New, Targeted Therapies for Arthritis

There are many different types of rheumatological diseases. A rheumatological disease is an inflammatory arthritis that affects the entire body as a whole. Rheumatoid arthritis (RA) is the most common rheumatologic disease. Certain types of rheumatoid arthritis seem to target specific joints.

When a rheumatological disease affects the spine, the resulting conditon is called a spondyloarthropathy. The term is made up of Greek words: Spondylo means vertebra, arthro means joint and pathos means disease. When other more peripheral joints are affected (such as in the arms and legs), the rheumatologic arthritis is referred to as an spondyloarthritide.

In this article, Dr. Philip J. Mease from the Division of Rheumatology, University School of Medicine in Seattle, Washington gives us an update on two of the more common spondyloarthropathies: psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Psoriatric arthritis affects the peripheral joints. Ankylosing spondylitis affects the spine.

New findings in the field have brought these conditions and their treatment to our attention. The first major breakthrough in understanding and treating these diseases is in the area of pathophysiology. Pathophysiology tells us what went wrong at the cellular level to cause these problems.

Researchers are identifying specific differences between rheumatoid arthritis and spondyloarthropathies. Their work in the field of osteoimmunology is helping determine what's going on between the bone cells (osteo) and the immune system. This knowledge has led to more refined development of specific drug treatments for these two types of arthritis. That's good news for anyone suffering from any kind of rheumatologic disease.

For example, MRIs of patients with spondyloarthropathies show bone edema before any actual bone damage occurs in the joints. At the same time, they have found nests of lymphocytes (white blood cells), bone cells, and blood in the bone marrow (inside bones) of patients with ankylosing spondylitis. Though the exact meaining of these findings are unknown, they point in a direction to help drug manufacturers develop medications that could stop this process.

Measuring the effect of therapy on disease activity is one way to assess new treatments. Studies look at before and after outcomes of therapy on affected joints, skin, pain, function, fatigue, and quality of life. The therapeutic effects of treatment on disease activity can be difficult to measure -- especially when those changes occur at the cellular level. MRIs and X-rays may be helpful.

Patient-reported outcomes using various surveys can help track patient perceived changes, too. Some of these tools include the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Function Index (BASFI), and the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire.

Standard treatment of mild spondyloarthropathies starts with antiinflammatory drugs and topical skin creams. With more severe disease, disease modifying anti-rheumatic drugs (DMARDs) are prescribed. The most common DMARDs include methotrexate (MTX), sulfasalazine (Azulfidine), and leflunomide (Arava).

If these drugs don't reduce symptoms from disease activity, then anti-TNF agents are used. Anti-TNF stands for anti tumor necrosis factor. TNF causes inflammation. Anti-TNF turns off this response.

The most commonly used anti-TNF agents are adalimumab (Humira), entercept (Enbrel), and infliximab (Remicade). These medications usually give patients quick relief from all major rheumatologic symptoms (skin lesions, joint pain, morning stiffness, fatigue). At the same time, they have been shown effective in reducing disease activity and joint destruction.

Most of the time, doctors prescribe a single drug type (either a DMARD or an anti-TNF). But if one doesn't work, then a combination of two or more drugs are used. It may take some time to sort out which drug or drug combination works best for each individual patient. Results are measured using patient-reported outcomes, X-rays, and MRIs.

There are newer agents being studied right now. For example, Golimumab is a new anti-TNF agent that only has to be taken once a month. It's an injection that is placed just under the skin. It may be helpful for patients with psoriatic arthritis who have both skin and joint problems.

Some researchers are also investigating ways to signal immune cells to block or inhibit inflammatory cells. This type of therapy is called immunomodulation. Several of these agents are being tested in the treatment of ankylosing spondylitis.

These new and more targeted therapies may help patients who do not respond to the standard treatments used in mild to moderate disease. The ultimate goal is to prevent irreversible joint damage. The result should be less pain and better function with improved quality of life over a longer period of time for affected individuals.

Philip J. Mease, MD. Spondyloarthritis Update. In Bulletin of the NYU Hospital for Joint Diseases. 2008. Vol. 66. No. 3. Pp. 203-209.

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