Mycophenolate mofetil efficacy

FK-506 (37) interferes with IL-2 synthesis and release and has a cyclosporin-like profile, but is considerably more potent in vitro. IC q values are approximately 100-fold lower. This neutral macroHde suppresses the mixed lymphocyte reaction T-ceU proliferation generation of cytotoxic T-ceUs production of T-ceU derived soluble mediators, such as IL-2, IL-3, and y-IFN and IL-2 receptor expression (83). StmcturaHy, FK-506 is similar to sirolimus. Mycophenolate mofetil (33), brequinar (34), and deoxyspergualin are in various phases of clinical evaluation. Identification of therapeutic efficacy and safety are important factors in the deterrnination of their utiUty as immunosuppressive agents. 

MPA derivatives have replaced azathioprine as the antiproliferative agent of choice in most organ transplant centers. The MPA derivatives generally are considered to provide a more specific immunosuppressive effect compared with azathioprine. Mycophenolate mofetil and enteric-coated mycophe-nolic acid have similar safety and efficacy data in renal transplant recipients. 

A phase II clinical study of FTY720 in de novo renal transplant patients showed superior efficacy of FTY720 compared to mycophenolate mofetil, if combined with cyclosporine A and steroids [57], In a 1 year, multicentre,... 

Ringe, B., Braun, F., Schiitz, E., Fnzesi, L., Lorf, T., Canelo, R., Oelle-rich, M., Ramadori, G. A novel management strategy of steroid-free immunosuppression after hver transplantation Efficacy and safety of tacrohmus and mycophenolate mofetil. Transplantation 2001 71 508 - 515... 

Fulton B, Markham A (1996) Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation. Drugs 51 278-298. 

Daoird AJ, Schroeder TJ, Shah M, Hariharan S, Peddi VR, Weiskittel P, First MR. A comparison of the safety and efficacy of mycophenolate mofetil, predttisone and cyclosporine and mycophenolate mofetil, and prednisone and tacrohmirs. Trarrsplant Proc 1998 30(8) 4f)79-81. 

Mycophenolate mofetil has been used for patients resistant to or intolerant of cyclophosphamide with good efficacy and limited side effects. A recent controlled study indicates that it may be a better maintenance therapy option than cyclophosphamide. ... 

Mycophenolate mofetil, a semisynthetic morpholinoester of my-cophenolic acid, initially was used to prevent acute rejection after renal and cardiac transplantation, but it is now used as part of combination therapy in moderate to severe psoriasis and other autoimmune dermatoses. It reversibly blocks de novo synthesis of guanine nucleotides required for DNA and RNA synthesis. The drug has been shown to have a speciflc lymphocyte antiproliferative effect. Oral mycophenolate mofetil, as well as topical mycophenolic acid, may undergo further clinical studies to establish efficacy in the treatment of patients with severe psoriasis. " ... 

Zanker B, Schneeberger H, Rothenpieler U, Hillebrand G, Miner WD, Theodorakis I, Stangl M, Land W. Mycophenolate mofetil-based, cyclosporine-free induction and maintenance immunosuppression first-3-months analysis of efficacy and safety in two cohorts of renal allograft recipients. Transplantation 1998 66 44-49. 

Meiser, B. M., Pfeiffer, M., Schmidt, D., Ueherfuhr, P., Reichenspumer, H., Paulus, D., Scheidt, W. V., Kreuzer, E., Seidel, D., and Reichart, B. (1999). The efficacy of the combination of tacrolimus and mycophenolate mofetil for prevention of acute myocardial rejection is dependent on routine monitoring of mycophenolic acid trough acid levels. Transpl. Proc. 31, 84-87. 

The addition of mycophenolate mofetil to ciclosporin has been found to reduce the incidence of rejection episodes in kidney transplant patients and it is licensed for combined use. From the studies above, ciclosporin appears to reduce the levels of the active metabolite, mycophenolic acid, and increase the levels of the glucuronide metabolite (which is associated with mycophenolate adverse effects). The UK manufacturers point out that as efficacy studies were conducted in patients using ciclosporin, mycophenolate and corticosteroids, the finding that ciclosporin reduces the mycophenolic acid AUC by 19% to 38% does not affect the recommended dose requirements. They also state that ciclosporin pharmacokinetics are not affected by mycophenolate. However, this is in contrast to the studies... 

Kamanamool N, McEvoy M, Attia J, Ingsathit A, Ngamjanyaporn P, Thakkinstian A. Efficacy and adverse events of mycophenolate mofetil versus cyclophosphamide for induction therapy of lupus nephritis systematic review and meta-analysis. Medicine (Baltimore) 2010 89(4) 227-35. 

---