Abstract: ADHERE was a randomized, open-label, Phase IV study comparing renal
function at Week 52 postkidney transplant, in patients who received prolongedrelease
tacrolimus-based immunosuppressive regimens. On Days 0?27, patients
received prolonged-release tacrolimus (initially 0.2 mg/kg/day), corticosteroids,
and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to
receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolongedrelease
tacrolimus (?25% dose reduction on Day 42) plus sirolimus (Arm 2).
The primary endpoint was glomerular filtration rate by iohexol clearance
(mGFR) at Week 52. Secondary endpoints included eGFR, creatinine clearance
(CrCl), efficacy failure (patient withdrawal or graft loss), and patient/graft
survival. Tolerability was analyzed. The full-analysis set comprised 569 patients
(Arm 1: 287; Arm 2: 282). Week 52 mean mGFR was similar in Arm 1 versus
Arm 2 (40.73 vs. 41.75 ml/min/1.73 m2; P = 0.405), as were the secondary endpoints,
except composite efficacy failure, which was higher in Arm 2 versus 1
(18.2% vs. 11.5%; P = 0.002) owing to a higher postrandomization withdrawal
rate due to adverse events (AEs) (14.4% vs. 5.2%). Results from this study show
comparable renal function between arms at Week 52, with fewer AEs leading to
study discontinuation with prolonged-release tacrolimus plus MMF (Arm 1)
versus lower dose prolonged-release tacrolimus plus sirolimus (Arm 2).