Rheumatoid Arthritis - 2001 National Meeting (cont.)

Enbrel was found to be safe when used in combination with Kineret (see below).

Dr. Shiel's Perspective: Combination therapy using more than one antirheumatic drug is commonly necessary in the treatment of certain patients with RA. This combination awaits further studies of Kineret before it is used commercially.

Enbrel increases general functioning of patients with RA.

Dr. Shiel's Perspective: This is important for doctors in office practice because we want to help our patients get to their optimal functional status.

Enbrel was found to be effective in patients with juvenile RA.

Dr. Shiel's Perspective: Enbrel is already approved for the use in treating juvenile rheumatoid arthritis that has not responded to other disease-modifying rheumatic drugs.

Arava (leflunomide)

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, pyrimidine (a nucleic acid).

Arava plus methotrexate was reported as helpful and safe in patients with RA who had failed treatment with methotrexate alone. Elevations in liver function test were reversible with either a dose reduction or discontinuation of Arava.

Dr. Shiel's Perspective: This is a combination that I have not yet used. Both drugs have similar potential side effects in the liver and bone marrow.

Remicade is frequently given together with weekly methotrexate as this has previously been shown to be helpful in preventing immune reactions to the Remicade. At this meeting, papers were presented that demonstrated the safety and effectiveness of Arava in combination with Remicade as an alternative to methotrexate/Remicade combination in the treatment of RA.

Dr. Shiel's Perspective: I have already been using this combination effectively in my practice based on preliminary reports already published.

Arava was documented to be as safe after 2 years as in previously published studies of 1 year of use in patients with RA.

Arava's main side effects involve liver inflammation, skin rash, diarrhea, and reversible hair loss. Dr. Shiel's Perspective: These all seem to be relatively uncommon and seem to usually improve or resolve with adjustments of the dosage of the drug.

Arava was shown to be well tolerated and effective in treating children with RA who had failed or were intolerant of methotrexate.

Dr. Shiel's Perspective: This appears to be an important alternative it appears in juvenile rheumatoid arthritis treatment.

Kineret (anakinra)

This is the first in a new drug class that has just become commercially available for the treatment of moderate to severe RA, in patients 18 years of age or older, who have failed treatment with other disease-modifying drugs. It works by blocking the action of a chemical, interleukin-1, that is important in promoting inflammation. Kineret's safety and effectiveness has previously been documented in studies of over 1,300 patients with rheumatoid arthritis.

Kineret was shown to improve the functional status of patients with RA. In another study, Kineret was demonstrated to significantly improve the number of productive days at work and domestic home activity in patients with RA.

Dr. Shiel's Perspective: These are important because, after all, these are critical measures of successful treatment.

Kineret was found to be safe in patients when used in combination with Enbrel (see above). The safety of Kineret in over 1,100 patients was demonstrated as being similar to a placebo.

Dr. Shiel's Perspective: Combination therapy using more than one antirheumatic drug is commonly necessary in the treatment of certain patients with RA. This combination awaits further studies of Kineret before it is used commercially. Low white blood cell counts have previously been reported when combining Kineret with TNF-blocking drugs, such as Enbrel and Remicade. Kineret was also reported to reduce the inflammation of joints when used in combination with other arthritis drugs, such as indocin and methotrexate, but this was in rats. This drug appears relatively safe, but previous reports showed a small increase in infections as compared to the placebo. This drug must be injected into the skin daily. Local skin reactions (usually mild redness and irritation) at the site of the injections is the most common adverse reaction with the drug.

Kineret decreased signs of inflammatory arthritis in rats.

Dr. Shiel's Perspective: Well, this actually was a significant study because it demonstrated the beneficial effects of Kineret in reducing inflammation in the joints when used in combination with other arthritis medications, such as methotrexate.

The rate of side effects of Kineret was only slightly increased in regard to serious infections in comparison with the placebo.

Dr. Shiel's Perspective: I would like to see further side effect studies with this treatment. Preliminarily, these results are very encouraging.