CLINICAL IMMUNOSUPPRESSION - NEW AGENTS

A. Sánchez-fructuoso¹, L. Rostaing², M. Glyda^3
1Department Of Transplantology, Hospital Clínico San Carlos, Madrid/SPAIN, ²Nephrology, Dialysis And Organ Transplant Department, Toulouse University Hospital, Toulouse/FRANCE, ³Department Of Transplantology, Province Hospital, Poznan/POLAND

Body: Introduction: Ciclosporin (CyA) is associated with side effects that may increase cardiovascular risk and non-compliance. This study evaluated the safety of Tacrolimus prolonged-release formulation (Tacrolimus QD) in renal transplant recipients converted from a CyA-based immunosuppressive regimen due to CyA-related side effects. Methods: This 24-week, multicentre, open-label study enrolled stable renal transplant recipients (aged ≥18 years, transplant ≥12 months prior to enrolment) into 4 subgroups defined according to their CyA-related side effect: hyperlipidemia; hypertrichosis/hirsutism; arterial hypertension; gingival hyperplasia. Patients were converted by substitution of CyA with Tacrolimus QD at 0.1 mg/kg/day (morning dosing) with whole-blood trough levels of 5–15 ng/mL for 4 weeks and then 4–10 ng/mL until study end. Concomitant immunosuppressive medication was maintained after conversion. Results: 346 patients were enrolled; 339 patients were evaluable for effects of Tacrolimus QD conversion on CyA side effects: 49 hyperlipidemia, 114 hypertrichosis, 92 arterial hypertension, 84 gingival hyperplasia. There was a rapid reduction in the severity of CyA-related side effects in most patients. The arterial hypertension cohort experienced mean reductions of –5 mmHg diastolic blood pressure and –15 mmHg systolic blood pressure. Mean total cholesterol fell by 0.8 mmol/L (–12%) in the hyperlipidemic cohort. Creatinine clearance remained unchanged in all 4 subgroups. Overall, 65% experienced AEs with similar frequencies across all subgroups (Table), of which 36% were treatment-related. Serious AEs were reported in 14% of patients, 5% were treatment-related. Three cases of new-onset diabetes requiring insulin occurred during the study. AEs leading to withdrawal were low (3%–10%); GI disorder accounted for 6 of all 16 cases, with the remaining cases being diverse in nature. There were no patient deaths or graft losses during the study; 1 death (lymphoma complications) and 1 graft failure occurred after study withdrawal. Conclusions: Conversion to Tacrolimus QD from CyA resulted in rapid resolution of CyA side effects and was well tolerated without rejection or negative effects on renal function.

Disclosure: All authors have declared no conflicts of interest.