TOLERANCE OF EC-MPS IN COMBINATION WITH CNI IN KIDNEY TRANSPLANT RECIPIENTS - POLISH EXPERIENCE.

CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY

J. Gozdowska, A.L. Urbanowicz, T. Grochowiecki, A. Chmura, M. Durlik
Department Of Transplantation Medicine And Nephrology, Medical University of Warsaw, Warsaw/POLAND

Body: Introduction: Enteric-coated mycophenolate sodium (EC-MPS) was developed to reduce the incidence of GI adverse effects in patients on immunosuppression. Multicenter observational study was designed to evaluate safety profile and drug tolerance in kidney transplant recipients. Methods: 300 kidney recipients (mean age 45.8y) were enrolled during 3y period, to receive EC-MPS: de novo (n=175), switched from azathioprine (AZA) (n=62) or from mycophenolate mofetil (MMF) (n=63), in combination with calcineurin inhibitor. During follow-up patients were evaluated at enrollment (Visit 1) and after 4-6 (Visit 2), 10-14 (Visit 3) and 24-28 (Visit 4) weeks. Drugs dosing/concentrations, serum creatinine (SCr), eGFR (MDRD) were recorded, as well as drug tolerance, patient compliance and physician's evaluation of therapy on 4 point scale (poor, fair, good, excellent). Adverse events [AEs] were also monitored at Visit 2, 3, and 4. General mixed models with binomial/multinomial link function were used to model probabilities of categorical outcome variables. Results: 273 patients have completed the study (91%). Mean daily dose of EC-MPS was lower when combined with tacrolimus, as compared to cyclosporine (951 vs. 1208, respectively). Whole study population:

Excellent tolerance - higher expectancy with tacrolimus than with cyclosporine (odds ratio [OR] 2.12; 95% confidence intervals [CI]: 1.01-4.43) and trend for higher expectancy with lower SCr (OR for 1 mg/dL increase in SCr: 0.99; p=0.06);

Excellent physicians evaluation - higher expectancy with earlier EC-MPS introduction (OR for 4 weeks delay: 0.994; 95% CI: 0.989-0.999) and higher expectancy with higher eGFR (OR for 5 mL/min increase: 1.207 ; 95% CI: 1.123-1.306);

AE were reported in 49 patients (16 cases of serious AEs), most commonly: infections (1 sepsis, 6 CMV), anemia, GI AEs.

De novo:

Excellent tolerance - higher expectancy with tacrolimus than with cyclosporine (OR: 3.14; 95% CI: 1.20-8.22);

Excellent compliance - higher expectancy with higher eGFR (OR for 1 mL/min eGFR increase: 1.04; 95% CI: 1.01-1.07) and trend for higher expectancy in younger recipients (<65y) (OR: 7.25; p=0.07);

Excellent physicians evaluation - higher expectancy with higher eGFR (OR for 1 mL/min increase: 1.041; 95% CI: 1.021-1.064) and trend for higher expectancy with earlier EC-MPS introduction (OR for 4 weeks delay: 0.988; 95% CI: 0.977-0.998).

MMF to EC-MPS:

Excellent tolerance - higher expectancy in younger recipients (<65y) (OR: 888; 95% CI: 1.33-593134) and trend for higher expectancy when combined with tacrolimus (OR: 18.63; p=0.07) as well as trend for higher expectancy with earlier EC-MPS introduction (OR: 1.01; p=0.09);

Excellent physicians evaluation - higher expectancy with lower EC-MPS doses (OR for 360 mg dose increase: 0.397; 95% CI: 0.184-0.782) and with higher eGFR (OR for 5 mL/min increase: 1.417 ; 95% CI: 1.172-1.774).

AZA to EC-MPS:

Excellent compliance - trend for higher expectancy in younger recipients (OR for 1 year younger patient: 0.86; p=0.07);

Conclusions: 1. Younger kidney recipients have better tolerance of EC-MPS. 2. EC-MPS tolerance decreases gradually as renal function deteriorates. 3. Increase in delay of EC-MPS introduction results in worse drug tolerance. 4. EC-MPS has better tolerance when combined with tacrolimus, as compared to cyclosporine.

Disclosure: All authors have declared no conflicts of interest.