In the latest issue of the New England Journal of Medicine, two studies are published on a new class of drugs for the treatment of Rheumatoid Arthritis. Also included was an accompanying editorial, written by John H. Klippel, MD of the Arthritis Foundation, which is summarized below.

Dr. Klippel notes that:

Until now, nothing has even begun to approach the dramatic effect glucocorticoids have had in improving the care of patients with rheumatoid arthritis and other systemic inflammatory diseases...Products devised by the biotechnology industry for the treatment of rheumatoid arthritis have now been introduced into the clinic and appear to have ushered in a new era of scientifically based therapy for arthritis.

The first of these new biotechnology treatments are products that inhibit tumor necrosis factor (alpha) (TNF-(alpha)) and other biologic therapies are expected to follow.

He notes that the FDA has now approved two such drugs (etanercept and infliximab) for the treatment of rheumatoid arthritis. Etanercept is sold under the brand name of Enbrel™ and infliximab is sold under the name Remicade™.

The theory is that since TNF-(alpha) has a major role in both inflammation and bone resorption in rheumatoid arthritis, blocking the interaction between TNF-(alpha) and its receptor can provide benefit.

In addition to being approved for use in patients with rheumatoid arthritis, Enbrel has been approved for the treatment of children with polyarticular juvenile rheumatoid arthritis and infliximab for use in patients with Crohn's disease.

However, these 2 drugs are now being used "off-label" in patients with other types of chronic inflammatory and immune disorders on the assumption that TNF-(alpha) has a similar key role in those diseases as well.

As compared with methotrexate, which is considered to be the standard treatment for rheumatoid arthritis in the United States, these 2 drugs are associated with greater improvements in the symptoms and signs of arthritis and a lower risk of joint damage.

Dr. Klippel makes the assertion that "on the basis of this evidence, that TNF-(alpha) inhibitors should be used as early as possible in all patients who have documented rheumatoid arthritis," despite the fact that he acknowledges that there is no data on the long-term efficacy and safety of TNF-(alpha) inhibitors.

The drugs are also tremendously expensive at about $10,000 to $12,000 per patient per year, and the treatment must be continued for life.

Dr. Klippel also notes the apparent lack of side effects with these drugs:

TNF-(alpha) inhibitors have surprisingly few side effects. The most common are reactions at the injection site (in the case of etanercept) and hypersensitivity reactions (in the case of infliximab) and minor upper respiratory tract infections. Serious, life-threatening infections have occurred, although the exclusion of patients with chronic, recurrent, or active infections from randomized trials has markedly diminished the risk.

However, he notes that just this past month, physicians were notified that development of pancytopenia, including several cases of fatal aplastic anemia, as well as demyelinating syndromes had occurred in a small number of patients who were treated with etanercept.

"The finding of demyelinating syndromes is of interest, and perhaps not totally unexpected, since inhibition of TNF-(beta) has been associated with worsening in patients with multiple sclerosis," notes Dr. Klippel, adding that these newly surfacing risks "serve as a reminder that our understanding of the risks of inhibiting TNF-(alpha) remains incomplete."

The New England Journal of Medicine November 30, 2000; 343