Tolerance of enteric-coated mycophenolate sodium in combination with calcineurin inhibitor in kidney transplant recipients: Polish experience.

INTRODUCTION

Enteric-coated mycophenolate sodium (EC-MPS) was developed to reduce the incidence of gastrointestinal adverse effects. This multicenter observational study was designed to evaluate the safety profile and drug tolerance in kidney transplant recipients.

METHODS

Three hundred adult kidney recipients (median age 48 years) were enrolled over 3 years to receive EC-MPS de novo (n=175), as a switch from azathioprine (n=62) or mycophenolate mofetil MMF (n=63); in combination with calcineurin inhibitor. Drug doses, serum creatinine, estimated glomerular filtration rate (eGFR), as well as drug tolerance, patient and physician evaluation of therapy (on a 4-point scale) were recorded at enrollment and followed over 28 weeks. We modeled the probability of the highest level (ie, best result) of the categorical outcome variable.

RESULTS

Two hundred seventy-three patients completed the study (91%). In the pooled study group (1) best drug tolerance was expected more frequently with tacrolimus versus cyclosporine (odds ratio [OR] 2.12, P<.05); (2) best physician evaluation, with earlier EC-MPS introduction (OR for 4-week delay: 0.99, P<.03) and higher eGFR (OR for 5 mL/min increase: 1.21, P<.01). Among the EC-MPS de novo administrations group: (1) best drug tolerance was expected more frequently with coadministered tacrolimus versus cyclosporine (OR 3.14, P<.02); (2) best patient evaluation, with higher eGFR (OR for 1 mL/min increase: 1.04, P<.04); and (3) best physician evaluation, with higher eGFR (OR for 1 mL/min increase: 1.04, P<.001) and earlier EC-MPS introduction (OR for 4-week delay: 0.99, P<.03). In the conversion from MMF to EC-MPS group: (1) best drug tolerance was expected less frequently with coadministered cyclosporine versus tacrolimus (OR 0.05, P<.04) and more frequently with younger recipients (OR .001, P<.04); (2) best physician evaluation was expected more frequently with lower EC-MPS dose (OR for 360-mg dose increase: 0.4, P<.01) and with higher eGFR (OR for 5 mL/min increase: 1.42, P<.002). Adverse events were reported among 49/300 patients (16 serious adverse events).

CONCLUSIONS

EC-MPS was tolerated better by younger kidney recipients, when combined with tacrolimus versus cyclosporine, and when introduced earlier after transplantation. EC-MPS tolerance decreased gradually with renal function deterioration.