Patients with moderately to severely
active rheumatoid arthritis experienced sustained reduction of joint pain and
swelling for as long as four years of treatment with Enbrel(R) (etanercept),
according to results from a long-term open-label study. Interim results of
this on going study are being presented at the 64th Annual Scientific Meeting
of the American College of Rheumatology by Dr. Larry Moreland of the
University of Alabama at Birmingham. These data have not been submitted to
the U.S. Food and Drug Administration.
In the study, Enbrel continues to be generally well tolerated in patients
who have received it for as long as four years. No significant differences in
the rate or type of adverse events were seen in these patients treated with
Enbrel over time. Infections resulting in hospitalization and/or treatment
with IV antibiotics observed in this study have occurred at rates similar to
those seen in controlled trials. In those controlled trials, the rates of
infection in patients receiving Enbrel and placebo were comparable. No
opportunistic infections were reported in the long-term study. There were
nine malignancies reported, of various types, similar to the number (12.7)
expected in the general population (calculated from the NCI SEER database).
Additional highlights from this long-term study of Enbrel include:
- -- At 30 months of treatment (n=300), 24 percent of patients experienced
no tender joints and 21 percent had no swollen joints.
- -- Joint improvement was rapid and sustained.
- -- Steroid use decreased in 59 percent of 337 patients. 29 percent of
patients were able to discontinue corticosteroids use, while five
percent increased steroid use.
- -- 479 patients on Enbrel have been followed for more than one year.
420 patients on Enbrel were followed for two years and 164 have been
followed for three years. Twelve patients on Enbrel were followed for
over four years. All patients in this trial had moderately to
severely active rheumatoid arthritis and had failed treatment with one
or more disease modifying anti-rheumatic drugs prior to starting
Over two million Americans suffer from the crippling effects of rheumatoid
arthritis, a chronic disorder that causes the body's immune system to attack
the lining of the joints, resulting in pain, swelling, fatigue and disability.
The exact cause of the disease is unknown although biotechnology research has
advanced understanding of the role of genes and factors causing inflammation.
The U.S. Food and Drug Administration (FDA) has approved Enbrel as a
first-line treatment of moderately to severely active rheumatoid arthritis.
Enbrel is indicated for reducing signs and symptoms and delaying structural
damage in patients with moderately to severely active rheumatoid arthritis.
In postmarketing use, serious infections and sepsis, including fatalities,
have been reported. Many of these events occurred in patients predisposed to
infections, such as those with advanced or poorly controlled diabetes.
Discontinue enbrel in patients with serious infections or sepsis. Do not
start enbrel in the presence of sepsis, infection (including chronic or
localized), or allergy to enbrel or its components. Use caution in patients
predisposed to infection.
Rare cases of central nervous system (CNS) demyelinating disorders have
been reported, although the causal relationship to Enbrel remains unclear.
Exercise caution when considering Enbrel for patients with these disorders.
Rare cases of pancytopenia, including aplastic anemia, some fatal, have been
reported in RA patients. Exercise caution in patients who have a previous
history of significant hematologic abnormalities. Although the causal
relationship to Enbrel remains unclear, advise patients to seek immediate
medical attention if they develop signs or symptoms of blood dyscrasias or
infection. If significant hematologic abnormalities are confirmed, consider
The most frequent adverse events in placebo-controlled clinical trials
(n=349) with Enbrel were injection site reactions (ISR) (37%), infections
(35%), and headache (17%). Only the rate of ISR was higher than that of
placebo. The most frequent adverse events in the methotrexate-controlled
trial (n=415) were infections (64%), ISR (34%), and headache (24%). Only the
rate of ISR was higher than that of MTX. In all RA patients treated in
clinical trials (n=1,197), malignancies were rare (1%).
Enbrel acts by binding tumor necrosis factor (TNF). TNF is one of the
dominant cytokines or proteins that play an important role in normal immune
function and the cascade of reactions that cause the inflammatory process of
RA. Enbrel competitively inhibits the binding of TNF molecules to the TNF
receptor (TNFR) sites. The binding of Enbrel to TNF renders the bound TNF
biologically inactive, resulting in significant reduction in inflammatory