Psoriasis alefacept

For the topical treatment of some chronic inflammatory skin diseases (like atopic dermatitis) immunosuppressive macrolides (like TRL and pimecrolimus) that permeate the inflamed epidermis are of benefit for patients. Severe side effects comparable to those after systemic application of TRL in transplanted patients (see above) have not been observed so far. For the treatment of psoriasis vulgaris these drugs are less effective. The CD2 antagonist alefacept may be a suitable alternative to allergic reactions. 

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. 

Alefacept (Amevive) is a dimeric fusion protein that binds to CD2 on T cells to inhibit cutaneous T-cell activation and proliferation. It also produces a dose-dependent decrease in circulating total lymphocytes. Alefacept is approved for treatment of moderate to severe plaque psoriasis and is also effective for treatment of psoriatic arthritis. Significant response is usually achieved after about 3 months of therapy. The recommended dose is 15 mg intramuscularly once weekly for 12 weeks. Adverse effects are mild and include pharyngitis, flu-like symptoms, chills, dizziness, nausea, headache, injection site pain and inflammation, and nonspecific infection. 

Gottlieb, A. et al., Impact of a 12-week course of alefacept therapy on primary and secondary immune responses in psoriasis patients, J. Eur. Acad. Dermatol. Venereol., 15 (Suppl. 2), 242 (Abst. P24-21), 2001. 

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. 

Alefacept (Amevive) is an immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 linked to the Fc portion of human IgGl. Alefacept interferes with lymphocyte activation, which plays a role in the pathophysiology of psoriasis, resulting in a reduction in subsets of CD2 T lymphocytes and circulating total CD4 and CD8 T lymphocyte counts. Alefacept is indicated for the treatment of... 

Alefacept Amevive Chronic plaque psoriasis 2003 (not by EMEA)... 

Fusion proteins Amevive/Alefacept Fusion protein (lgG1/LFA3) Psoriasis... 

Lebwohl, M., E. Christophers, R. Langley, J.P. Ortonne, J. Roberts, and C.E. Griffiths, An international, randomized, double-blind, placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis. Arch. Dermatol., 2003, 139 719-27. 

Alefacept) (US) Approval 2003 fusion protein binds to CD2 on T lymphocytes psoriasis... 

Alefacept Amevive (Biogenidec) Psoriasis, plaque type... 

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

Alefacept is approved for treatment of moderate to severe plaque psoriasis in patients and is also effective for the treatment of psoriatic arthritis. " Significant clinical response is achieved after about 3 months of therapy, and improvements are relatively long lasting. 

Krueger GG, Elhs CN. Alefacept therapy produces remission for patients with chronic plaque psoriasis. Br J Dermatol 2003 148 784-788. 

Ellis CN, Krueger GG, Alefacept Chnical Study Group. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med 2001 345 248-255. 

Feldman, S.R., Menter, A., Koo, J.Y., Improved health-related quality of life following a randomized controlled trial of alefacept treatment in patients with chronic plaque psoriasis. Br. J. Dermatol. 2004, 150, 317-326. 

Alefacept (Amevive, Biogen Idee) and Efalizumab (Reptiva, Xoma, Genentech, Serono), the two monoclonal antibodies, which block the activation of T cells, were hailed as major advances in the treatment of psoriasis. The sales of Reptiva were 112 million and 160 million and of Amevive were 48 and 15 million in 2005 and 2006 below initial sales forecasts mainly due to competition from TNF inhibitors [45]. The technical success of R D of non TNF biologicals for treatment of psoriasis has not translated into commercial success due to the large clinical data base and dominance of TNF antagonist products. 

Therapeutic proteins are normally made in the human body under certain conditions, and synthetic versions of these proteins that are made in labs can be used as medicine. For example, human cells make a protein called interferon in response to viral infections, but synthetic interferon can also be used to treat multiple sclerosis. Two synthetic forms of interferon-1 (3, Rebif, which is made in CHO cells by EMD Serono, and Avonex, also made in CHO cells by Biogen Idee, serve as treatments for multiple sclerosis. Alefacept (brand name Amevive), which is made by AsteUas Pharma, is a fusion protein that blocks the growth of specific T cells (immune cells). No such protein exists in the human body, but alefa-cept is used to treat psoriasis and various cancers. 

---