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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
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