Immunosuppressive agents in adult kidney transplantation in the National Health Service: a model-based economic evaluation.

BACKGROUND: Immunosuppression is required in kidney transplantation to prevent rejection and prolong graft survival. We conducted an economic evaluation to support England's National Institute for Health and Care Excellence in developing updated guidance on the use of immunosuppression, incorporating new immunosuppressive agents, and addressing changes in pricing and the evidence base. METHODS: A discrete-time state transition model was developed to simulate adult kidney transplant patients over their lifetime. A total of 16 different regimens were modelled to assess the cost-effectiveness of basiliximab and rabbit anti-thymocyte globulin (rabbit ATG) as induction agents (with no antibody induction as a comparator) and immediate-release tacrolimus, prolonged-release tacrolimus, mycophenolate mofetil, mycophenolate sodium, sirolimus, everolimus and belatacept as maintenance agents (with ciclosporin and azathioprine as comparators). Graft survival was extrapolated from acute rejection rates, graft function and post-transplant diabetes rates, all estimated at 12 months post-transplantation. National Health Service (NHS) and personal social services costs were included. Cost-effectiveness thresholds of £20 000 and £30 000 per quality-adjusted life year were used. RESULTS: Basiliximab was predicted to be more effective and less costly than rabbit ATG and induction without antibodies. Immediate-release tacrolimus and mycophenolate mofetil were cost-effective as maintenance therapies. Other therapies were either more expensive and less effective or would only be cost-effective if a threshold in excess of £100 000 per quality-adjusted life year were used. CONCLUSIONS: A regimen comprising induction with basiliximab, followed by maintenance therapy with immediate-release tacrolimus and mycophenolate mofetil, is likely to be effective for uncomplicated adult kidney transplant patients and a cost-effective use of NHS resources.

A Phase 1, randomized, open-label crossover study to evaluate the safety and pharmacokinetics of 400 mg albaconazole administered to healthy participants as a tablet formulation versus a capsule formulation.

BACKGROUND: Albaconazole is a novel triazole being developed for the oral treatment of fungal diseases. Once-weekly oral dosing with 400 mg albaconazole for 24 or 36 weeks resulted in high rates of clinical and mycological resolution for distal subungual onychomycosis, as well as a favorable safety and tolerability profile. PURPOSE: To compare four 100-mg albaconazole capsules to one 400-mg albaconazole tablet for bioavailability, bioequivalence, tolerability, and safety. PATIENTS AND METHODS: Forty participants were enrolled in this Phase I, open-label, two-sequence crossover study. Twenty participants were exposed to a single 400-mg tablet dose of albaconazole before being crossed over to a single dose of four 100-mg albaconazole capsules. The second group of 20 participants received the study products in reverse order. Blood samples were taken over 15 days post-dose to assess the plasma concentrations and pharmacokinetic parameters of albaconazole and its primary metabolite, 6-hydroxyalbaconazole. Safety was assessed throughout the study. RESULTS: The area under the curve (AUC) and maximum measured plasma concentration (C(max)) of the albaconazole tablet were approximately 10% and 22% lower, respectively, than for the albaconazole capsules. Statistical significance was reached for the C(max) but not for the AUC measurements (AUC(0-t) and AUC(0-inf)). Because the 90% confidence intervals based on the differences between the tablet and capsule were outside the 80%-125% range for both the C(max) and AUC, we concluded that the formulations were not bioequivalent with respect to the rate or extent of absorption. Both formulations were safe and well-tolerated in this study. All adverse events (AEs) were generally mild and were mainly gastrointestinal- or nervous system-related (eg, dizziness, headache). No electrocardiogram findings were reported as an AE, and no serious AEs or deaths were reported. CONCLUSION: The AUC and C(max) of albaconazole after a single 400-mg oral dose administered as a tablet formulation were lower than those of a capsule formulation. Albaconazole tablets and capsules cannot, therefore, be considered bioequivalent.