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New MRI Data Shows Remicade(R) Significantly Decreases Spinal Inflammation in Patients With Ankylosing Spondylitis

Posted on: Tuesday, 19 October 2004, 12:00 CDT

Results of the ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial demonstrated that patients with active ankylosing spondylitis (AS), a form of spinal arthritis, treated with REMICADE(R) (infliximab), had a median decrease of 73 percent in spinal inflammation activity scores at 24 weeks of treatment, while patients receiving placebo showed no effect as measured by magnetic resonance imaging (MRI). It has been hypothesized that if inflammation persists and is left untreated, loss of spinal mobility and structural damage to the spine may result. The study included the largest number of patients with AS ever evaluated for spinal inflammation using MRI (n=266). MRI provides the ability to observe inflammation and erosions in the spine in AS. The new findings will be presented this week at the American College of Rheumatology (ACR) 68th Annual Scientific Meeting.

"Previous findings showed that REMICADE provided improvement in spinal pain and spinal mobility associated with AS while improving physical function," said Professor Juergen Braun, M.D., lead physician at the Rheumatological Center in Herne, professor at the Ruhr-Universitaet of Bochum, and principal investigator for the ASSERT trial. "These new data suggest that REMICADE is effective in reducing spinal inflammation, and by its effect on inflammation, may lessen the subsequent structural changes associated with ankylosing spondylitis."

Centocor is seeking approval for REMICADE in ankylosing spondylitis and has previously announced that the U.S. Food and Drug Administration (FDA) has accepted its supplemental Biologics License Application (sBLA) for the use of REMICADE(R) for the treatment of AS, a chronic, progressive and debilitating inflammatory disease that often leads to stiffening and subsequent fusion of the spine. REMICADE is currently approved for the treatment of AS in 57 countries.

The U.S. submission for AS was based primarily on the 24-week results of the ASSERT trial, which showed that patients with active AS achieved improvement in signs and symptoms associated with their disease, including reduced spinal pain, increased physical function and increased health-related quality of life when treated with REMICADE. Patients in the ASSERT trial will be followed through 102 weeks, and further analyses will evaluate the structural damage benefit.

Results from the ASSERT Analysis

The purpose of this secondary analysis from ASSERT was to compare the effect of infliximab on active spinal inflammation versus placebo as measured by MRI. A total of 194 patients (97 percent) in the infliximab group and 72 patients (92 percent) in the placebo group had evaluable images. MRI images of the spine were acquired at baseline and at week 24. Images were scored according to a method in which inflammation (with or without erosions) was measured at 23 vertebral units from C2 to S1, resulting in an inflammation activity score for each patient ranging from 0 to 138. At week 24, the median change from baseline in activity score in the infliximab group was -2.72 compared with 0.00 in the placebo group (p < 0.001) representing a median decrease of 73 percent in spinal inflammation score in the infliximab group versus 0 percent in the placebo group.

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 peripheral joints, internal organs and vision. 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. On the European continent, it is estimated that prevalence ranges from 0.2 to 1 percent of the entire population(1).

About ASSERT

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 < 0.001). Clinical benefit was observed in patients receiving REMICADE as early as week 2 and was maintained over the 24-week study period. In the REMICADE group, 22 percent of patients met the criteria for ASAS major clinical response compared with 1 percent in the placebo group (p < 0.001). Patients receiving REMICADE also showed significant improvements in individual measurements of disease activity, function, and mobility, as well as improvements in chest expansion, reduction in night pain and patient global assessment.

In the ASSERT trial, REMICADE monotherapy was generally safe and well tolerated. The most commonly reported adverse events were upper respiratory tract infections, which occurred at a slightly higher rate in the placebo group (15 percent) compared to the infliximab group (14 percent). Serious adverse events were reported in 4 percent of REMICADE-treated patients compared with 3 percent of patients receiving placebo. Please read the important information below.

