Reports From National Arthritis Meeting

Dr. Shiel Gives Perspectives Of Interest On Psoriatic Arthritis and Ankylosing Spondylitis From 2001 Annual Scientific Meeting Of The American College Of Rheumatology

• Introduction
• Medications
• Bowel Disease (Ulcerative Colitis & Crohn's Disease)
• Genetics

Introduction

Psoriatic arthritis is a chronic disease that is characterized by inflammation of the skin (psoriasis) and joints (arthritis). Psoriasis is a common skin condition that affects 2% of the Caucasian population in the United States. It is often characterized by patchy, raised, red areas of skin inflammation with scaling. Psoriasis often affects the tips of the elbows and knees, the scalp, the navel, and around the genital areas or anus. Approximately 10% of patients who have psoriasis also develop an associated inflammation of their joints. Patients who have arthritis and psoriasis are diagnosed as having psoriatic arthritis.

Ankylosing spondylitis is a form of chronic inflammation of the spine and the sacroiliac joints. The sacroiliac joints are located in the low back where the sacrum (the bone directly above the tailbone) meets the iliac bones (bones on either side of the upper buttocks). Chronic inflammation in these areas causes pain and stiffness in and around the spine. Over time, chronic spinal inflammation (spondylitis) can lead to a complete cementing together (fusion) of the vertebrae, a process called ankylosis. Ankylosis causes total loss of mobility of the spine.

Ankylosing spondylitis and psoriatic arthritis are genetically and clinically related diseases. I will, therefore, report on papers presented at this meeting related to both of the diseases here.

Medications

Remicade (infliximab)

Remicade (infliximab) is an antibody that blocks the effects of tumor necrosis factor alpha (TNF-alpha). TNF- alpha is a substance made by cells of the body that has an important role in promoting inflammation. By blocking the action of TNF-alpha, infliximab reduces the signs and symptoms of inflammation. Remicade is infused into a vein in the arm, usually every 2 months.

Remicade was reported as effective for treating psoriatic arthritis and ankylosing spondylitis. For those with psoriasis, Remicade not only helped the arthritis, but also helped to clear the psoriasis, often dramatically. A number of papers not only documented the effectiveness and safety of Remicade, but also showed how it gets prompt results and improved the quality of life for these patients.

Dr. Shiel's Perspective: A welcome addition to treatment options that have been sorely lacking for these diseases. (I have actually been treating patients with these diseases very effectively with Remicade for some time now based on preliminary data reported at previous meetings.)

Remicade was found to be effective in much higher than the recommended doses.

Dr. Shiel's Perspective: This is similar to findings in patients with rheumatoid arthritis. That is, many times we must increase the doses above the starting doses to get the best results.

Remicade was also reported as effective in treating psoriasis and psoriatic arthritis in patients who had previously failed methotrexate or Enbrel.

Dr. Shiel's Perspective: This is consistent with recent reports of the effectiveness of Remicade in treating rheumatoid arthritis.

Remicade was shown to be extremely beneficial in the treatment of plaque-type psoriasis.

Dr. Shiel's Perspective: This was a fine study of 33 patients and documents not only the clinical benefit of Remicade alone in the treatment of this common form of psoriasis, but also its rapid onset of response of the inflamed skin to the drug.

Enbrel (etanercept)

Enbrel is an injectable anti-tumor necrosis factor for treating rheumatoid arthritis. Tumor necrosis factor (TNF) is a protein that the body produces during the inflammatory response, which is the body's reaction to injury. TNF promotes the inflammation and its associated fever and signs (pain, tenderness, and swelling) in several inflammatory conditions, including psoriatic arthritis and ankylosing spondylitis . Enbrel is a synthetic (man-made) protein that binds to TNF. Enbrel thereby acts like a sponge to remove most of the TNF molecules from the joints and blood. This prevents TNF from promoting inflammation and the fever, pain, and tenderness and swelling of joints in patients with psoriatic arthritis and ankylosing spondylitis. Enbrel is injected into the skin twice weekly.

Enbrel was reported as effective for treating psoriatic arthritis and ankylosing spondylitis. For those with psoriasis, Enbrel not only helped the arthritis, but also helped to clear the psoriasis, often dramatically. In those treated with Enbrel, there were no serious unforeseen side effects.

Dr. Shiel's Perspective: A welcome addition to treatment options that have been sorely lacking for these diseases.

Enbrel-treated patients were able to mount a normal immune response to Pneumococcal vaccine.

Dr. Shiel's Perspective: This is significant in that it demonstrates that while TNF-blocking could theoretically increase the infection rate by impeding the immune system, at least the antibody-producing branch of the immune system is functional.

Two papers documented the effectiveness and safety of Enbrel in the treatment of ankylosing spondylitis in children (juvenile ankylosing spondylitis).

Dr. Shiel's Perspective: These are important papers that will open up options of treatment for this rare disease of children, even children under the age of 4 years, according to one of the studies.

Arava

Arava reduces inflammation by suppressing the immune cells responsible for the inflammation. It does this by preventing the formation of DNA and RNA in the immune cells by inhibiting an enzyme (dihydroorotate dehydrogenase) that is necessary for the production of a critical component of DNA and RNA called pyrimidine (a nucleic acid). The drug has traditionally been used to treat rheumatoid arthritis.

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Arava was reported as beneficial and well tolerated as a treatment for psoriatic arthritis in a study reported from Italy. Another study from Illinois demonstrated the effectiveness of Arava in treating both psoriasis and psoriatic arthritis.

Dr. Shiel's Perspective: These are preliminary studies with a small number of patients (six and twelve). More studies are needed to verify these encouraging results.

Alefacept

Alefacept is an experimental drug that is not commercially available. Alefacept was given intravenously weekly for 12 weeks to 11 patients with psoriatic arthritis. It was found to improve joint symptoms and reduce the psoriasis.

Dr. Shiel's Perspective: This is a very preliminary study. I feel its primary interest lies in the fact that psoriasis and psoriatic arthritis are both significantly affected by T cell action. This drug blocks T cell activation and this likely explains its effects. While this report is encouraging, more studies will be required to verify the drug's safety and effectiveness of treatment in larger numbers of patients.

Bowel Disease (Ulcerative Colitis & Crohn's Disease)

The inflammatory bowel diseases, ulcerative colitis and Crohn's disease, are genetically related to ankylosing spondylitis and psoriatic arthritis. It is not unusual for patients to have features of any combination of these conditions.

A study from England documented that the inflammatory bowel disease may not present for an average of 8 years after the initial symptoms of ankylosing spondylitis. HLA-B27 gene was present in 91% of ankylosing spondylitis patients. In patients with both ankylosing spondylitis and ulcerative colitis, the HLA-B27 gene was present in 81% and ankylosing spondylitis with Crohn's disease in 72%.

Dr. Shiel's Perspective: This is a very helpful paper for doctors and those affected by ankylosing spondylitis. Both should be vigilant for the symptoms of inflammatory bowel disease, such as abdominal cramping, chronic diarrhea, and pus or blood in the stools. If these symptoms occur, even years after the onset of spinal inflammation, a further evaluation of the bowels may be needed.

Genetics

The determinants of the severity of ankylosing spondylitis have been isolated to only a few genes.

Dr. Shiel's Perspective: This very difficult (and technical) study implies that this disease is dominated by the effects of an isolated number of genes (DNA material that codes for proteins involved in expressing the disease). It will likely lead to more accurate treatments in the future.

For more information, please visit www.MedicineNet.com's Psoriatic Arthritis and Ankylosing Spondylitis Centers in the Diseases and Conditions area.