Effects of mycophenolate mofetil introduction in liver transplant patients: results from an observational, non‐interventional, multicenter study (LOBSTER)

Abstract

The benefits of calcineurin inhibitor (CNI)-sparing regimens on renal function following liver transplantation (LT) have been demonstrated in clinical studies. This observational study assessed the real-life effects of mycophenolate mofetil (MMF) introduction in LT patients. Four hundred and ninety-seven patients in whom MMF was introduced according to local standards or clinical considerations were entered. Patients were grouped by time between transplantation and start of MMF (start of study): Group A (n = 263): ≤6 d; Group B (n = 64): >6 d to ≤1 month; Group C (n = 74): >1 month to ≤1 yr; and Group D (n = 96): >1 yr. CNI sparing occurred in all groups, particularly in Groups C and D. Mean MMF doses at 12 months were 1202.7, 1363.5, 1504.7, and 1578.1 mg/d, respectively, in Groups A-D. At introduction of MMF, median glomerular filtration rate was 73.3, 81.7, 62.7, and 53.7 mL/min/1.73 m(2) in Groups A-D. At 12 months, this decreased to 66 mL/min/1.73 m(2) in Groups A and B, remained stable in Group C, and increased in Group D (64.8 mL/min/1.73 m(2) ). Serious adverse drug reactions were lowest in Group D. In conclusion, MMF with a subsequent decrease in CNI was well tolerated and improved renal function even years after transplantation. A more forceful MMF dosing strategy with greater CNI sparing may further improve renal function.

Protecting the Kidney in Liver Transplant Recipients: Practicee-Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice

“…There was significant improvement in eGFR over a 1 year follow-up period in the MMF and low dose CNI arm, without episodes of rejection. Furthermore, two other observational studies demonstrated significant GFR increases with conversion from standard CNI to reduced-dose CNI + MMF without adverse events (67, 70). The main benefit of this CNI reduction strategy was seen in applying this regimen within 1–2 years of LT.…”

“…Despite evidence of using mTOR-I and MMF early after LT to minimize CNI nephrotoxicity, this strategy does not seem to equally apply later after LT (63–70). The trials examining these proposed renal sparing regimens to date are either prospective uncontrolled trials, controlled trials with small sample sizes or retrospective observational studies.…”

“…Renal protection late (>12 months) after LT Despite evidence of using mTOR-Is and MMF early after LT to minimize CNI nephrotoxicity, this strategy does not seem to apply as well later after LT (62)(63)(64)(65)(66)(67)(68)(69) (62). There was significant improvement in eGFR over a 1-year follow-up period in the MMF and low-dose CNI arm, without episodes of rejection.…”

“…Finally, a recent systematic review summarized the data on complete CNI withdrawal in favor of MMF in regard to renal dysfunction (71). Five trials reported significantly higher risks of AR (relative risk 4.96, 95% confidence interval 1.75-14), without graft loss or death, following full MMF conversion (67,69,(71)(72)(73). However, GFR improved by a mean of 8.3 mL/min for those given MMF in combination with CNI reduction or elimination, even with GFR < 30 mL/min.…”

Abdominalchirurgie trifft Nephrologie: Wichtige nephrologische Aspekte vor und nach Nieren- bzw. Lebertransplantation

“…Ein Wechsel der Immunsuppression von einem CNI-basierten Schema zu mTOR-Inhibitoren (Sirolimus, Everolimus) oder Mycophenolat-Mofetil (MMF) scheint zu einer Verbesserung der Nierenfunktion zu führen und wird aktuell in klinischen Studien untersucht (z. B. HEPHAISTOS-Studie, ClinicalTrials.gov Identifier: NCT01551212) [57,58].…”