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Home Books Fitzpatrick's Dermatology in General Medicine, 8e

Chapter 234. Immunobiologicals, Cytokines, and Growth Factors in Dermatology

Stephen K. Richardson; Joel M. Gelfand

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Immunobiologicals, Cytokines, and Growth Factors at a Glance
  • Immunobiologicals are drugs, defined as compounds engineered from living organisms that induce or alter immune responses by interacting with specific biologic targets.
  • Used to treat conditions with immune abnormalities.
  • Those used to treat cutaneous disease include recombinant cytokines and growth factors, monoclonal antibodies, and fusion proteins.
  • Targeting the immune system with biologics may result in an increased risk of infections and malignancies.

Immunobiologicals are compounds synthesized in living organisms that exhibit immune modulatory properties. They consist of recombinant cytokines, growth factors, antibody-based agents, and fusion proteins. Those with dermatologic indications are discussed in this chapter and are listed in Table 234-1. Fig. 234-1 illustrates the molecular targets of these compounds. Fig. 234-2 depicts the cellular events that mediate cutaneous inflammation and identifies the molecular interactions affected by specific immunobiological agents.

Table 234-1 Immunobiologicals, Cytokines, and Growth Factors
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Table 234-1 Immunobiologicals, Cytokines, and Growth Factors

Action

Dosing for Dermatologic Indications

Recombinant interferons

Interferon-α and Interferon-γ

  • Enhances cell-mediated cytotoxicity against viral disease and malignancy via promotion of MHC expression and suppression of Th2 cytokine production
  • Variable

Recombinant Interleukins and growth factors

Interleukin 2

  • Maintains helper T-cell populations
  • Enhances natural killer cell cytotoxicity and lymphokine activated cell activity
  • Variable

Interleukin 1 receptor antagonist

  • Blocks the interaction between IL1 and its receptor
  • Suppresses IL1 mediated inflammatory responses (e.g., leukocyte recruitment, osteoclast activation)
  • Variable

Granulocyte-macrophage colony-stimulating factor

  • Promotes the proliferation and differentiation of myeloid precursors
  • Variable

Platelet-derived growth factor

  • Promotes wound healing via angiogenic activity and proliferative effects on fibroblasts and smooth muscle cells
  • Daily application of gel to affected site

Antibody-based therapeutics

Anti-TNF-α

  • Infliximab: chimeric monoclonal antibody; neutralizes both membrane-bound and soluble TNF-α
  • Adalimumab: human monoclonal antibody; neutralizes both membrane-bound and soluble TNF-α
  • 5-mg/kg IV at week 0, 2, and 6, then q8wk 80-mg SC followed by 40-mg SC 1 week later, then 40-mg SC qow
  • 80 mg SC followed by 40 mg SC 1 week later, then 40 mg SC qow

Anti-IL12/IL23

  • Ustekinumab: human monoclonal antibody; inhibits IL-12 and IL-23 mediated inflammatory processes
  • Patients <100 kg: 45-mg SC followed by same dose at week 4, and q12wk thereafter
  • (Patients >100 kg: receive 90 mg)

Anti-LFA-1

  • Efalizumab: humanized monoclonal antibody; interferes with lymphocyte activation, cytotoxicity, and trafficking to the skin; withdrawn from US market in 2009 because of PML
  • 0.7-mg/kg SC followed by 1 mg/kg qwk

Anti-CD20

  • Rituximab: chimeric monoclonal antibody; promotes a reduction in CD20+ cells (B-cells)
  • Variable

Fusion proteins

Alefacept

  • Human IgG1 Fc region fused to LFA-3 extracellular domain; interferes with T-cell activation by blocking the interaction between LFA-3 and CD2
  • 15 mg IM qwk for 12 weeks

Etanercept

  • Human IgG1 Fc region fused to TNF type II receptor domain; neutralizes soluble TNF-α
  • 50-mg SC biw for 12 weeks, then 50-mg SC qwk

Denileukin Diftitox

  • Diphtheria-toxin component fused to IL2; promotes apoptosis of T-cells expressing the high affinity IL2 ...

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