Psoriasis efalizumab

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. 

Joshi, A., Bauer, R., Kuebler, P, White, M., Leddy, C., Compton, P., Garovoy, M., Kwon, P., Walicke, P., and Dedrick, R. 2006. An overview of the pharmacokinetics and pharmacodynamics of efalizumab a monoclonal antibody approved for use in psoriasis. Journal of Clinical Pharmacology 46(1), 10-20. 

Examples of antibodies in the market include trastuzumab (anti-HER2 monoclonal antibody), rituximab, natalizumab (x4-integiin antibody), abciximab, infiximab (targets TNF-a in Crohn s disease and rheumatoid arthritis), alemtuzumab, adalimumab (TNF-a antibody for the treatment of rheumatoid arthritis) and efalizumab (anti-CDlla monoclonal antibody for the treatment of psoriasis)Rituximab is a mouse/human chimeric anti-CD20 monoclonal antibody used for the treatment of various l)unphoid malignancies. As CE)20 antigen is found on the surface of... 

Lebwohl M, Tyring SK, Hamilton TK, et al. A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J Med 2003 349 2004-13. 

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. 

Efalizumab is administered weekly by subcutaneous injections to treat psoriasis, where a steady state is reached after 4 weeks. Its side effects include serious infections, thrombocytopenia, hemolytic anemia and the probability of malignancies due to its immunosuppressive effects. Other common side effects produced by efalizumab within 2 weeks of administration are nausea, fever, chills and headache. Furthermore, it can produce symptoms associated with hypersensitivity reaction. 

Menter A, Leonardi CL, Sterry W, Bos JD. 2006. Long-term management of plaque psoriasis with continuous efalizumab therapy. J Am Acad Dermatol. 54 S182-S188. 

Raptiva Efalizumab Humanized IgGi CDlla Plaque psoriasis sc 1 mg/kg Weekly... 

The population PK/PD of efalizumab were recently evaluated in patients with moderate to severe plaque psoriasis following SC administration of 1.0 and 2.0 mg/kg for 12 weeks [81-83]. Steady-state serum concentrations were achieved by four to eight weeks following administration of 1 and 2 mg/kg doses, respectively. At both doses, CDlla expression on T lymphocytes was reported to be maximally down-modulated. In addition, at doses of 1 and 2 mg/kg, >95 % of CDlla binding-sites were reported to be saturated at steady-state serum trough concentrations of 9 and 24 pg/mL, respectively. The improvement in PAS I scores was observed quickly, and efalizumab administration was reported to result in 60-70% improvement in PASI scores when compared to baseline after 12 weeks of treatment. The current recommended dose for efalizumab is a single 0.7 mg SC conditioning dose which is followed by weekly SC doses of 1 mg/kg. 

J.G. Krueger, C. Leonardi, B. Miller, and A. Joshi. 2005. Pharmacokinetics and pharmacodynamics of multiple weekly subcutaneous efalizumab doses in patients with plaque psoriasis./. Clin. Pharmacol. 45 286—298. 

Sun,Y.N., J.F. Lu, A. Joshi, P. Compton, P. Kwon, and R.A. Bruno. 2005. Population pharmacokinetics of efalizumab (humanized monoclonal anti-CDll a antibody) following long-term subcutaneous weekly dosing in psoriasis subjects./. Clin. Pharmacol. 45 468—476. 

Menter, A., M. Kosinski, B.W. Bresnahan, K.A. Papp, and J.E. Ware, Jr., Impact of efalizumab on psoriasis-specific patient-reported outcomes. Results from three randomized, placebo-controlled clinical trials of moderate to severe plaque psoriasis. J. Drugs. Dermatol., 2004, 3 27-38. 

Raptiva efalizumab (2003) Anti-CDlla (T cells) (mAb-IgGl) Psoriasis Mouse—murine homologue (F, EFD, PPD)... 

Efalizumab Raptiva Genentech Anti-CDlla IgGl kappa Psoriasis 2003... 

Raptiva Efalizumab Genentech 10/2003 Chronic plaque psoriasis CHO... 

Gordon, K. B., Papp, K. A., Hamilton, T. K., Walicke, P. A., Dummer, W., Li, N., Bresnahan, B. W., and Menter, A. (2003). Efalizumab for patients vrith moderate to severe plaque psoriasis A randomized controlled trial. Jama 290, 3073-3080. Harpaz, Y., and Chothia, C. (1994). Many of the immoglobulin superfamily domains in cell adhesion molecules and surface receptors belong to a new structural set which is close to that containing variable domains. J. Mol. Biol. 238, 528-539. 

Clinical studies with efalizumab have shown efficacy with few adverse effects. In an open-label, multicenter, dose-escalating study of repeated intravenous infusions of efalizumab over 7 weeks in 39 subjects with moderate to severe psoriasis, the individuals who were exposed to the optimum dose (1 mg/kg weekly) showed a mean decrease in PASI of 47%. A subcutaneous formulation is under investigation. 

Gottlieb AB, Krueger JG, Wittkowski K, et al. Psoriasis as a model for T-cell-mediated disease immunobiologic and clinical effects of treatment with multiple doses of efalizumab, an anti-CD 1 la antibody. Arch Dermatol 2002 138 591-600. 

USA efalizumab antibody Raptiva Xanelim Recombinant humanized MAb directed against CD-11 and expressed in CHO cells Psoriasis... 

Efalizumab Raptiva Genentech, Serono humanized mAb CDlla psoriasis 2003 IgGl 6%... 

Efalizumab is a monoclonal antibody that inhibits the activation of T lymphocytes. It is licensed for severe plaque psoriasis resistant to other systemic treatment and phototherapy. Presumably, efalizumab works by inhibiting the inflammatory component of this type of psoriasis. 

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