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  • Immunosuppressants and immunomodulators represent an indispensable group of antiinflammatory medications that are capable of treating a wide array of inflammatory skin conditions.

  • The immunosuppressive and immunomodulatory drugs covered in this chapter include mycophenolate mofetil, the calcineurin inhibitors (cyclosporine, tacrolimus, and pimecrolimus), and the mammalian target of rapamycin (mTOR) inhibitor everolimus.

  • The primary goal of therapy with immunosuppressants and immunomodulators is to effectively treat an inflammatory condition while maintaining patient safety.

  • By working in an additive or synergistic fashion, combination regimens have the potential for greater efficacy and may allow for decreased doses of individual drugs, which may enhance overall safety and reduce medication-related side effects.

  • A comprehensive understanding of the pathophysiology of the disease being treated as well as the pharmacokinetic and pharmacodynamic properties of each immunosuppressant and immunomodulator is fundamental to favorable patient outcomes.


There has been significant progress in the field of antiinflammatory therapy. A critical advance has been the successful effort to reduce the use of systemic corticosteroids by the early or concomitant introduction of immunosuppressive or immunomodulatory therapy (or both). Before a detailed discussion of these agents is provided, an important distinction between immunosuppressants and immunomodulators must be made. Immunosuppressants are characterized by a low therapeutic index (narrow window between the therapeutic and toxic range) and significant intra- and interindividual pharmacokinetic variability. These shortcomings are circumvented by precise drug dosing (based on ideal or lean body weight) as well as by screening for end-organ toxicity and, in some cases, close monitoring of plasma drug levels (parent or metabolite peak and trough levels). Immunomodulators, by contrast, have a wider therapeutic index, a greater safety margin, more predictable pharmacokinetic properties, and less interindividual variability. In addition, although immunosuppressants appear to globally impair the host immune response typically in a dose-dependent fashion, immunomodulators may act more selectively by targeting only specific portions of the immune system and therefore pose a lower risk of complications related to immune dysfunction. Whether immunosuppressants or immunomodulators are selected, the primary goals of immunotherapy are safety and efficacy. These goals are best accomplished by using the lowest effective drug doses to achieve disease remission and, in certain scenarios, by using combination therapy (Fig. 192-1).1,2 Among dermatologists, immunosuppressants and immunomodulators are frequently used as corticosteroid-sparing agents.3 This chapter reviews the key pharmacologic properties and prescribing principles of some of the major immunosuppressants and immunomodulators used in dermatology, including mycophenolate mofetil (MMF), the calcineurin inhibitors (CNIs; cyclosporine, tacrolimus, and pimecrolimus), and the mammalian target of rapamycin (mTOR) inhibitor everolimus. Other immunosuppressants, antimetabolites, and cytotoxic agents are discussed in Chap. 190.

Figure 192-1

A modified, median-effect formula is widely used in organ transplantation, which helps in finding the therapeutic windows of immunosuppressive drugs as well as the synergistic, additive, or antagonistic effect of a postulated drug combination. CI, combination index. (Data from Chou TC, Talalay P. Quantitative analysis of ...

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