Etanercept Shows Promise for Patients With Ankylosing Spondylitis

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Etanercept Shows Promise for Patients With Ankylosing Spondylitis

By Schorr

SAN FRANCISCO (MedscapeWire) Nov 15 - The drug etanercept was effective in

reducing the joint pain, stiffness, and swelling of patients with ankylosing

spondylitis, researchers reported Thursday at the 65th annual meeting of the

American College of Rheumatology.

" It's well accepted that there are limited treatment options for patients with

ankylosing spondylitis, " said lead author D. Gorman, MD, an assistant

adjunct professor of medicine in the rheumatology division at the University of

California at San Francisco. " We demonstrated that etanercept could be effective

in the treatment of moderate to severe AS. "

Researchers conducted this first study to investigate whether the drug is also

effective in patients with ankylosing spondylitis, a chronic inflammatory

disease common in young men that can cause excess bone growth and lead to spinal

deformities.

The phase II study was funded by Seattle-based Immunex Corp., the makers of the

drug by the brand name Enbrel, as well as the lind Medical Center

for Arthritis Research, the National Institutes of Health, and the Ankylosing

Spondylitis Association of America.

The single-center, double-blinded study included 40 patients with moderate to

severe disease unresponsive to standard therapy such as nonsteroidal

anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic agents

(DMARDs). The patients were predominantly white males in their late thirties and

had been living with the disease an average of 13 years.

The patients were randomly assigned to either 4 months of treatment with 25 mg

of etanercept delivered subcutaneously twice weekly, or a placebo. All the

patients also were allowed to continue on stable doses of their prior treatment,

with 90% receiving NSAIDs, 18% receiving less than 10 mg/day of prednisone, and

38% taking DMARDs.

The patients were tracked for improvement on primary outcomes of night-time

spinal pain, patients' self-assessment, the Bath AS Functional Index, duration

of morning stiffness, and swollen joint score. A response was defined as greater

than 20% improvement in 3 of 5 of these measures, without any worsening.

The researchers also measured secondary outcome measurements of symptoms such as

spinal mobility, tender and swollen joint counts, inflammatory activity,

fatigue, and quality of life.

The researchers reported that by day 112 on the drug, 80% of the patients

treated with etanercept achieved the primary endpoint of treatment response

compared with 30% of those treated with a placebo. " There was a rapid response

to etancercept which appeared to be maintained over time, " Gorman noted.

Overall, the patients on etanercept demonstrated statistically significant

improvement in all primary outcome measures, as well as secondary outcome

measures of inflammatory activity, fatigue, chest expansion, physician global

assessment, tender and swollen joint score, and the Doudados functional index.

" There was statistically significant improvement of etanercept-treated patients

in all measures of function and pain, " she noted.

For example, 72% of the patients who were treated with etanercept reported a

lessening in the duration of morning stiffness compared with none of the

placebo-treated patients. A third of the patients on etanercept reported

improvement on their patient global assessment compared with none of the

patients in the placebo group. Three-quarters of the patients on etanercept

showed an improvement in nocturnal spinal pain and sedimentation rate compared

with 18% of those who received placebo.

The researchers reported that 96% of the 117 adverse outcomes were all

classified as mild, such as injection-site reactions and infections. " The other

adverse events were mild and relatively rare, " Gorman said. " There were no

significant differences in the number of patients experiencing adverse events in

the 2 treatment groups, " Gorman said. In addition, no serious adverse events

were reported.

Immunex has announced they have begun a large, multicenter phase III clinical

study of the drug for the treatment of ankylosing spondylitis.

Etanercept, which was approved by the US Food and Drug Administration for the

treatment of rheumatoid arthritis in 1998, works by inhibiting the

overproduction of tumor necrosis factor, believed to play a major role in the

inflammatory process of the disease.