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Infliximab Study Demonstrates Clinical Benefit, Sustained Efficacy in Patients With Ankylosing Spondylitis
BERLIN, June 12 /PRNewswire-FirstCall/ -- Results of the ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial demonstrated that patients with active ankylosing spondylitis (AS) treated with REMICADE® (infliximab) achieved significant improvement in signs and symptoms. More than 60 percent of patients treated with REMICADE demonstrated improvement in the ankylosing spondylitis assessment (ASAS 20) measure that includes spinal pain and function, compared with only 19 percent of patients receiving placebo. In addition, patients also experienced improvement in spinal mobility. Moreover, two sub-analyses of ASSERT showed that patients treated with REMICADE experienced improved productivity, including a reduction in missed work days, and improved quality of life. The new findings were presented today at The European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology.
"Ankylosing spondylitis is a very disabling disease and patients have few treatment options," said Professor Jurgen Braun, M.D., lead physician at the Rheumatological Center in Herne, Professor at the Free University of Berlin, and principal investigator for the ASSERT trial.
"Our findings are very encouraging for this patient population, as REMICADE demonstrated significant clinical benefits that were accompanied by improvements in health-related quality of life and, importantly a reduction in time lost from work for employed patients with AS," said Professor Desiree van der Heijde, M.D., Ph.D, University Hospital Maastricht, Maastricht, The Netherlands.
ASSERT was a Phase III, randomized, placebo-controlled, double-blind, 33-center trial in North America and Europe. The trial included 279 patients; 201 patients were treated with REMICADE and 78 patients were given placebo infusions. Patients were given REMICADE monotherapy 5 mg/kg infusions at weeks 0, 2 and 6, followed by infusions every six weeks.
The primary endpoint of the trial was the proportion of patients demonstrating a 20 percent or greater improvement in signs and symptoms as measured by the ASAS 20 at 24 weeks. Patients were assessed at baseline and at 24 weeks by standard AS performance scores. In the REMICADE group, 61 percent of patients achieved ASAS 20 compared with 19 percent of patients in the placebo group (p
In the ASSERT trial, REMICADE monotherapy was generally safe and well tolerated. Serious adverse events were reported in 4 percent of REMICADE- treated patients compared with 3 percent of patients receiving placebo. The proportion of infusions with infusion reactions was the same for both treatment groups (3 percent). No deaths, malignancies or tuberculosis cases were reported in this study (please see "Important Information" below).
Results of ASSERT Sub-analyses
An analysis was conducted in a subset of 122 patients who were employed full-time both at baseline and week 24. Productivity was assessed using a visual analog scale, and the number of workdays missed was collected at each visit. Workdays missed during the six weeks before baseline were compared with those missed during the six weeks before week 24. The median percent change from baseline in the productivity score in the REMICADE group was 62 percent (p
In another ASSERT analysis, health-related quality of life (HRQOL) was assessed using the change from baseline in the eight Short Form-36 scales as well as the 2 summary scores in the SF-36. Patients on REMICADE had significantly greater improvements from baseline at week 24 than did patients on placebo on physical functioning, bodily pain and general health.
Separately, data from another trial were presented at EULAR demonstrating three-year sustained efficacy with REMICADE in AS. These data were presented as an extension to the controlled trial, which supported the approval for REMICADE in AS in the European Union. "These data are important as they demonstrate continued benefit to those patients treated with REMICADE after three years of therapy," said Professor Jurgen Braun, M.D., lead physician at the Rheumatological Center in Herne, Professor at the Free University of Berlin and investigator.
REMICADE is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies and is the only biologic indicated for the treatment of both rheumatoid arthritis (RA) and Crohn's disease (CD) in North America, the European Union and Japan. In May 2003, REMICADE was approved in the European Union for the treatment of AS, making it the first biologic to receive approval from a major regulatory authority for this indication. Centocor is seeking approval for the use of REMICADE in the treatment of AS in the United States and a supplemental Biologics License Application (sBLA) is under review by the Food and Drug Administration (FDA). REMICADE is currently approved for the treatment of AS in 48 countries.
