title: LCPT once-daily extended-release tacrolimus tablets versus twice-daily capsules: a pooled analysis of two phase 3 trials in important de novo and stable kidney transplant recipient subgroups.
abstract: African-American and elderly kidney transplant recipients (KTR) have increased risk for poor clinical outcomes post-transplant. Management of immunosuppression may be challenging in these patients and contribute to worse outcomes. A novel once-daily formulation of tacrolimus (LCPT) has demonstrated noninferiority, similar safety, improved bioavailability, a consistent concentration time profile, and less peak and peak-trough fluctuations vs. tacrolimus twice-daily (Tac BID). This pooled analysis of two phase 3 randomized, controlled trials, including 861 (LCPT N = 428; Tac BID N = 433; 38% of patients were stable KTR, and 62% were de novo KTR) patients, examined the efficacy of LCPT in KTR subgroups (blacks, females, and age ≥65). Overall, treatment failure [death, graft failure, centrally read biopsy-proven acute rejection (BPAR), or lost to follow-up] at 12 months was as follows: LCPT: 11.9%, BID Tac: 13.4% [-1.48% (-5.95%, 2.99%)]. BPAR rates were as follows: LCPT: 8.2%, Tac BID: 9.5% [-1.29% (-5.14%, 2.55%)]. Numerically, fewer treatment failure events with LCPT were found in the majority of subgroups, with significantly less treatment failure associated with LCPT among black KTR [-13.82% (-27.22%, -0.31%)] and KTR ≥65 [-13.46% (-25.27%, -0.78%)]. This pooled analysis suggests numerically lower efficacy failure rates associated with LCPT among high-risk subgroups, in particular black KTR and KTR ≥65 years old.
authors.affiliation: David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Suphamai
authors.initials: S
authors.lastname: Bunnapradist
authors.affiliation: Hôpital de Rangueil/Larrey, Toulouse, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Rostaing
authors.affiliation: University of Cincinnati Medical Center & The Christ Hospital, Cincinnati, OH, USA.
authors.forename: Rita R
authors.initials: RR
authors.lastname: Alloway
authors.affiliation: University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: West-Thielke
authors.affiliation: Henry Ford Health System, Detroit, MI, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Denny
authors.affiliation: St. Barnabas Medical Center, Livingston, NJ, USA.
authors.forename: Shamkant
authors.initials: S
authors.lastname: Mulgaonkar
authors.affiliation: Charité University, Berlin, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
mesh_terms: D000368:Aged; D001706:Biopsy; D003627:Data Interpretation, Statistical; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection / Q000209:etiology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007668:Kidney / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013607:Tablets; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D013607:Tablets; D016559:Tacrolimus
keywords: efficacy; extended-release; immunosuppression; kidney transplantation; tacrolimus