Trial of Etanercept for Wegener¹s Disease Shows No Benefit Against the Autoimmune Condition

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Trial of Etanercept for Wegener¹s Disease Shows No Benefit Against the

Autoimmune Condition

Description

A s Hopkins-led study designed to evaluate the ability of etanercept to

maintain disease remissions in a serious autoimmune disorder has failed to

show any benefit. Etanercept, also called Enbrel, is a common treatment for

rheumatoid arthritis and other types of joint inflammation.

Newswise ‹ A s Hopkins-led study designed to evaluate the ability of

etanercept to maintain disease remissions in a serious autoimmune disorder

has failed to show any benefit. Etanercept, also called Enbrel, is a common

treatment for rheumatoid arthritis and other types of joint inflammation.

³We had hoped that this approach to the treatment of Wegener¹s

granulomatosis would be useful in preventing disease relapses,² says H.

Stone, M.D., associate professor of medicine, director of the s Hopkins

Vasculitis Center, and lead investigator of the study published in the Jan.

27, 2005, issue of the New England Journal of Medicine.

³The study results, however, demonstrate unequivocally that etanercept was

not effective for this purpose. Because of the disease¹s propensity to flare

following remission and the high risk of treatment complications associated

with conventional therapies for Wegener¹s, we must continue to look for

safe, effective ways of achieving and maintaining disease remissions,² said

Stone.

Wegener¹s granulomatosis is an uncommon disorder in which the body¹s immune

system attacks its own blood vessels, damaging vital organs by limiting the

flow of blood to lungs, kidneys, upper airways and other organs. The disease

can affect people of any age and occurs in men and women with equal

frequency.

Although current medications used to treat Wegener¹s halt the disease

temporarily in most patients, 60 to 80 percent of patients eventually suffer

from disease flares. The need to treat many patients repeatedly with

medications such as glucocorticoids (prednisone), cyclophosphamide, and

methotrexate leads to mounting morbidity from treatments. At the same time,

each disease flare has the potential to cause irreversible damage. Wegener¹s

granulomatosis frequently leads to kidney failure, hearing loss, damage to

the respiratory tract, peripheral nerve injury, and other complications,

according to Stone.

Etanercept, the first of a class of drugs called tumor necrosis factor

inhibitors approved by the U.S. Food & Drug Administration for the treatment

of rheumatoid arthritis, is also known to be effective in psoriasis,

psoriatic arthritis, and juvenile rheumatoid arthritis. To test the

effectiveness of etanercept at preventing flare-ups for Wegener¹s patients,

Stone and colleagues from seven other academic medical centers enrolled 180

patients with the disease into a randomized, placebo-controlled clinical

trial. All patients received standard drug therapy to treat the disease. In

addition to standard therapies, 89 patients received etanercept and 91

received placebo. Patients were followed for an average of 27 months.

The researchers found no significant differences in the percentages of

patients in the two groups who achieved disease remissions of at least six

months duration: 69.7 percent among the etanercept-treated patients,

compared with 75.3 percent in the control group. In the trial overall, fewer

than 50% of the patients achieved and maintained remissions for the duration

of the study. There were also no differences between groups in the numbers

of patients who experienced severe or limited disease flares. Twenty-three

patients in the etanercept group suffered severe flares during the trial,

for example, compared with 25 in the comparison group. In both groups,

disease remissions were achieved at a high cost in treatment-associated

adverse effects. Most side effects of treatment were attributed to

conventional medications. Solid cancers developed in six patients in the

etanercept group, however, compared with none in the placebo group.

³The number of malignancies observed is too small to draw any firm

conclusions,² noted Stone. ³There is certainly the potential for interaction

between TNF inhibitors and cyclophosphamide - a drug known to cause several

types of cancer. This potential association bears further scrutiny,² said

Stone.

Other centers participating in the study were the Beth Israel Medical Center

(New York), Boston University, the Cleveland Clinic Foundation, Duke

University, the University of California, San Francisco, the Mayo Clinic,

and the University of Michigan. The study was funded by the National

Institute of Arthritis, Musculoskeletal, and Skin Diseases/National

Institutes of Health (NIH/NIAMS) and the Office for Orphan Products

Development (U.S. Food and Drug Administration). Amgen Corporation provided

etanercept and placebo for the trial.

On the Web:

http://www.nejm.org

http://vasculitis.med.jhu.edu/index.html