Does bioequivalence between modified cyclosporine formulations translate into equal outcomes?

Area of Science:

• Nephrology
• Immunology
• Pharmacology

Background:

• Neoral, a brand-name cyclosporine formulation, was replaced by a generic version, Gengraf, on the hospital formulary.
• Cyclosporine is a critical immunosuppressant medication used in organ transplantation.

Purpose of the Study:

• To compare the clinical outcomes of de novo kidney transplant recipients treated with Gengraf versus Neoral.
• To assess the impact of different cyclosporine formulations on acute rejection episodes and drug concentration variability.

Main Methods:

• Single-center, retrospective review of de novo kidney transplant recipients.
• Comparison of outcomes between patients receiving Gengraf (n=88) and Neoral (n=100).
• Analysis included acute rejection rates, second rejection episodes, antibody treatment, and intrapatient variability of cyclosporine trough concentrations (%CV).

Main Results:

• Gengraf recipients had significantly higher rates of acute rejection (39% vs. 25%, P=0.04) and second rejection episodes (13% vs. 4%, P=0.03) compared to Neoral recipients.
• More Gengraf patients required antibody preparation for acute rejection treatment (19% vs. 8%, P=0.02).
• Gengraf was associated with higher intrapatient variability in cyclosporine trough concentrations (%CV, P<0.05).

Conclusions:

• The generic cyclosporine formulation, Gengraf, was associated with a higher incidence of acute rejection in de novo kidney transplant recipients compared to Neoral.
• Higher intrapatient variability in cyclosporine trough concentrations may contribute to the increased rejection rates observed with Gengraf.
• Further prospective studies are warranted to confirm these findings and guide formulation selection in kidney transplantation.