Efalizumab

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. 

The pharmacokinetics of efalizumab are highly influenced by the target expression, indicating the presence of a receptor-mediated clearance pathway [81-83]. Using purified mouse and human T cells, internalization of anti-CDlla antibodies was observed following interaction with CDlla. Internalized antibodies moved in endosomes to lysosomes and were catabolized within the cells [84, 85]. 

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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. 

Raptiva (efalizumab humanized antibody Genentech (USA) Treatment of adult patients with... 

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. 

Dibucaine (Nupercainal) Doxepin, Topical (Zonalon, Prudoxin) Econazole (Spectazole) Efalizumab (Raptiva) Erythromycin, Topical (A/T/S, Eryderm, Erycette, T-Stat) Erythromycin Benzoyl Peroxide (Benzamycin) Finasteride (Propecia) Fluorouracil, Topical [5-FU] (Efudex) Gentamicin, Topical (Garamycin, G-Mycitin)... 

Efalizumab treatment increases the risk of developing an infection... 

Efalizumab is a recombinant humanized anti-CDlla monoclonal antibody approved for the treatment of adult patients with severe... 

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. 

Dibucaine (Nupercainal) Doxepin, Topical (Zonalon, Prudoxin) Econazole (Spectazole) Efalizumab (Raptiva) ... 

Efalizumab is a humanized IgGlK antibody produced by recombinant DNA technology. It exhibits immunosuppressive function. It binds to CDlla, which is the a-subunit of leukocyte function antigen (LFA)-l. Efalizumab decreases the cell... 

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. 

Dedrick RL, Walicke P, Garovoy M. 2002. Anti-adhesion antibodies efalizumab, a humanized anti-CDl la monoclonal antibody. Transplant Immunol. 9 181-186. 

Graves JE, Nunley K, Heffeman MP. 2007. Off-label uses of biologies in dermatology Rituximab, omalizumab, infliximab, etanercept, adalimumab, efalizumab and alefacept. J Am Acad Dermatol. 56 e55-e79. 

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. 

Due to their high molecular mass (and other reasons), the vast majority of mAbs that have been approved or are currently in clinical development are administered by intravenous (IV) infusion. This route allows the total dose to be available in the circulation, as F (the systemically available fraction of the dose) is, by definition, 1. In consequence, maximum concentrations in serum are rapidly observed, and are higher compared to those achieved by other routes. Therefore, adverse reactions after IV administration occur more often but are generally reversible. In addition, IV infusions represent the most inconvenient (they often require hospitalization) as well as time- and cost-consuming means of administration. Consequently, ex-travascular routes have been chosen as alternatives, including subcutaneous administration (SC e. g., adalimumab, efalizumab) and intramuscular administration (IM e.g., palivizumab) (Table 3.4). 

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