Important Information

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. REMICADE can lower your ability to fight infections, so if you are prone to or have a history of infections, or develop any signs of an infection such as fever, fatigue, cough, or the flu 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. Blood disorders have been reported, some fatal. Tell your doctor if you develop possible signs of blood disorders such as persistent fever, bruising, bleeding, or paleness while taking REMICADE. Nervous system disorders have also been reported. Tell your doctor if you have or have had a disease that affects the nervous system, or if you experience any numbness, weakness, tingling, or visual disturbances while taking REMICADE. Reports of lymphoma (a type of cancer) in patients on REMICADE and other TNF blockers are rare but occur more often than in the general population. Tell your doctor if you have or have had cancer.

Serious infusion reactions have been reported with REMICADE, including hives, difficulty breathing, and low blood pressure. Reactions have occurred during or after infusions. 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, including full prescribing information, at www.remicade.com.

About REMICADE

REMICADE is a monoclonal antibody that specifically targets and binds to tumor necrosis factor-alpha (TNF-a) on the cell membrane and in the blood. Overproduction of TNF-a is believed to play a role in rheumatoid arthritis (RA); ankylosing spondylitis (AS), a form of spinal arthritis; Crohn's disease (CD), a serious gastrointestinal disorder; and psoriatic arthritis (PsA), a disease that includes symptoms of both psoriasis and rheumatoid arthritis, 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 global market leader among anti-tumor necrosis factor alpha (TNF-a) therapies and the only agent approved for the treatment of both RA and Crohn's disease in North America, the European Union and Japan, and was the first biologic approved for ankylosing spondylitis in the European Union. In the EU, 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.

This month, the European Union Committee for Medicinal Products for Human Use of the European Agency for the Evaluation of Medicinal Products (EMEA) gave approval of expanded labeling for REMICADE (infliximab), in combination with methotrexate, for treatment of active and progressive psoriatic arthritis (PsA) in patients who have responded inadequately to disease modifying anti-rheumatic drugs. In RA, in the EU, REMICADE, in combination with methotrexate, is indicated for the reduction of signs and symptoms as well as the improvement in physical function in patients with active disease when the response to disease modifying drugs, including methotrexate, has been inadequate, and in patients with severe, active and progressive disease not previously treated with methotrexate or other DMARDs. In these patient populations, a reduction in the rate of the progression of joint damage, as measured by X-ray, has been demonstrated.

In the U.S., REMICADE in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis. REMICADE is the only biologic indicated for the treatment of patients with moderately-to-severely active Crohn's disease 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 Crohn's disease.

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, REMICADE is a two-hour infusion administered 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. In the EU, in AS, REMICADE is a two-hour infusion (5 mg/kg) administered every 6 weeks, following a standard induction regimen that requires treatment at weeks 0, 2, and 6. The safety and efficacy of REMICADE have been well established in clinical trials over the past 12 years and through commercial experience with over a half million patients treated worldwide(2).

About Centocor

Centocor is a leading biopharmaceutical company that creates, acquires and markets cost-effective therapies that yield long-term benefits for patients and the healthcare community. The company is dedicated to the research and development of treatments for a wide range of diseases including cancer, infectious diseases, cardiovascular and metabolic diseases and Immune-Mediated Inflammatory Disorders (I.M.I.D.), such as arthritis and inflammatory skin diseases. Centocor's products, developed primarily through monoclonal antibody technology, help physicians deliver innovative treatments to improve human health and restore patients' quality of life. Centocor is a wholly owned subsidiary of Johnson & Johnson, the worldwide manufacturer of healthcare products.

Centocor discovered REMICADE and has exclusive marketing rights to the product in the United States. Schering-Plough Corporation has rights to market REMICADE in all countries outside of the United States, except in Japan and parts of the Far East where Tanabe Seiyaku, Ltd. markets the product.

References:

(1) Orphanet. Available at http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=825. Accessed on March 24, 2004.

(2) Data on File at Centocor

Abstract: The Effect of Infliximab Therapy on Spinal Inflammation Assessed by Magnetic Resonance Imaging in a Randomized, Placebo-controlled Trial of 279 Patients with Ankylosing Spondylitis

Author: Braun, et al.

Date: Thursday, October 21, 2004

Time: 10:15 a.m. to 10:30 a.m.

Location: Ballroom A

 CONTACT: Michael Parks Centocor, Inc. Phone:  (215) 325-4010 Mobile:  (610) 216-3965  

SOURCE: Centocor

Source: MARKET WIRE

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