BERLIN, Germany - 5 April 2002 -- For the first time, there is a therapy that can significantly reduce disease activity for the majority of patients with ankylosing spondylitis (AS), a chronic inflammatory rheumatic disease that often leads to stiffening and subsequent fusion of the spine. The study, published in the April 6 issue of "The Lancet," found more than 80 percent of patients treated with infliximab (also known as RemicadeÒ) experienced clinical improvement and more than 50 percent had their disease activity reduced by more than half.

"Treatment with infliximab, a biological medication from the new group of tumor necrosis factor alpha (TNF-a) blockers, can be regarded as a breakthrough for patients suffering from ankylosing spondylitis", emphasizes rheumatologist Prof. Dr. Jürgen Braun, lead physician at the Rheumatological Center in Herne and Professor at the Free University of Berlin. The study was conducted together with his colleagues Prof. Dr. Jochen Sieper and Dr. Jan Brandt from the Medical Clinic I, University of Benjamin Franklin, Berlin.

Unmet Medical Need

AS affects predominantly young patients, men somewhat more often than women. With no available therapies to impede the progression of the disease, patients have been limited to: 1. Alleviating pain with non-steroidal anti-inflammatory drugs; 2. Exercising to counteract stiffening; and, 3. Treating the signs and symptoms of the non-spinal arthritis that frequently accompanies AS with drugs, such as sulfasalazine.

In contrast to other rheumatic diseases, such as rheumatoid arthritis, the spinal inflammation at the center of ankylosing spondylitis has not been effectively managed. To date, cortisone preparations and immuno-modulating substances have had very little or no effect. Thus, a patient's ability to function can become significantly impaired and their quality of life reduced. As a result, the socio-economic costs are high - in part because it is a common disease.

Study Overview

The data published in The Lancet document the excellent effectiveness of infliximab for patients with active ankylosing spondylitis. TNF-a has been found in the inflamed joints of patients with AS and appears to play a significant role in the chronic inflammation associated with the disease.

Although the study was coordinated in Berlin, patients participated at eight clinics** within the Kompetenznetz Rheuma [Competency Network Rheumatology], a system of rheumatological institutions across Germany. The study is already considered a milestone in the treatment of AS because it is the first placebo-controlled study in the world with a TNF-a blocker in this disease and the initiative for the study came from the investigators and not from the pharmaceutical industry.

A total of 70 patients with active AS were registered for the study and randomized equally to receive either placebo or an infusion of infliximab 5 mg/kg at weeks 0, 2 and 6. The observation period was 12 weeks. Proven instruments for measuring disease activity, functional limitations, mobility, and the quality of life of patients with ankylosing spondylitis were used to evaluate the success of the therapy.

Treatment with infliximab led to rapid and often dramatic clinical improvement. After 12 weeks, 53 percent of patients treated with infliximab experienced at least a 50 percent reduction in disease activity compared to only 9 percent of those treated with placebo. Everyday functionality and quality of life improved significantly for those treated with infliximab but not among those taking placebo. The use of non-steroidal anti-inflammatory drugs was reduced by more than half in 56 percent of infliximab patients versus 19 percent of those treated with placebo. In addition, inflammation parameters in the blood (C-reactive proteins) dropped significantly under infliximab treatment but not under placebo.

"Although studies are difficult to compare, infliximab appears to be at least as effective if not more so for patients with ankylosing spondylitis than for patients with rheumatoid arthritis for whom the drug has already been approved", reasons Prof. Dr. Sieper, head of rheumatology at the Medical Clinic I, University of Benjamin Franklin.

*The Lancet 359; 2002:1187-93 (06.04.2002)

**Berlin-UKBF, Berlin-Charité, Berlin-Buch, Berlin-Schlosspark-Klinik, Hannover, München, Düsseldorf, Deutsches Rheuma-Forschungszentrum Berlin

Recommend Application only at Centers with Rheumatological Experience

Treatment with infliximab was well tolerated by most patients. However, relevant side effects appeared in three cases: One patient developed tuberculosis, one patient an allergic granulomatosis of the lung and another showed a temporary reduction of leucocytes (leucopoenia). All side effects were treated successfully; however, tuberculosis is, of course, a serious complication. Thus, Prof. Dr. Braun recommends tuberculosis screening prior to such a treatment and a prophylactic tuberculosis treatment if necessary. Anti-TNF therapy should only initially be used in centers with special rheumatological experience. Long-term data are not yet available, however, experts expect that the effective suppression of the inflammation with ankylosing spondylitis will also be able to prevent the dreaded stiffing of the spine.

Data and Facts Regarding Ankylosing Spondylitis

Between 0.2 and 0.9 percent of the population suffer from ankylosing spondylitis; every year, six new cases per 100,000 individuals can be expected. Men are slightly more affected than women with symptoms typically first appearing between the ages of 20 and 40, sometimes even in childhood.

The main symptom of AS is a deep-seated back pain that appears especially at night. In addition to the joints of the spine, inflammation can also attack other joints and tendons as well as the iris, heart valve, aorta, lungs or kidneys. Pain, general symptoms of the disease, and the eventual stiffening of the spine significantly impair the quality of life of the patients; in rare cases, complications may even be fatal.

The high frequency of back pain in the German population is one reason why it takes an average of six-to- eight years for a diagnosis of AS to be made. An increased effort is necessary to be in a better position to arrest the progression of the disease and the stiffening of the spine through systematic early diagnosis and new therapy.

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