New Study Supports Long-Term Use of Anti-TNF Therapy to Control Ankylosing Spondylitis

AMSTERDAM, Netherlands, June 22 /PRNewswire/ -- Data presented today at the European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology showed that use of the anti-TNF therapy infliximab over a five- year period offered effective and safe control of ankylosing spondylitis (AS), a chronic debilitating inflammatory disease. The study aimed to assess whether an anti-TNF therapy could be safely used in AS over a prolonged period of time and maintain its clinical benefit.

At the end of the five-year study, as shown in the completer analysis, nearly 60 percent of patients initially enrolled in the treatment-phase of the trial were still being given infliximab, 34.1 percent of which were in complete remission without any major side effects reported.

"This trial provides further evidence that long-term control of ankylosing spondylitis with anti-TNF therapy is possible," said Professor Jurgen Braun, M.D., lead physician at the Rheumazentrum Ruhrgebiet and Professor at the Free University of Berlin. "The results presented today should encourage rheumatologists to administer anti-TNF agents such as infliximab as on-going therapy to improve the lives of at least a third of the patients suffering from this disorder."

AS is characterized by the inflammation of joints in the spine causing a variety of debilitating symptoms including severe back pain with loss of mobility, spinal deformity and disability, peripheral arthritis and recurrent eye inflammation. A common complication of AS is the fusion of vertebrae. About 0.5 -- 1 percent of people in the European Union suffer from AS.

Study Design and Results

A total of 69 patients with active AS as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and spinal pain on a numerical rating scale had been initially enrolled in this European trial. After a three-month, placebo-controlled phase, 65 patients were entered into the open treatment phase and received 5mg/kg of IV infliximab every six weeks. Efficacy was assessed by parameters for active disease (BASDAI and levels of the inflammatory protein CRP), function (Bath Ankylosing Spondylitis Disease Functional Index - BASFI), mobility (Bath Ankylosing Spondylitis Metrology Index -BASMI), and patient (PatGA) and physician global assessments (PhysGA). Patients received infliximab for a three-year period, after which treatment was discontinued. Infliximab therapy was re-administered at the same dosage if a patient experienced a clinical relapse. Clinical remission at the end of the fifth study year was a primary outcome of the post-three year extension of the study.

Of the 69 patients enrolled in the treatment phase of the trial, 54 completed year one (FU1), 49 completed year two (FU2) and 43 patients completed year three (FU3); 41 patients (97.6 percent) completing year three were still on therapy at the completion of year five.

In analyzing the patients enrolled at the end of year five, 34.1 percent were in complete remission, as compared to 31.7 percent at FU1 and FU2, 36.6 percent at FU2 and 29.3 percent at FU3. Furthermore, 68.3 percent of patients had a 50 percent regression of their disease activity according to BASDAI as compared to baseline (FU1: 70.7%, FU2 and FU3: 65.9%). Additionally, at five years, 63.4% of Remicade-treated patients consistently reported reduced disease activity citing a 40% reduction in ASAS score (ASAS40).

  Mean efficacy scores (p<0.05) after five years were:

  --  BASDAI: 2.5+/-1.9 (baseline (BL): 6.4; FU1: 2.3; FU2 and FU3: 2.4)

  --  CRP: 3.3+/-3.8 (BL: 26.3; FU1: 3.8; FU2: 4.0; FU3: 3.1)

  --  BASFI: 3.1+/-2.4 (BL: 5.2; FU1 and FU2: 2.9; FU3: 2.8)

  --  BASMI: 2.8+/-2.1 (BL: 3.5; FU1: 2.3; FU2: 2.5; FU3: 2.6)

  --  PatGA: 2.5+/-2.2 (BL: 6.8; FU1: 2.7; FU2: 2.4; FU3: 2.5)

The clinical efficacy of infliximab persisted and no major side effects occurred during the fifth year of infliximab therapy.

Infliximab was approved by the European Union in May 2003 for the treatment of AS patients who have severe axial symptoms, elevated serological markers of inflammatory activity and who have responded inadequately to conventional therapy.

About Ankylosing Spondylitis

Ankylosing spondylitis (AS), also known as Bechterew's disease in Germany, is a painful and progressive rheumatic disease that causes arthritis of the axial skeleton (spine and sacroiliac joints) and sometimes inflammation of the peripheral joints, eyes, lungs, and heart valves. Symptoms of AS typically persist for more than three months and continue to persist for decades in the majority of patients. Symptoms include gradual onset of back pain and stiffness, which wears off during the day with light exercise, as well as pain in other areas of the body such as the buttocks or neck. According to the Arthritis Research Campaign, AS affects up to 0.5 percent of the population. On the European continent, it is estimated that prevalence ranges from 0.2 to 1 percent of the entire population.

Rheumazentrum Ruhrgebiet

The Rheumazentrum Ruhrgebiet is a highly specialized hospital for rheumatic diseases. All rheumatic diseases including inflammatory, degenerative and metabolic diseases and also fibromyalgia and osteoporosis are diagnosed and treated here. It is located in Herne, a city in the center of the Ruhrgebiet, the former main coal-mining-region in West-Germany. Founded in 1980, it currently holds 130 beds only for rheumatic diseases and is one of the greatest hospitals of its kind in Germany. Besides the in-patient treatment center, there is an efficient out-patient department. Furthermore, since 1987, it is connected with a solwater-bath which is extended to the central institution for physical therapy in the hospital. Since 2003 the center is connected with other specialties such as a large orthopedic clinic in the St. Vincenz Hospital GmbH, Herne.