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Chapter: Basic & Clinical Pharmacology : Dermatologic Pharmacology

Biologic Agents

Biologic agents useful in treating adult patients with moderate to severe chronic plaque psoriasis include the T-cell modulator ale-facept, the TNF-α inhibitors etanercept, infliximab, and adali-mumab, and the cytokine inhibitor ustekinumab.

BIOLOGIC AGENTS

Biologic agents useful in treating adult patients with moderate to severe chronic plaque psoriasis include the T-cell modulator ale-facept, the TNF-α inhibitors etanercept, infliximab, and adali-mumab, and the cytokine inhibitor ustekinumab.

ALEFACEPT

Alefacept (Amevive) is an immunosuppressive dimeric fusion pro-tein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 linked to the Fc portion of human IgG1. Alefacept interferes with lymphocyte activation, which plays a role in the pathophysiology of psoriasis, and causes a reduction in subsets of CD2 T lymphocytes and circulating total CD4 and CD8 T-lymphocyte counts. The recommended dosage is 7.5 mg given once weekly as an intravenous bolus or 15 mg once weekly as an intramuscular injection for a 12-week course of treat-ment. Patients should have CD4 lymphocyte counts monitored weekly while taking alefacept, and dosing should be withheld if CD4 counts are below 250 cells/μL. The drug should be discontin-ued if the counts remain below 250 cells/μL for 1 month. Alefacept is an immunosuppressive agent and should not be administered to patients with clinically significant infection. Because of the possi-bility of an increased risk of malignancy, it should not be adminis-tered to patients with a history of systemic malignancy.

TNF INHIBITORS: ETANERCEPT, INFLIXIMAB, & ADALIMUMAB

Etanercept (Enbrel) is a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human TNF receptor linked to the Fc portion of human IgG1. Etanercept binds selectively to TNF-α and -β and blocks interaction with cell surface TNF receptors that play a role in the inflammatory process of plaque psoriasis. The recommended dosage of etanercept in psoriasis is a 50 mg subcutaneous injection given twice weekly for 3 months followed by a maintenance dose of 50 mg weekly.

Infliximab (Remicade) is a chimeric IgG1 monoclonal anti-body composed of human constant and murine variable regions. Infliximab binds to the soluble and transmembrane forms of TNF-α and inhibits binding of TNF-α with its receptors. The recommended dose of infliximab is 5 mg/kg given as an intrave-nous infusion followed by similar doses at 2 and 6 weeks after the first infusion and then every 8 weeks thereafter.

Adalimumab (Humira) is a recombinant 1gG1 monoclonal antibody that binds specifically to TNF-α and blocks its interac-tion with cell surface TNF receptors. The recommended dose for adalimumab in psoriasis is an initial dose of 80 mg administered subcutaneously followed by 40 mg given every other week starting 1 week after the initial dose.

Serious life-threatening infections, including sepsis and pneu-monia, have been reported with the use of TNF inhibitors. Patients should be evaluated for tuberculosis risk factors and tested for latent tuberculosis infection prior to starting therapy. Concurrent use with other immunosuppressive therapy should be avoided. In clinical trials of all TNF-blocking agents more cases of lymphoma were observed compared with control patients. Patients with a prior history of prolonged phototherapy treatment should be monitored for nonmelanoma skin cancers.

USTEKINUMAB

Ustekinumab (Stelara) is a human IgG1κ monoclonal antibody that binds with high affinity and specificity to interleukin (IL)-12 and IL-23 cytokines inhibiting TH1 and TH17 cell-mediated responses, which are involved in the pathogenesis of psoriasis. The recom-mended treatment protocol is 45 mg for patients weighing less than 100 kg and 90 mg for patients weighing more than 100 kg given as a subcutaneous injection initially, followed by the same dose 4 weeks later, and then once every 12 weeks. Serious allergic reactions includ-ing angioedema and anaphylaxis have occurred and caution should be exercised in patients receiving allergy immunotherapy. Serious infections, especially from mycobacterial organisms, are possible and patients must be evaluated for tuberculosis prior to initiating therapy. Live vaccines, including Bacillus Calmette-Guérin (BCG), should not be given with ustekinumab. One case of reversible posterior leukoencephalopathy syndrome (RPLS) has been reported.


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