| Popis: |
Background: Despite adverse effects including hyperglycemia, New Onset Diabetes After Transplant (NODAT) and increased rate of infections, corticosteroids remain an important part of liver transplant (LT) immune suppression. Budesonide, a synthetic corticosteroid, undergoes extensive first-pass hepatic metabolism after oral intake with only 10% systemic bioavailability, raising the question of improved toxic-therapeutic ratio. Multiple studies have shown its efficacy in the treatment of immune mediated liver conditions such as primary biliary cholangitis and autoimmune hepatitis while having minimal adverse effects likely due to its limited systemic bioavailability. However, data is scarce regarding use of Budesonide for LT immune suppression.Methods: We conducted a prospective, phase 2a pilot trial to study the safety and efficacy of Budesonide in place of prednisone among LT recipients. During August 2017-November 2018, 20 subjects undergoing first LT with no baseline history of Diabetes Mellitus (DM) were enrolled to receive tapering dose (9 mg to 6 mg to 3 mg) of Budesonide in place of prednisone for the first 12 weeks. All subjects also received a calcineurin inhibitor and mycophenolate. Subjects were compared to matched controls that received prednisone. Outcome measures included rates of Acute Cellular Rejection (ACR, biopsy proven), NODAT (Hemoglobin A1C > 6.4 at week 24) and infections in the first 24 weeks. Outcomes were compared using Fisher’s exact testResults: In the Budesonide arm, one subject developed biopsy proven ACR at week 6, was removed from the trial and received treatment for ACR (intravenous corticosteroids) with good response. Another subject stopped the study drug at week 8 due to persistent nausea. Overall rates of ACR were similar between both groups (5% vs 5%, p=1.000). Three patients in the control group developed NODAT vs none in Budesonide group (15% vs 0%, p=0.231). There were six infections in the control group (Cytomegalovirus (CMV), bacteremia, and fungal infections) as compared to none in the study group (30% vs 0, p=0.020)Conclusion: These pilot data suggests 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. Further multicenter prospective trials are needed to validate these findings and to explore different ways Budesonide can be incorporated into LT immune suppression. |
