Infliximab psoriasis

Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.17 29 Oral agents include sulfasalazine, acitretin, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the biologic response modifiers alefacept, efalizumab, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis. 

Infliximab (Remicade) is a chimeric monoclonal antibody directed against TNF-a. Recently, its indications have been expanded to include psoriatic arthritis and treatment of adults with chronic severe plaque psoriasis. An advantage over other systemic psoriasis treatments is that infliximab does not adversely affect blood counts, hepatic enzyme levels, or kidney function. The recommended dose is 5 mg/kg as an IV infusion at weeks 0, 2, and 6, then every 8 weeks thereafter. For psoriatic arthritis, it may be used with or without methotrexate. Adverse effects include headaches, fever, chills, fatigue, diarrhea, pharyngitis, upper respiratory and urinary tract infec-... 

Several pro-inflammatory cytokines, such as TNFa, IL-1, IL-6, are important in the initiation and maintenance of various autoimmune diseases, such as RA, CD, and psoriasis. Thus, targeted therapies, which have been developed to inhibit their activity, have resulted in clinical improvement of these patients. Currently, there are three TNFa inhibitors (etanercept, infliximab, and adalimumab) and one IL-1 receptor antagonist (anakinra) that have been approved for the treatment of at least one of these diseases. In addition, a number of other anti-cytokine therapies are in clinical development. The TNFa antagonists will be reviewed here. 

Etanercept is a recombinant human soluble tumor necrosis factor-alpha (TNFo ) receptor fusion protein that binds to TNFo and decreases its role in disorders involving excess inflammation. It is approved for subcutaneous use in the treatment of patients with moderate to severe active rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing arthritis and plaque psoriasis. To the adverse reactions mentioned for infliximab, rare reports of congestive heart failure should be added. 

Infliximab is a monoclonal antibody against TNF-a (see Chapter 26, Section III.d.1). It has been approved for the treatment of psoriasis, Crohn s disease, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis and ulcerative colitis. Similar immunosuppressants are etanercept, and adali-mumab. 

Weinberg JM et al Biologic therapy for psoriasis An update on the tumor necrosis factor inhibitors infliximab, etanercept, and adalimumab, and the T-cell-targeted therapies efalizumab and alefacept. J Drugs Dermatol 2005 4 544. [PMID 16167412]... 

Biologic agents useful in treating adult patients with moderate to severe chronic plaque psoriasis include the T-cell modulators alefacept and efalizumab, and the TNF-a inhibitors etanercept, infliximab, and adalimumab. TNF-a inhibitors are also discussed in Chapter 55. 

The biologic agents currently used in moderate to severe psoriasis treatment are infliximab, etanercept, alefacept, and efaliznmab. 

Infliximab is a chimeric monoclonal antibody (immunoglobuhn Gj IgGi) directed against TNF-a. It binds with high affinity to the soluble and transmembranous forms of TNF-a and inhibits binding of TNF-a with its receptors. TNF-a is beheved to play an important role in the pathogenesis of psoriasis. Increased amounts of TNF-a have been found in psoriatic lesions. The proposed mechanism of action... 

Infliximab is approved for treatment of rheumatoid arthritis and Crohn s disease, but has been studied for use in psoriasis. One double-blind, randomized, placebo-controUed clinical trial studied the effectiveness and safety of infliximab in patients with moderate to severe psoriasis. A good response was seen in 82% and 91% of patients treated with infliximab 5 mg/kg or 10 mg/kg, respectively. Median time to response for all patients receiving infliximab was 4 weeks. The investigators concluded that patients treated with infliximab had a high degree of clinical improvement with rapid response rate, similar to that observed with cyclosporine therapy. ... 

The most common adverse effects of infliximab are headaches, fever, chills, fatigue, diarrhea, pharyngitis, upper respiratory and urinary tract infections, and hypersensitivity reactions (urticaria, dyspnea, and hypotension). Infliximab has been also associated with infections and lymphoproliferative disorders. It is not associated with end-organ toxicity, and blood counts, liver enzyme levels, kidney function, and complement values can be expected to remain normal during treatment. This gives it a major advantage over other systemic psoriasis treatments. 

Gottlieb AB. Infliximab for psoriasis. J Am Acad Dermatol 2003 49 S112-S117. 

Chaudhari U, Romano P, Mulcahy LD, et al. Efficacy and safety of infliximab monotherapy for plaque-type psoriasis a randomised trial. Lancet 2001 357 1842-1847. 

Infliximab (Remicade) is a mouse-human chimeric monoclonal antibody that binds to soluble and membrane-bound TNF-a and inhibits binding with its receptors. Infliximab is a complement-fixing antibody that induces complement-dependent and cell-mediated lysis when bound to cell-surface-bound TNF-a. It also induces proinflammatory cytokines, such as IL-1 and IL-6, and enhances leukocyte migration. Infliximab is FDA approved for the treatment of Crohn s disease and rheumatoid arthritis, but it is also in phase trials for the treatment of psoriasis. 

The pioneering work on monoclonal antibodies against TNF-a originate from Junming Le and Jan VUcek at the New York University School of Medicine. Infliximab (Retnicade ) is a chimeric, monoclonal anti-TNF-a-antibody (human/ mouse), which is approved for the treatment of rheumatoid arthritis, Crohn s disease (a chronic inflammatory disease of the intestine) and psoriasis. [210]... 

Lichenoid reactions are uncommon but may be an emerging cutaneous adverse reaction to TNF alfa antagonists, as in a 37-year-old man who developed hchen pla-nopilaris after taking infliximab for 11 months for long-standing refractory psoriasis. [55 ]. 

Immunologic Anti-DNA antibodies and antinuclear antibodies have been described in up to 14% of patients taking infliximab and etanercept. A 40-year-old woman with psoriasis developed biopsy-proven drug-induced hepatitis and concurrent lupus-like... 

There is also an increased risk of viral infections associated with the use of TNF alfa antagonists. A patient with psoriasis developed a fatal respiratory tract infection with HlNl influenza A 1 week after a first infusion of infliximab [63 ]. 

Poulin Y, Therien G. Drug-induced hepatitis and lupus during infliximab treatment for psoriasis case report and literature review. J Cutan Med Surg 2010 14(2) 100-. ... 

Kling MC, Larian AA, Scordi-Bello I, Emer J, Lebwohl MG. Fatal influenza A(HINI) respiratory tract infection in a patient having psoriasis treated with infliximab. Arch Dermatol 2010 146(6) 651-4. 

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