Efficacy and safety of enteric-coated mycophenolate sodium in de novo renal transplant recipients: pooled data from three 12-month multicenter, open-label, prospective studies.
BACKGROUND
The myfortic Prospective Multicenter Study (myPROMS) utilizes a core protocol in which renal transplant patients receive enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine microemulsion. Substudies investigate specific aspects of the immunosuppressive regimen.


METHODS
A pooled analysis of three 12-month myPROMS substudies in de novo renal transplant patients was undertaken. Patients in the US01 and DE01 substudies were randomized to higher or lower cyclosporine C(2) target ranges; patients in FR01 were randomized to early or delayed introduction of cyclosporine. All patients received steroids and interleukin-2 receptor antagonist induction.


RESULTS
In total, 456 patients were included in the pooled analysis. Treatment failure (biopsy-proven acute rejection, graft loss, or death) occurred in 118 patients (25.9%) by month 12, with biopsy-proven acute rejection reported in 101 patients (22.1%). Fourteen patients (3.1%) lost their graft, and six patients died (1.3%). Median calculated creatinine clearance was 62.9 mL/min at month 12 (median serum creatinine, 138 +/- 51 mumol/L). Gastrointestinal (GI) adverse events were reported in 354 patients (77.6%); these were mild or moderate in 323 patients. Within 12 months, 16.2% of patients required EC-MPS dose changes for GI adverse events. GI disorders led to EC-MPS discontinuation in only 10 patients (2.2%). Over the 12-month study, mean EC-MPS dose was 1352 +/- 230 mg/d (94% of recommended dose).


CONCLUSIONS
Cyclosporine, EC-MPS, and steroids with interleukin-2 antagonist induction offers effective and well-tolerated immunosuppression following renal transplantation. Graft survival was excellent and renal function was stable. High EC-MPS dosing was sustained throughout (>90% recommended dose) and dose modifications due to EC-MPS-related adverse events or infections were infrequent.
Legendre
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Service de Nephrologie et Transplantation, Hôpital Necker, Bâtiment Sevres, 161 rue de Sevres, Paris F-75015, France. christophe.legendre@nck.ap-hop-paris.fr
Cohen
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Zeier
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M
Rostaing
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Budde
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D000328:Adult; D002102:Cadaver; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018579:Patient Selection; D044469:Racial Groups; D012449:Safety; D013608:Tablets, Enteric-Coated; D014019:Tissue Donors; D017211:Treatment Failure; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D009173:Mycophenolic Acid