Immunosuppressive therapy mycophenolate mofetil

APCs, antigen-producing cells MMF, mycophenolate mofetil OKT-3, muronomab-CD3. (Adapted from Mueller XM. Drug immunosuppressive therapy for adult heart transplantation I. Immune response to allograft and mechanism of action of immunosuppressants. Ann Thorac Surg 2004 77 354-362, with permission.)... 

FIGURE 52-2. Center-specific protocols may use RATG, an IL-2RA, or no induction therapy. In any situation, patients receive IV methylprednisolone prior to, during, or immediately following the transplant operation. The patient then will begin the maintenance immunosuppressive regimen. The center-specific protocol will specify which calcineurin inhibitor (cyclosporine or tacrolimus) is used in combination with mycophenolate mofetil or sirolimus with or without steroids. Patients then are monitored for signs and symptoms of rejection. 

Sirolimus is currently the only FDA-approved ToR inhibitor. One of its derivatives, everolimus, is in phase III clinical trials and has been approved for use in some European countries.30 Sirolimus is a macrolide antibiotic that has no effect on cal-cineurin phosphatase.11,31,32 Sirolimus inhibits T cell activation and proliferation by binding to and inhibiting the activation of the mammalian ToR, which suppresses cellular response to IL-2 and other cytokines (i.e., IL-4 and IL-15J.11,31 Studies have shown that sirolimus may be used safely and effectively with either cyclosporine or tacrolimus as a replacement for either azathioprine or mycophenolate mofetil.33 However, when using both sirolimus and cyclosporine as part of a patient s immunosuppressant therapy, because of a drug interaction between the two resulting in a marked increase in sirolimus concentrations, it is recommended to separate the sirolimus and cyclosporine doses by at least 4 hours. Sirolimus also can be used as an alternative agent for patients who do not tolerate calcineurin inhibitors due to nephrotoxicity or other adverse events.34... 

Mycophenolic acid (MPA) was isolated from cultures of Penicillium spp. in 1896 and was purified in 1913. Initially the compound was studied for its antifungal and antibacterial effects and later for its antitumor effects. Many years later, its immunosuppressive activities were recognized and after further developmental work, an ester prodrug mycophenolate mofetil was developed, which was approved by the United States Food and Drug Administration for the prevention of acute renal allograft rejection in 1995 and for heart transplant recipients in 1998. Mycophenolate mofetil is a cytotoxic agent now used for immunosuppressive therapy and is the mofetil ester of MPA, which is the active immunosuppressive agent. 

To evalnate whether mycophenolate mofetil is effective in treating moderate to severe atopic dermatitis, an open pilot stndy was condncted in 10 patients (34). There were no serions adverse effects, bnt one patient had to discon-tinne treatment becanse he developed Herpes simplex retinitis, which resolved after treatment with aciclovir. Althongh there is no direct evidence that mycophenolate mofetil is a major canse of Herpes retinitis, in this patient it seems likely that it was dne to immunosuppression. In contrast, in vivo and in vitro mycophenolate mofetil strongly potentiates the antiherpetic effects of aciclovir, ganciclovir, and penciclovir (35). It is probably therefore enough to give antiviral therapy only when clinical signs of Herpes infection occur. 

Mycophenolate mofetil (MMF), an immunosuppressant used in organ transplant, has cleared refractory symptoms of AD in short-term, open-label studies. Since dose finding and weU-controlled studies are not available for MMF use in AD, the agent should be used with caution and discontinued if the patient does not respond within 4 to 8 weeks of therapy. ... 

Various immunosuppressive drugs have been employed in SSc-ILD including cyclophosphamide, azathioprine, and mycophenolate mofetil (MMF). The most frequent treatment regimen involves low-dose prednisolone (<10 mg/day or 20 mg on alternate days). Higher-dose corticosteroid therapy has been implicated in the precipitation of renal crises. 

Modification of the standard triple drug therapy (CsA, AZA, corticosteroids) is not unusual and the clinical introduction of other potent immunosuppressive drugs such as mycophenolate mofetil... 

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