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Anti-TNF agents

Immunological mechanisms are important in the development and perpetuation of psoriatic arthritis. Thus, it is reasonable to consider that anti-TNF agents would control the signs and symptoms of the disease and prevent the progression of joint damage.

Two groups of anti-TNF agents have been developed: TNF receptor fusion protein and anti-TNF antibodies.

TNF receptor fusion protein

Etanercept (Enbrel®) is a fusion protein of the p75 TNF receptor. It has been used successfully in the treatment of autoimmune disorders, such as rheumatoid arthritis, psoriatic arthritis and psoriasis. Etanercept binds to the TNF circulating in the blood, but it does not necessarily block all TNF activity.

Method of administration
Etanercept is given by an injection of 25 mg under the skin (subcutaneously) twice a week. It is usually self-injected. For psoriasis, a dose of 50 mg twice a week for the first 3 months is used and then the dose is reduced to 25 mg. Some patients may notice a response within 4 weeks; most will notice a benefit by 12 weeks. There may be continued improvement over 9 months before the response plateaus.

There are other TNF receptor fusion proteins in various stages of development and undergoing clinical trials, but they have not yet received regulatory approval.

Anti-TNF antibodies

Inflximab (Remicade®) is a chimeric anti-TNF antibody, which is mostly of human origin, but with a small fragment that is derived from mice. It blocks TNF activity occurring both on the cell surface and in the blood.

Infliximab is approved to treat autoimmune disorders, such as ankylosing spondylitis, Crohn's disease, psoriasis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis. Studies with infliximab, both in psoriasis and psoriatic arthritis, have been very successful in improving inflammation. Infliximab may prevent progression of joint damage in psoriatic arthritis.

Method of administration
Infliximab is given by infusion of 5 mg/kg per infusion at 0, 2, 6 and 8 weeks, and then every 8 weeks thereafter. The infusion usually takes 2-3 hours. Patients often feel very well after the first infusion. A response is usually noticed by the fourth infusion. Many patients continue to do well with infusions every 8 weeks. Some patients require more frequent infusions.

Adalimumab (Humira®) is a fully human anti-TNF antibody. Adalimumab is an injectable protein that blocks the inflammatory effects of TNF-alpha. It is used to treat chronic inflammatory diseases, such as rheumatoid arthritis, psoriatic arthritis, psoriasis, ankylosing spondylitis, and Crohn's disease.

Method of administration
Adalimumab is given by an injection under the skin every 2 weeks.

Golimumab (Simponi™) is a human monoclonal antibody that targets and neutralizes excess TNF-alpha in the body. Over production of TNF triggers chronic inflammation, leading to joint and tissue damage. Golimumab is approved for the treatment of adults with moderate-to-severe active rheumatoid arthritis, active psoriatic arthritis and active ankylosing spondylitis.

Method of administration
Golimumab is administered as a 50 mg subcutaneous injection once a month.
  • For psoriatic arthritis, golimumab may be used with or without methotrexate, an immunosuppressant drug.
  • For rheumatoid arthritis, golimumab is intended to be used with methotrexate.

Side effects of anti-TNF agents

In clinical trials, anti-TNF agents appeared to be safe and well tolerated. Injection site reactions are common. These drugs have now been used extensively, but there is concern over the risk of infections and reactivation of latent or new onset tuberculosis (TB). As with all TNF-blocking agents, these drugs are required to carry a boxed warning that alerts patients and health care professionals to the risk of invasive fungal infections and TB. In addition, there is concern about an increased risk of lymphoma, and development of demyelinating disease, such as multiple sclerosis. It is important to note that each TNF inhibitor has a distinct side effect profile.

Side effects

  • Serious infections
    - Opportunistic infections and reactivation of Tuberculosis
    - These opportunistic infections are commoner with Infliximab
    - Screening for previous TB exposure before treating with TNF antagonists reduces the risk of Tuberculosis reactivation
  • Hematological (blood) events
  • Demyelination
    - These drugs should not be used in those with a history of MS.
    - They might be contraindicated in those patients with first-degree relatives with MS
  • Autoantibodies and lupus like syndrome
  • Congestive heart failure
    - These drugs should not be used if there is significant Cardiac failure. The risks for Etanercept and Adalimumab are less clear
  • Hepatotoxicity
    - Lab tests show elevations in liver enzymes although jaundice, liver failure has not been seen. The risk is higher in those with obesity, excess alcohol consumption and previous use of Methotrexate.These drugs should not be used in hepatitis B patients. Interestingly Etanercept is used as a treatment for hepatitis C
  • Malignancies
    - There does not seem to be an increase risk for non-lymphoma solid cancers. There is a slight increase risk on lymphomas.
    - There may be an increased of lymphoma in Rheumatoid arthritis as well as possibly psoriasis

People who are considering using these medication should have a TB skin test and a chest x-ray before beginning these treatments. People on these drugs should contact their physicians immediately if there is any suspicion of infection.

Although there were no specific laboratory abnormalities detected in patients treated with anti-TNF agents, we routinely check hematology, liver and kidney function tests.

None of the biologic medications have been tested during pregnancy and patients should avoid becoming pregnant while taking them.

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