Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients

Abstract

Background and objectives Alemtuzumab is a humanized anti-CD52 monoclonal antibody used as induction in kidney transplantation (KTX) since 2003. Few studies have evaluated long-term outcomes of this agent or changes in outcomes over time.Design, setting, participants, & measurements A retrospective cohort study was performed examining United States registry data from 2003 to 2014 of primary KTX recipients receiving induction with alemtuzumab (AZ; n=5521) or antithymocyte globulin (ATG; n=8504) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil and early withdrawal of steroids. The primary outcome was overall death-censored graft survival (DCGS), and secondary outcomes were overall patient survival and 1-year acute rejection. Multivariate models were fit with donor, recipient, and transplant covariates. Because poorer outcomes with AZ may occur from a learning curve impact with the use of a new medication, transplant year was categorized into three time periods to evaluate outcomes over time (2003-2005, 2006-2008, $2009), and an interaction term of induction type with transplant year category was included in all models to test for era impacts.Results On multivariate analysis of DCGS there was a significant interaction between AZ and era (P,0.001). Risk-adjusted patient survival (aHR, 1.32; 95% CI, 1.08 to 1.61; aHR, 1.26; 95% CI, 1.09 to 1.46; and aHR, 1.10; 95% CI, 0.93 to 1.29 by era, respectively) and acute rejection (adjusted odds ratio [aOR], 1.17; 95% CI, 0.96 to 1.42; aOR, 0.94; 95% CI, 0.82 to 1.07; aOR, 0.89; 95% CI, 0.81 to 0.98 by era, respectively) with AZ was comparable with ATG in the most recent era; however, there was no significant interaction with time (P=0.13 and P=0.06, respectively).Conclusions Current alemtuzumab utilization is associated with comparable graft and patient survival and acute rejection compared with ATG. Graft survival with alemtuzumab has improved over time.

Analysis of Risk Factors for Kidney Retransplant Outcomes Associated with Common Induction Regimens: A Study of over Twelve-Thousand Cases in the United States

“…Consistent with reports favoring the trend of using alemtuzumab induction with steroid-sparing regimens [ 41 , 42 ], our results in Table 1 showed that the alemtuzumab cohort had the lowest percentage of patients on maintenance corticosteroids after retransplant (52% alemtuzumab, 84% ATG, and 90% basiliximab; p < .001), ( Table 1 ). Although steroids use in maintenance immunosuppression was associated with lower risks for acute rejection and death-censored graft loss in the main Cox models ( Figure 2 ), the Cox model with interaction in Figure 6 did not show significant associations between death-censored graft loss and the variable termed: induction agent (ATG and alemtuzumab) × steroid use.…”

“…In a study of kidney transplants between 2006 and 2014, where the transplant recipients studied were on a uniform maintenance immunosuppression consisting of CNI and mycophenolate, Serrano et al found that graft outcomes related to alemtuzumab versus ATG induction improved with time due to a “learning curve” effect [ 42 ]. In our current analysis, while retransplant in the later era (after 2008) was associated with lower risks of death, AR, and death-censored graft loss in the main Cox models ( Figure 2 ), the interaction models showed that these benefits were not induction agent specific (Figures 3 , 4 , and 6 ).…”

Center practice drives variation in choice of US kidney transplant induction therapy: a retrospective analysis of contemporary practice

“…In recipients of living donor transplants who were not treated with steroids, both ALEM and TMG reduced acute rejection risk compared with IL2rAb; however, ALEM has been associated with higher composite risk of graft failure or patient death, while TMG was not . Results with ALEM may improve over time as a center becomes more experienced with the drug .…”

Comparing Outcomes between Antibody Induction Therapies in Kidney Transplantation

“…11 Despite concerns that induction might confer greater risks among elderly patients, our analyses detected no evidence to suggest that basiliximab has substantial advantages among elderly kidney transplant patients. Some observational studies and randomized controlled trials saw no difference in mortality, 21,35,36 allograft failure, 35,36 and/or acute rejection 21,23,[34][35][36] for alemtuzumab and basiliximab recipients relative to rATG recipients.…”

“…23 We acknowledge some emerging evidence that alemtuzumab is associated with lower risk of acute rejection for low-risk patients versus basiliximab or rATG, but similar acute rejection risk to rATG among high-risk patients. 7,21,23,[34][35][36][37][38] Specifically, one randomized controlled trial found that patients who received alemtuzumab had significantly lower 6-month acute rejection risk than patients who received basiliximab. 38 We considered our analysis of acute rejection to be exploratory because of an earlier validation study by our group that acute rejection is reported with variable sensitivity across centers.…”