Mycophenolate Mofetil: A Dermatologic Perspective
Mycophenolate Mofetil: A Dermatologic Perspective
Introduced in the 1970s as a treatment for psoriasis, mycophenolic acid has since been reformulated as mycophenolate mofetil (MMF). With an improved side-effect profile and enhanced bioavailability, MMF is a promising drug for immune-mediated skin disease. Currently approved for the prevention of organ rejection, its list of "off-label" dermatologic indications continues to grow. As a noncompetitive inhibitor of inosine monophosphate dehydrogenase (IMPDH), MMF inhibits de novo purine synthesis. Its relative lack of hepatonephrotoxicity and seemingly low risk of carcinogenicity offer important therapeutic advantages. While case reports and case series dominate the dermatologic literature, preliminary results are sufficiently promising to warrant larger, randomized clinical trials with this emerging therapy.
In the past two decades, an increasing number of immunosuppressive agents have been developed to prevent allograft rejection in organ transplantation. A number of these medications have shown therapeutic efficacy in inflammatory skin disease; however, patients and physicians must be mindful of their toxicities. Originally isolated from cultures of Penicillium stoloniferum, mycophenolic acid (MPA) was first recognized as a lipid-soluble, weak organic acid. It was later shown to have antibacterial, antiviral, antifungal, antitumoral and immunosuppressive properties. In 1975, MPA demonstrated therapeutic efficacy in psoriasis. However, it soon fell into disrepute with growing concerns about its long-term risk of carcinogenicity. Moreover, tolerability of MPA was limited by gastrointestinal upset. Subsequent investigations led to the development of mycophenolate mofetil (MMF) (CellCept, Roche Pharmaceuticals), the semi-synthetic 2-morpholinoethyl ester of MPA. This new formulation showed enhanced bioavailability, tolerability and efficacy. By 1995, MMF received US FDA approval for the prevention of acute renal allograft rejection and soon became recognized as an effective treatment option for immune-mediated skin disease.
Introduced in the 1970s as a treatment for psoriasis, mycophenolic acid has since been reformulated as mycophenolate mofetil (MMF). With an improved side-effect profile and enhanced bioavailability, MMF is a promising drug for immune-mediated skin disease. Currently approved for the prevention of organ rejection, its list of "off-label" dermatologic indications continues to grow. As a noncompetitive inhibitor of inosine monophosphate dehydrogenase (IMPDH), MMF inhibits de novo purine synthesis. Its relative lack of hepatonephrotoxicity and seemingly low risk of carcinogenicity offer important therapeutic advantages. While case reports and case series dominate the dermatologic literature, preliminary results are sufficiently promising to warrant larger, randomized clinical trials with this emerging therapy.
In the past two decades, an increasing number of immunosuppressive agents have been developed to prevent allograft rejection in organ transplantation. A number of these medications have shown therapeutic efficacy in inflammatory skin disease; however, patients and physicians must be mindful of their toxicities. Originally isolated from cultures of Penicillium stoloniferum, mycophenolic acid (MPA) was first recognized as a lipid-soluble, weak organic acid. It was later shown to have antibacterial, antiviral, antifungal, antitumoral and immunosuppressive properties. In 1975, MPA demonstrated therapeutic efficacy in psoriasis. However, it soon fell into disrepute with growing concerns about its long-term risk of carcinogenicity. Moreover, tolerability of MPA was limited by gastrointestinal upset. Subsequent investigations led to the development of mycophenolate mofetil (MMF) (CellCept, Roche Pharmaceuticals), the semi-synthetic 2-morpholinoethyl ester of MPA. This new formulation showed enhanced bioavailability, tolerability and efficacy. By 1995, MMF received US FDA approval for the prevention of acute renal allograft rejection and soon became recognized as an effective treatment option for immune-mediated skin disease.
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