About Ankylosing Spondylitis
AS is a painful and progressive form of spinal arthritis that typically begins in the late teens and early twenties and can result in fusing of the spinal vertebrae, hips and other joints. Often misdiagnosed as "just back pain" or undifferentiated arthritis, AS is a systemic inflammatory disease that in addition to its effect on the spine, can affect vision, internal organs, and peripheral joints. According to the Arthritis Research Campaign, AS affects up to 0.5 percent of the population.(1) On the European continent, it is estimated that prevalence ranges from 0.2 to 1 percent of the entire population.(2) The Spondylitis Association of America (SAA) estimates that between 350,000 and one million people in the United States suffer from AS or a related disease.
REMICADE is a monoclonal antibody that specifically targets and irreversibly binds to tumor necrosis factor-alpha (TNF-alpha) on the cell membrane and in the blood. Overproduction of TNF-alpha is believed to play a role in ankylosing spondylitis (AS), rheumatoid arthritis (RA), a chronic, debilitating inflammatory disease that causes pain, swelling, stiffness and loss of function in the joints and Crohn's disease (CD), a serious gastrointestinal disorder, in addition to a wide range of Immune-Mediated Inflammatory Disorders (I.M.I.D.) in which REMICADE is currently being studied.
REMICADE is the only anti-TNF biologic therapy that has received marketing authorizations for the treatment of both RA and CD and, in the European Union, AS. In most countries where it has received marketing authorization, REMICADE, in combination with methotrexate, is indicated for the treatment of patients with moderately to severely active RA who have had an inadequate response to methotrexate alone. REMICADE is the only biologic indicated for the treatment of patients with moderately to severely active CD who have had an inadequate response to conventional therapy. REMICADE is also indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in patients with fistulizing CD. In addition, in the European Union, REMICADE is indicated for the treatment of ankylosing spondylitis in patients who have severe axial symptoms, elevated serological markers of inflammatory activity and who have responded inadequately to conventional therapy.
REMICADE is unique among available anti-TNF biologic therapies. Unlike self-administered therapies that require patients to inject themselves frequently, REMICADE is the only anti-TNF biologic administered directly by caregivers in the clinic or office setting. In RA and CD patients, REMICADE is typically received every eight weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6. As a result, REMICADE patients may require as few as six treatments each year. The safety and efficacy of REMICADE has been well established in clinical trials conducted over the past 10 years and through commercial experience with now more than 500,000 patients treated worldwide.(3)
Many people with heart failure should not take REMICADE; so, prior to treatment you should discuss any heart condition with your doctor. Tell your doctor right away if you develop new or worsening symptoms of heart failure (such as shortness of breath or swelling of your ankles or feet).
There are reports of serious infections, including tuberculosis (TB) and sepsis. Some of these infections have been fatal. Tell your doctor if you have had recent or past exposure to people with TB. Your doctor will evaluate you for TB and perform a skin test. If you have latent (inactive) TB your doctor should begin TB treatment before you start REMICADE. If you are prone to or have a history of infections, currently have one, or develop one while taking REMICADE, tell your doctor right away. Also tell your doctor if you have lived in a region where histoplasmosis or coccidioidomycosis is common or if you have or have had a disease that affects the nervous system, or if you experience any numbness, weakness, tingling, or visual disturbances.
There are also reports of serious infusion reactions with hives, difficulty breathing, and low blood pressure. In clinical studies, some people experienced the following common side effects: respiratory infections (that may include sinus infections and sore throat), coughing, and stomach pain or mild reactions to infusion such as rash or itchy skin. Please read important information about REMICADE, as described in the full US prescribing information, at http://www.remicade.com/. For a complete copy of REMICADE E.U. prescribing information, please contact Schering-Plough at + 1-908-298-7616.
References: 1. Arthritis Research Campaign Available at Arthritis Research Campaign. Available at http://www.arc.org.uk/newsviews/arctdy/105/ankyspon.htm. Accessed on March 22, 2004. 2. Orphanet. Available at http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=825. Accessed on March 24, 2004. 3. Data on File at Centocor
Source: Centocor, Inc.; Schering-Plough Europe