Kidney Transplantation With Minimized Maintenance: Alemtuzumab Induction With Tacrolimus Monotherapy—An Open Label, Randomized Trial

Chan, Kakit; Taube, David; Roufosse, Candice; Cook, Terence; Brookes, Paul; Goodall, Dawn; Galliford, Jack; Cairns, Tom; Dorling, Anthony; Duncan, Neill; Hakim, Nadey; Palmer, Andrew J.; Papalois, Vassilios; Warrens, Anthony N.; Willicombe, Michelle; McLean, A.G.

doi:10.1097/tp.0b013e31822ca7ca

Cited by 51 publications

(42 citation statements)

References 26 publications

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“…Over the last decade, alemtuzumab (AZ) (Campath-1 H) has been used in kidney transplant immunosuppressive protocols at a number of centers (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Various single and multicenter studies, both randomized and nonrandomized, are reasonably consistent in demonstrating the effectiveness of AZ as an induction or preconditioning agent in renal transplant recipients usually in the context of steroid avoidance or early withdrawal.…”

Section: Introductionmentioning

confidence: 99%

“…Whereas successes with early steroid withdrawal have been limited by the risk of acute rejection and the perceived or actual reduction of longterm outcomes, some recent trials have been published with encouraging results with early graft survival and acute rejection incidence similar to steroid-based protocols, especially when concomitant antibody induction is administered (1), dosages of cyclosporine are high (2,3), or maintenance therapy consists of tacrolimus and/ or mycophenolate mofetil (4,5).…”

Section: Introductionmentioning

confidence: 99%

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Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients

Serrano

Friedmann

Ahsanuddin

et al. 2015

Clinical Journal of the American Society of Nephrology

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients

Serrano

Friedmann

Ahsanuddin

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…All patients received monoclonal antibody induction with either alemtuzumab (Campath-1H; Cambridge, MA) 30 mg perioperatively, daclizumab (Zenax; Roche, Inc., NJ) 2 mg/kg on days 0 and 14 or basiliximab (Simulect; Novartis Pharma Corp, NJ) 20 mg on days 0 and 4, as described previously (26). Maintenance immunosuppression in the alemtuzumab group consisted of tacrolimus (FK) monotherapy.…”

Section: Immunosuppressionmentioning

confidence: 99%

Acute Cellular Rejection

Willicombe

Roufosse²,

Brookes³

et al. 2014

Transplantation

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“…However, there appears to be a trend towards lower acute rejection rates in groups using alemtuzumab induction [66,67,[73][74][75][76][77] , particularly in association with tacrolimus maintenance therapy. The choice of calcineurin-inhibitor is also important when using monoclonal antibody for induction as acute rejections are temporally delayed [73,78,79] .…”

Section: Alemtuzuamb In Renal Transplantationmentioning

confidence: 99%

Immunomodulator alemtuzumab therapy in kidney transplantation

2016

Macrophage

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Owing to an insufficient understanding of molecular mechanisms, currently the best treatment available for chronic kidney failure is transplantation. There is a heightened need for effective immunosuppressants to counteract rejection. Alemtuzumab, a humanized anti-CD52 antibody, is a powerful lymphocyte-depleting agent. Recently, it has been increasingly used as induction therapy in renal transplantation but its role is not yet fully defined. Indications that early withdrawal of corticosteroids in kidney transplant patients is associated with a better prognosis, has necessitated a hunt for an effective induction agent that supports early corticosteroid withdrawal. In this regard, alemtuzumab is an attractive agent because of its prolonged lymphocyte depleting properties. Long-term studies in kidney transplant patients are still needed for it to be considered as an effective induction agent. Trends in lower acute rejection rates in groups using alemtuzumab induction, particularly in association with tacrolimus maintenance therapy, have been noted and acute rejections were not as severe. Lymphocyte depletion is expected to be associated with an increased incidence of infection and any new immunosuppressive agents should be observed closely for development of infection. Initial studies have not established increased infection rates with alemtuzumab induction, possibly because of the preservation of function of the remaining T-lymphocytes other than CD4+ cells. Further randomized control trials with larger populations are needed to draft a protocol for alemtuzumab's more effective use in transplantation.

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Kidney Transplantation With Minimized Maintenance: Alemtuzumab Induction With Tacrolimus Monotherapy—An Open Label, Randomized Trial

Abstract: Alemtuzumab induction with tacrolimus maintenance monotherapy and short-course steroid use provides a simple, safe, and effective immunosuppressive regimen for renal transplantation.

Cited by 51 publications

References 26 publications

Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients

Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients

Acute Cellular Rejection

Immunomodulator alemtuzumab therapy in kidney transplantation

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