Arthritis drug new rheumatoid

by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

Click here: Second Opinion Arthritis Treatment Kit

Researchers are working hard to understand what triggers the autoimmune reactions that cause the symptoms of rheumatoid arthritis and what can be done to relieve these symptoms. Despite many impressive developments, there's still no cure.

Information from the Arthritis Foundation, the American College of Rheumatology, and the National Institutes of Health

Biological treatments target the parts of the body's immune system that trigger joint damage and inflammation. TNF-alpha inhibitors are one type of biological treatment approved for rheumatoid arthritis.

For people with inflammatory conditions who have tried other medications with little success, TNF-alpha inhibitors may provide some relief. Also known as biologic response modifiers, these new prescription drugs block the action of tumor necrosis factor-alpha (TNF-alpha), a protein that's present in larger quantities in the body with diseases such as rheumatoid arthritis.

But, like all medications, TNF-alpha inhibitors may cause side effects that a patient should consider when deciding to take these drugs. Balancing the side effects and financial cost with the potential improvements in the quality of life that could come from taking TNF-alpha inhibitors is something a patient needs to discuss with their rheumatologist.

How TNF-alpha inhibitors work

The body naturally produces the protein TNF-alpha to stimulate white blood cells to fight infections and other invaders. This temporarily causes inflammation in the affected area. Normally the body would then get rid of the TNF-alpha. But if a person has rheumatoid arthritis, the body doesn't remove the TNF-alpha. This causes more and more white blood cells to travel to the affected area. As TNF-alpha continues to accumulate, it causes chronic inflammation, which can lead not only to to pain but to tissue damage.

TNF-alpha inhibitors block the action of TNF-alpha in the body. By preventing TNF-alpha from acting, these drugs reduce inflammation and other signs and symptoms a patient may have.

Five TNF-alpha inhibitors are available.

Adalimumab (Humira) is administered by the patient under the skin of the thigh or stomach every other week, or sometimes weekly. Adalimumab can be used alone, or may also be prescribed with other medications along with it, such as methotrexate.

Research conducted since Food and Drug Administration approval of adalimumab (Humira) shows that in rare circumstances the medication has been associated with severe allergic reactions (anaphylaxis) as well as with various infections and blood disorders.

Etanercept (Enbrel), the first TNF-alpha inhibitor approved by the FDA, can be used alone or in combination with other medications as well.

Etanercept is injected once or twice a week in the thigh, stomach or upper arm. The doctor might recommend etanercept if the disease hasn't responded to other medications or if a patient has a more advanced stage of the disease.

Research conducted since FDA approval of etanercept (Enbrel) shows that the medication has been associated with similar side effects to that of Humira.

Infliximab (Remicade) differs from the other TNF-alpha inhibitors in that it's made from human and mouse proteins rather than human-like proteins. Infliximab is given as an intravenous (IV) infusion over two or three hours rather than a self injection. A patient may receive two or three IV infusions over several weeks or months. For rheumatoid arthritis, the usual dosage schedule is three infusions over the first six weeks, then once every eight weeks after that.

Certolizumab (Cimzia) is another TNF-alpha inhibitor. It is PEGylated meaning it has a protein attachment that keeps it in the synovium (lining of the joint) longer. It is administered subcutaneously either every two or every four weeks.

Golimumab (Simponi) is another TNF-alpha inhibitor. It is administered every four weeks subcutaneously.

The TNF-alpha inhibitors have never been tested against each other, so doctors don't know if one works better than the others for rheumatoid arthritis. Studies have shown that if a patient fails one TNF-alpha inhibitor, it is still worth trying another one before moving on to a drug with a different mechanism of action.

The physician will likely also prescribe methotrexate along with all TNF-alpha inhibitors.

Common side effects of TNF-alpha inhibitors

TNF-alpha inhibitors, like many medications, carry a risk of side effects — some more serious than others. Because TNF-alpha inhibitors are infused or injected into the body, a patient might notice a reaction at the injection site. Some common signs and symptoms of injection reactions include:

• Redness
• Itching
• Pain
• Swelling
• Bleeding
• Bruising

These drugs should never be injected into skin that's tender, infected, or bruised. A different site should be used each time.

