Despite adverse effects like
hyperglycemia, new-onset diabetes after transplant (NODAT), and infectious complications,
corticosteroid use remains an important part of
liver transplantation (LT) immune suppression.
Budesonide, a synthetic
corticosteroid, undergoes extensive first-pass hepatic metabolism with only 10% systemic bioavailability, providing an opportunity for an improved toxicity-therapeutic ratio. Although effective in the treatment of
autoimmune hepatitis, the effects of
budesonide for LT immune suppression are unknown. We conducted a single-center phase 2a trial to study the safety and efficacy of
budesonide immunosuppressive therapy. From July 2017 to November 2018, 20 patients undergoing a first LT received
budesonide tapering doses (from 9 to 3 mg) for 12 weeks. Patients were compared with matched control patients who received
prednisone from the same time period. Additionally, both groups received
calcineurin inhibitors and
mycophenolate mofetil. Outcome measures at week 24 included rates of biopsy-proven acute cellular rejection (ACR), NODAT (
hemoglobin A1c >6.4%), and infectious complications. In the
budesonide arm, 1 patient developed ACR at week 5 and was removed from the study. Another patient stopped the study
drug at week 8 due to persistent
nausea. Rates of ACR were similar between the
budesonide and control groups (5% versus 5%, P = 1.00). Three patients in the control group developed NODAT versus none in the
budesonide group (15% versus 0%; P = 0.23). There were 6
infections in the control group compared with none in the
budesonide group (30% versus 0; P = 0.02). These pilot data suggest that
budesonide has the potential to be a safe and effective alternative to
prednisone for LT immune suppression while reducing
steroid-induced
infections and NODAT. Randomized controlled trials are required to validate these findings.