Adalimumab

Inhibition of inflammatory cytokines (Fig. 2) Humanized monoclonal anti-TNF antibodies (Infliximab (Remicade ), Adalimumab (Humira )) bind with high selectivity to human TNF-a and neutralize its activity. Thereby, infliximab decreases the effects of enhanced TNF levels during inflammatory disease such as production of proteases, chemokines, adhesion molecules, cyclooxygenase products (prostaglandins), and proinflammatory molecules such as interleukin-1 and -6. The antibodies may also recognize membrane-bound TNF-a on lymphocytes and other immune cells. These cells may subsequently become apoptotic or are eliminated via Fc-receptor-mediated phagocytosis. 

Recombinant soluble TNF-RI-IgGl fusion protein Etanercept, Enbrel is a chimeric molecule consisting of the extracellular domain of the TNF receptor I (TNF-RI) and the Fc portion of human IgGl. Two Fc domains are bound to each other via disulfide bonds, thereby yielding dimers with two binding sites for the TNF trimer. Etanercept binds with high affinity to extracellular TNF and reduces TNF activity. Etanercept is not effective in Crohn s disease, possibly because it does not lead to destiuction of membrane TNF-a expressing cells. Indications and side effects are similar to those of Infliximab and Adalimumab. 

Adalimumab Anti-TNFa Rheumatoid arthritis, anklyosing spondylitis... 

Adalimumab Complete human antibody against TNF-a with similar properties as infliximab. 

Commercially available dtugs used for therapeutic therapy comprise up to date mainly injectable monoclonal antibodies like Infliximab (Remicade ) and Adalimumab (Humira ) or TNF-receptor derivatives like Etanercept (Enbrel ) (Fig. 3). One possible way of action of these reagents is the neutralization of TNF, thereby blocking its inflammatory effects and dampening (auto)immune responses [3, 4]. 

Adalimumab (Humira ) is a folly human anti-TNF monoclonal antibody that is mainly used in combination with methotrexate to treat rheumatoid arthritis in adults [3]. Meanwhile, it is also used against arthritis of psoriasis and ankylosing spondylitis. Its therapeutic value in Crohn s disease is under clinical trial. 

Adalimumab (Humira) 40 mg every other week SC injection 1-4 weeks ISR Monitor for infection Screen for tuberculosis... 

Adalimumab is a recombinant human IgGl monoclonal antibody specific for human TNF.27 Adalimumab binds to soluble and bound TNF-a. Patients may experience symptomatic relief in as early as 1 week. Adalimumab can be administered in combination with methotrexate or other DMARDs.2... 

Adalimumab is a TNF-a inhibitor initially approved for the treatment of rheumatoid arthritis in 2003. It is approved for treatment of psoriatic arthritis and off-label uses and clinical... 

Humira (EU USA also sold as Trudexa in EU) (adalimumab r (anti-TNF) human monoclonal antibody created using phage display technology Cambridge Antibody Technologies Abbott (USA) Abbott (EU) Rheumatoid arthritis... 

Adalimumab 40 mg SC every 2 weeks Tuberculin skin test None... 

Adalimumab (Humira) is a human IgGj antibody to TNF that is less antigenic than infliximab. It has response rates similar to other TNF... 

Adalimumab (Humira) is a human immunoglobulin Gj monoclonal TNF-a antibody. The binding of adalimumab results in inactivation of the proinflammatory cytokine TNF-a. It is indicated for psoriatic arthritis and treatment of adults with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. The recommended dose for psoriatic arthritis is 40 mg subcutaneously every other week. The recommended dose for adults with plaque psoriasis is an initial dose of 80 mg, followed by 40 mg every other week starting 1 week after the initial dose. The most common adverse reactions are infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash. 

Infliximab is an anti-TNF antibody that is useful in moderate to severe active disease and steroid-dependent or fistulizing disease but the cost far exceeds that of other regimens. Adalimumab is another anti-TNF antibody... 

Infliximab is used for moderate to severe active Crohn s disease in patients failing immunosuppressive therapy, in those who are corticosteroid dependent, and for treatment of fistulizing disease. A single, 5 mg/kg infusion is effective when given every day for 8 weeks. Additional doses at 2 and 6 weeks following the initial dose results in higher response rates. Adalimumab is effective in 54% of patients with moderate to severe Crohn s disease who have lost response to infliximab. The typical dosage is 160 mg subcutaneously initially, followed by 80 mg subcutaneously at week 2, with subsequent doses of 40 mg subcutaneously every other week thereafter. 

Although the published data are not consistent, there is evidence to suggest that azathioprine, mercaptopurine, methotrexate, infliximab, and adalimumab are effective in maintaining remission in Crohn s disease. 

Infliximab has been associated with infusion reactions, serum sickness, sepsis, and reactivation of latent tuberculosis. Adalimumab carries risks similar to infliximab. 

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. 

Humira Adalimumab Abbott Laboratories, North Chicago, IL Anti-TNF Rheumatoid arthritis 2002... 

Three TNF antagonists are currently approved for the treatment of RA etaner-cept (ETN), infliximab (INF), and adalimumab. ETN a fusion protein of two identical chains of the recombinant human TNF receptor, p75, fused with the Fc portion of human immunoglobulin (Ig) G1 binds to soluble TNF-a in vivo. INF and adalimumab are both monoclonal antibodies to TNF-a INF is chimeric, and adalimumab is fully humanized. Both bind to soluble TNF-a, preventing TNF-a from binding to its receptors on cell surfaces. INF can also bind transmembrane TNF-a, fix complement, and cause cell lysis. 

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... 

In addition to the small molecular weight drugs, various antibodies (adalimumab, ritux-imab, omalizumab), a recombinant form of human IL-l-receptor antagonist (anakinra) and a recombinant fusion protein comprising the... 

Adalimumab is a recombinant, fully human antitumor necrosis factor monoclonal antibody approved in the US and Europe for the treatment of adult patients with moderate to severe, active rheumatoid arthritis. It has to be injected subcutaneously. The most common side effects of adalimumab are injection site reactions. Adalimumab increases the risk of rare serious infections. Rare side effects include worsening or initiation of congestive heart failure, a lupus-like syndrome, a promotion of lymphoma, medically significant cytopenias, and worsening or initiation of a multiple sclerosis like neurological disease. 

Wailoo A, Bansback N, Chilcott J. Infliximab, etaner-cept and adalimumab for the treatment of ankylosing spondylitis cost-effectiveness evidence and NICE... 

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