidney transplant recipients were included in this study;37 received 6 mg/kg of rATG and 44 received 4.5 mg/kg of rATG. Incidence of BPAR was significantly lower in the 6 mg/kg rATG group compared to the 4.5 mg/ kg group (2.7% vs 20.5%, p=0.02). The majority of rejection episodes were classified as borderline. Patients who had BPAR were treated with corticosteroids. The number of patients who had an infection was significantly lower in the 6 mg/kg group compared to 4.5 mg/kg group (21.6% vs 47.7%, p=0.02). There was a numerically lower incidence of delayed graft function in the 6 mg/kg group compared to the 4.5 mg/kg group (25.0% vs 43.2%, p=0.18). Incidence of leukopenia, neutropenia, and thrombocytopenia were similar between groups. Conclusion(s): In conclusion, a lower cumulative dose of rATG was associated with an increased risk of borderline rejection and a numerically higher incidence of delayed graft function.
ABSTRACT
Rationale Severe acute respiratory syndrome coronavirus 2 can cause an uncontrolled release of proinflammatory cytokines, such as interleukin-6 (IL-6), leading to cytokine release syndrome. Tocilizumab, a humanized monoclonal antibody that inhibits the IL-6 receptor, has been proposed as a treatment option to prevent clinical worsening in coronavirus disease 2019 (Covid-19). There is limited data regarding the safety of using tocilizumab in patients with Covid-19. The objective of this study was to evaluate the pneumonia at University Hospitals Cleveland Medical Center. Methods This was an institutional review board approved, singlecenter, retrospective chart review of all patients who received tocilizumab for Covid-19 between March 1, 2020 and October 31, 2020. Patients less than 18 years old were excluded. The primary outcome was incidence of secondary infection within 28 days or until end of hospitalization. Secondary outcomes included incidence of adverse events, length of stay in the intensive care unit, length of hospitalization, progression to invasive mechanical ventilation, duration of mechanical ventilation, and death. Results There were eighteen patients who received tocilizumab for the treatment of Covid-19. Within the first 28 days after receiving tocilizumab, nine (50%) patients developed a secondary infection and ten (55.6%) patients were given antibiotics. Liver enzyme elevations also occurred in nine (50%) of the patients who received tocilizumab. At 28 days, seven (38.9%) patients were discharged from the hospital, four (22.2%) were mechanically ventilated, two (11.1%) were receiving oxygen via nasal cannula, and five (27.8%) were dead. Median ICU and hospital length of stay were 10.5 and 14 days, respectively. Five (27.8%) patients received a second dose of tocilizumab and all five patients were alive at 28 days after receiving first dose of tocilizumab. Conclusion In this retrospective chart review of patients with Covid-19 who received tocilizumab as part of their management, half developed secondary infections and half developed transient liver enzyme elevations. These adverse events may be associated with the use of tocilizumab in these patients. As of now, there is a lack of consensus on the role of tocilizumab in the treatment of Covid-19.