TNF-alpha inhibitors may cause other side effects:

• Runny nose
• Sneezing
• Headache
• Dizziness
• Upset stomach
• Vomiting
• Stomach pain
• Weakness
• Cough

More serious reactions to TNF-alpha inhibitors include:

•Infections. TNF-alpha inhibitors limit the body's ability to fight infections. A number of infections have been reported in people taking TNF-alpha inhibitors, ranging from upper respiratory infections to serious infections such as tuberculosis or other fungal infections. For this reason, a physician will ask about any current or recurring infections and might test for various infections. The doctor will also want to test for tuberculosis before prescribing a TNF-alpha inhibitor, as well as fungal infections such as histoplasmosis and coccidiomycosis (valley fever), since these infections may worsen and be more severe if a patient is being treated with a TNF-alpha inhibitor. If a patient develops an infection while taking these medications, they have to stop the treatment until the infection has been successfully treated.

•Lymphoma. It isn't clear whether TNF-alpha inhibitors in general cause lymphoma — some studies have found a link, while most haven't. People with rheumatoid arthritis have an increased risk of lymphoma, even without TNF-alpha inhibitor therapy. An increased risk of lymphoma has been associated with TNF inhibitors in patients with juvenile arthritis.

•Autoimmune diseases. TNF-alpha inhibitors have been associated with the development of autoimmune diseases. In rare cases people taking TNF-alpha inhibitors have been diagnosed with a condition similar to lupus.

•Neurologic and demyelinating disorders. Conditions such as myelitis, optic neuritis, Guillain-Barre syndrome, multiple sclerosis and seizure disorders have occurred in people taking TNF-alpha inhibitors.

•Blood disorders. In rare circumstances individuals taking TNF-alpha inhibitors have developed severe, sometimes fatal blood disorders.

Tociluzimab (Actemra) is an IL-6 inhibitor. IL-6 is another protein that is important in the inflammatory response. Some patients who do not respond to TNF-alpha inhibitors will respond to Actemra. Actemra is administered via intravenous infusion every month. A subcutaneous formulation is also available. Side effects are similar to that of TNF-alpha inhbitors. Actemra has also been reported to cause liver and lung abnormalities as well as bowel perforation in patients with underlying diverticular disease.

Abatacept (Orencia) is a T-cell costimulatory pathway inhibitor. That means it interferes with T-cell function. T-cells are felt to play an important role in perpetuating rheumatoid arthritis. Orencia is administered either intravenously every four weeks or subcutaneously every two to four weeks. Side effects are similar to other biologics. Patients with chronic obstructive pulmonary disease probably should not take Orencia since it seems to aggravate the condition.

Abatacept and other co-stimulation modulators render T cells inactive by interfering with the process that turns T cells on. If they don't turn on, T cells can't activate the cells that cause the inflammation and joint damage of rheumatoid arthritis.

Also people currently taking TNF-alpha inhibitors shouldn't take abatacept.

The most common side effects of abatacept include:

• Back pain
• Cough
• Dizziness
• Headache
• High blood pressure
• Nausea
• Painful hands and feet
• Rash
• Upper respiratory tract infection
• Urinary tract infection

People taking abatacept may be at an increased risk of certain cancers, including lung cancer and lymphoma, though it isn't clear why.

Rituxan is a B-cell depleter. B cells appear to also play an active role in perpetuating rheumatoid arthritis. Rituxan is not a new drug. It has been used to treat non-Hodgkins lymphoma for many years. It is given intravenously as a two doses two weeks apart, then every six months thereafter. Side effects again are similar to that of other biologic therapies with the exception of one rare but potentially lethal condition, progressive multifocal leukoencephalopathy, a severe degenerative brain disease.

JAK and SyK Kinase inhibitors will be the next wave of biologic therapies. These are small molecule drugs that can be taken orally. They have shown efficacy in rheumatoid arthritis at least as good as TNF-alpha inhibitors. Side effects include, liver and kidney dysfunction, drops in blood counts, elevated cholesterol, and hypertension.

It takes several years for drugs to move from a new idea, through research and development and, eventually, to approval. Some drugs that seemed promising in small studies won't pan out in larger clinical trials and may never receive approval. Nonetheless, the future looks bright.

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