title: Efficacy and Safety of Everolimus Plus Low-Dose Tacrolimus Versus Mycophenolate Mofetil Plus Standard-Dose Tacrolimus in De Novo Renal Transplant Recipients: 12-Month Data.
abstract: In this 12-month, multicenter, randomized, open-label, noninferiority study, de novo renal transplant recipients (RTxRs) were randomized (1:1) to receive everolimus plus low-dose tacrolimus (EVR+LTac) or mycophenolate mofetil plus standard-dose Tac (MMF+STac) with induction therapy (basiliximab or rabbit anti-thymocyte globulin). Noninferiority of composite efficacy failure rate (treated biopsy-proven acute rejection [tBPAR]/graft loss/death/loss to follow-up) in EVR+LTac versus MMF+STac was missed by 1.4%, considering the noninferiority margin of 10% (24.6% vs. 20.4%; 4.2% [-3.0, 11.4]). Incidence of tBPAR (19.1% vs. 11.2%; p < 0.05) was significantly higher, while graft loss (1.3% vs. 3.9%; p < 0.05) and composite of graft loss/death/lost to follow-up (6.1% vs. 10.5%, p = 0.05) were significantly lower in EVR+LTac versus MMF+STac groups, respectively. Mean estimated glomerular filtration rate was similar between EVR+LTac and MMF+STac groups (63.1 [22.0] vs. 63.1 [19.5] mL/min/1.73 m2) and safety was comparable. In conclusion, EVR+LTac missed noninferiority versus MMF+STac based on the 10% noninferiority margin. Further studies evaluating optimal immunosuppression for improved efficacy will guide appropriate dosing and target levels of EVR and LTac in RTxRs.
authors: University of Southern California, Los Angeles, CA.
authors: Y
authors: Y
authors: Qazi
authors: Division of Kidney and Pancreas Transplantation, Vanderbilt University Medical Center, Nashville, TN.
authors: D
authors: D
authors: Shaffer
authors: Department of Medicine, Mayo Clinic Arizona, Phoenix, AZ.
authors: B
authors: B
authors: Kaplan
authors: Henry Ford Hospital, Detroit, MI.
authors: D Y
authors: DY
authors: Kim
authors: Universtiy of Michigan, Ann Arbor, MI.|Barnabas Health, Livingston, NJ.
authors: F L
authors: FL
authors: Luan
authors: California Pacific Medical Center, San Francisco, CA.
authors: V R
authors: VR
authors: Peddi
authors: University of Utah School of Medicine, Salt Lake City, UT.
authors: F
authors: F
authors: Shihab
authors: University of California, San Francisco, CA.
authors: S
authors: S
authors: Tomlanovich
authors: University Calgary, Calgary, Alberta, Canada.
authors: S
authors: S
authors: Yilmaz
authors: Novartis Pharmaceuticals Corporation, East Hanover, NJ.
authors: K
authors: K
authors: McCague
authors: Novartis Pharmaceuticals Corporation, East Hanover, NJ.
authors: D
authors: D
authors: Patel
authors: Barnabas Health, Livingston, NJ.
authors: S
authors: S
authors: Mulgaonkar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000074099:Equivalence Trials as Topic; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000627:therapeutic use*; D011183:Postoperative Complications; D011379:Prognosis; D012307:Risk Factors; D012449:Safety; D016559:Tacrolimus / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: antiproliferative agent: mycophenolate mofetil (MMF); calcineurin inhibitor: tacrolimus; clinical research/practice; immunosuppressant; immunosuppressive regimens; kidney transplantation/nephrology; mechanistic target of rapamycin: everolimus; minimization/withdrawal