Randomized Trial of Three Induction Antibodies in Kidney Transplantation

Ciancio, Gaetano; Gaynor, Jeffrey J.; Guerra, Giselle; Sageshima, Junichiro; Chen, Linda; Mattiazzi, Adela; Roth, David; Kupin, Warren; Tueros, Lissett; Flores, Sandra; Hanson, Lois; Vianna, Rodrigo; Burke, George W.

doi:10.1097/01.tp.0000441089.39840.66

Cited by 35 publications

(31 citation statements)

References 58 publications

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“…The prospective randomized trial that showed higher BPAR and lower graft survival in the AZ arm had minimized tacrolimus and mycophenolate mofetil only among those receiving AZ (14). In fact, through subset analysis, the authors found that the significantly poorer renal function observed in the AZ group was specifically a result of early underimmunosuppression of maintenance agents (14).…”

Section: Discussionmentioning

confidence: 90%

“…A large retrospective analysis also found lower acute rejection rates and better early graft survival when full doses of tacrolimus and mycophenolate mofetil were administered in the context of steroid avoidance or early withdrawal (13); however, others have not (17). The prospective randomized trial that showed higher BPAR and lower graft survival in the AZ arm had minimized tacrolimus and mycophenolate mofetil only among those receiving AZ (14). In fact, through subset analysis, the authors found that the significantly poorer renal function observed in the AZ group was specifically a result of early underimmunosuppression of maintenance agents (14).…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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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“…Early attempts at steroid withdrawal were associated with high rejection rates and early graft failures (22)(23)(24). This trend changed with the incorporation of antibody induction into the protocols (25)(26)(27)(28). In the context of no steroid protocols, the current KDIGO guidelines recommend using a lymphocyte-depleting agent rather than an IL2-RA for kidney transplant recipients at higher risk for rejection (2B equals a moderate level of evidence).…”

Section: Steroid Avoidancementioning

confidence: 99%

Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate

Tanrıöver

Jaikaransingh

MacConmara³

et al. 2016

CJASN

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Background and objectives IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent for induction therapy in renal transplantation. However, this remains controversial in deceased donor renal transplantation (DDRT) maintained on tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids.Design, setting, participants, & measurements We studied the United Network for Organ Sharing Registry for patients receiving DDRT from 2000 to 2012 maintained on TAC/MPA at transplantation hospital discharge (n=74,627) to compare outcomes of IL2-RA and other induction agents. We initially divided the cohort into two groups on the basis of steroid use at the time of discharge: steroid (n=59,010) versus no steroid (n=15,617). Each group was stratified into induction categories: IL2-RA, rabbit antithymocyte globulin (r-ATG), alemtuzumab, and no induction. The main outcomes were incidence of acute rejection within the first year and overall graft failure (defined as graft failure and/or death) post-transplantation. Propensity score (PS), specifically inverse probability of treatment weight, analysis was used to minimize selection bias caused by nonrandom assignment of induction therapies.Results Median (25th, 75th percentiles) follow-up times were 3.9 (1.1, 5.9) and 3.2 (1.1, 4.9) years for steroid and no steroid groups, respectively. Acute rejection within the first year and overall graft failure within 5 years of transplantation were more common in the no induction category (13.3%; P,0.001 and 28%; P=0.01, respectively) in the steroid group and the IL2-RA category (11.1%; P=0.16 and 27.4%; P,0.001, respectively) in the no steroid group. Compared with IL2-RA, PS-weighted and covariate-adjusted multivariable logistic and Cox analyses showed that outcomes in the steroid group were similar among induction categories, except that acute rejection was significantly lower with r-ATG (odds ratio [OR], 0.68; 95% confidence interval [95% CI], 0.62 to 0.74). In the no steroid group, compared with IL2-RA, odds of acute rejection with r-ATG (OR, 0.80; 95% CI, 0.60 to 1.00) and alemtuzumab (OR, 0.68; 95% CI, 0.53 to 0.88) were lower, and r-ATG was associated with better graft survival (hazard ratio, 0.86; 95% CI, 0.75 to 0.99).Conclusions In DDRT, compared with IL2-RA induction, no induction was associated with similar outcomes when TAC/MPA/steroids were used. r-ATG seems to offer better graft survival over IL2-RA in steroid avoidance protocols.

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“…Most are case reports describing alemtuzumab as salvage or induction therapy. 123,163,[166][167][168][169][170][171][172][173][174][175][176] In a small group of lung transplant recipients with rejection refractory to steroids and ATG, alemtuzumab appeared to be effective in reversing rejection and bronchiolitis obliterans syndrome. 177 Treatment of rejection appears similarly effective in kidney transplant recipients but may be associated with increased early infection-related deaths.…”

Section: Alemtuzumab (Campath)mentioning

confidence: 99%

Antibody-Mediated Rejection in Cardiac Transplantation: Emerging Knowledge in Diagnosis and Management

Colvin¹,

Cook²,

Chang³

et al. 2015

Circulation

273

248

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Randomized Trial of Three Induction Antibodies in Kidney Transplantation

Abstract: Long-term results clearly indicate inferior clinical outcomes in group B.

Cited by 35 publications

References 58 publications

Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients

Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients

Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate

Antibody-Mediated Rejection in Cardiac Transplantation: Emerging Knowledge in Diagnosis and Management

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