Arthritis, treatment monoclonal antibody therapy

Keystone, E. C., Kavanaugh, A. E., Sharp, J. T., et al. (2004) Radiographic, cUnical, and functional outcomes of treatment with adaUmumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy a randomized, placebo-controUed, 52-week trial. Arthritis and Rheumatism. 50, 1400-1411. 

The first therapeutic antibody approved (Orthoclone OKT-3 or Muromonab CD3, 1986) was indicated not for cancer treatment, but for controlling acute rejection of transplanted organs (kidney, heart, and liver). Nowadays, other clinical indications such as asthma, rheumatoid arthritis, psoriasis, and Crohn s disease are treated with mAbs (see Chapter 17) (Antibody Engineering and Manufacture, 2005 Monoclonal Antibodies and Therapies, 2004 Hot Drugs, 2004 Walsh, 2004). 

Infliximab (in FLICKS ih mab) is a chimeric IgGic monoclonal antibody composed of human and murine regions. The antibody binds specifically to human TNF-a, thereby neutralizing that cytokine. Infliximab has been approved for Crohn s disease for both fistulizing and non-fistula disease. [Note Increased levels of TNF-a are found in fecal samples of patients with Crohn s disease.] It is not approved for maintenance therapy beyond six weeks. Approval for the treatment of rheumatic arthritis in combination with methotrexate is anticipated in the near future. 

Another TNFa monoclonal antibody known as etanercept (a fusion protein of human IgG and two p75 TNF receptors) [98] that is a competitive inhibitor of TNF s cell-surface receptor has been developed. Clinical studies have shown that etanercept therapy results in significant clinical benefits and is well tolerated and safe for long-term use [99-101]. Etanercept is given subcutaneously (25 mg) twice weekly for the treatment of rheumatoid arthritis [98]. It is also used in the treatment of psoriatic arthritis, and a recent clinical trial has reported that in addition to decreasing joint pain and fatigue, etanercept also decreases symptoms of depression associated with this chronic disease [102]. 

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. 

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