Remicade

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Not sure if this had been posted before, but thought I would post it in case it

had not been.

Mark

" X-RAY STUDY SUGGESTS REMICADE STOPS PROGRESSION OF RHEUMATOID ARTHRITIS

BOSTON,

Nov 15, 1999 /PRNewswire via COMTEX/ -- REMICADE (infliximab) in combination

with methotrexate appeared to stop progression of rheumatoid arthritis (RA) in

clinical trial patients, according to radiographic (x-ray) data presented here

today at the annual meeting of the American College of Rheumatology.

These findings from a controlled clinical trial are among the first to suggest

that a drug can halt damage caused by rheumatoid arthritis, a chronic and

debilitating disease that affects more than 2.5 million Americans.

" For decades, rheumatologists have searched for a medical therapy that can

actually stop progression of rheumatoid arthritis. The data from this clinical

trial could revolutionize the field of rheumatology, " said Lipsky,

M.D.(1), who was co-chairman of the Phase III ATTRACT (Anti-TNF Trial in

Rheumatoid Arthritis with Concomitant Therapy) trial while director of the

Harold C. Arthritis Research Center at the University of Texas

Southwestern Medical Center in Dallas.

Dr. Lipsky presented the one-year x-ray findings from ATTRACT at a symposium

titled " Changing the Management of Rheumatoid Arthritis. "

X-Ray Results Positive for All REMICADE-treated Patients at Six Months and One

Year

In this study, prevention of structural damage was assessed using a modified

Sharp score, which evaluates a combination of bone erosion and joint- space

narrowing on a scale of 0-4 (higher score indicates more damage).

The data presented today found no median progression of joint damage from

baseline (0.0 score) among all patients (n=285) treated with the combination of

REMICADE plus methotrexate compared to patients (n=63)

treated with methotrexate alone (4.0 score). Year-one radiographic results

found considerable progression of joint damage in patients receiving

methotrexate alone.

The methotrexate-only findings (control arm) represent a 7-to-8 percent

deterioration in radiographic scores, which is comparable to that previously

reported for patients with established rheumatoid arthritis treated with

disease-modifying anti-rheumatic drug therapy, including methotrexate.

Methotrexate is a standard treatment for rheumatoid arthritis.

Of those enrolled in the trial, 348 were included in the primary analysis.

X-rays were taken of each patient at baseline, week 30 (30W)

and week 54 (54W). Two experienced readers, who were blinded to patients and

treatment arms, evaluated every x-ray. Each patient's x-rays (baseline, 30W and

54W) were presented simultaneously and in random order, and each reader

individually calculated modified Sharp scores.

The primary endpoint was the median change from baseline for each patient

averaged between two readers.

Study Overview X-ray data are from the one-year radiographic results of ATTRACT,

one of the largest studies ever conducted in patients with advanced rheumatoid

arthritis. ATTRACT is a double blind, placebo-controlled, randomized clinical

trial of 428 patients at 34 clinical sites in North America and Europe. Four

dosing regimens of REMICADE plus methotrexate were compared to methotrexate

alone (control).

The median duration of disease in trial patients was 8.4 years, and all patients

were on methotrexate therapy with the majority for three or more years. More

than one-third of all patients had previous joint surgery, and approximately one

half were classified as functional class

3 or 4, which indicates progressive and advanced disease. All patients were on

stable doses of concomitant methotrexate, corticosteroids and nonsteroidal anti-

inflammatory drugs.

" One of the most stunning aspects of this data is that patients treated with

REMICADE plus methotrexate achieved positive joint damage x-ray results

regardless of whether they experienced relief from the signs and symptoms of the

disease, " said Ravinder Maini, M.D., scientific director, Kennedy Institute of

Rheumatology in London and co-chairman of ATTRACT with Dr. Lipsky.

" The REMICADE data presented today suggest the need to establish new outcome

measures for assessment of all therapies for rheumatoid arthritis. "

Based on ATTRACT radiography data, Centocor, Inc. submitted in October a

supplemental Biologics License Application (sBLA) to the Food and Drug

Administration (FDA) seeking approval for the prevention of joint damage in

patients with rheumatoid arthritis.

If this submission is cleared for marketing, REMICADE would be the first agent

in a new class of drugs known as joint-damage arresting anti-rheumatic therapies

(JDAART).

REMICADE Generally Well Tolerated in ATTRACT The most common adverse events in

the ATTRACT trial included upper respiratory tract infections, headache, nausea,

sinusitis, rash and cough. There was no increased incidence of serious adverse

events (11 percent with REMICADE and methotrexate vs. 16 percent with

methotrexate alone) or serious infections (four percent with REMICADE plus

methotrexate vs. six percent with methotrexate alone).

The incidence of infusion reactions was also low in REMICADE plus methotrexate

patients (five percent) compared to those receiving methotrexate alone (two

percent).

Tumor necrosis factor-alpha (TNF-alpha) mediates inflammation and cellular

immune response including response to infection. Serious infections, including

sepsis and fatal infections, have been reported in patients receiving

TNF-blocking agents. Many of the serious infections in patients treated with

REMICADE have occurred in patients on concomitant immunosuppressive therapy

that, in addition to their Crohn's disease or rheumatoid arthritis, could

predispose them to infections.

Patients treated with REMICADE may have an increased risk of infection.

Caution should be exercised when considering the use of REMICADE in patients

with chronic infection or a history of recurrent infection.

REMICADE should not be given to patients with a clinically important, active

infection.

Patients who develop a new infection while undergoing treatment with REMICADE

should be monitored closely. If a patient develops a serious infection or

sepsis, REMICADE therapy should be discontinued. Please see www.remicade.com

for full prescribing information and additional information regarding warnings,

precautions and adverse events.

ABOUT RHEUMATOID ARTHRITIS Approximately 2.5 million Americans -- mostly women

-- suffer from rheumatoid arthritis, which is a chronic and often painful

disease characterized by inflammation of the joints. Its initial symptoms

include fatigue, joint pain and anemia. As the disease progresses, joints

become swollen, inflamed and stiff.

Rheumatoid arthritis usually begins with the hands, wrists, feet, knees and

elbows, but often also attacks the shoulders, neck, hips and ankles.

When inflammation persists or does not respond well to treatment, destruction of

nearby cartilage, bone, tendons and ligaments can occur and lead to permanent

disability. This often occurs despite current therapy.

Many patients with rheumatoid arthritis will become physically disabled due to

the joint erosion that occurs as the disease progresses. In fact, according to

the American College of Rheumatology, 50 percent of patients with rheumatoid

arthritis will be unable to work within 10 years of their initial diagnosis.

ABOUT REMICADE REMICADE reduces inflammation in patients with Crohn's disease

and rheumatoid arthritis by binding to and neutralizing TNF-alpha on the cell

membrane and in the blood. TNF-alpha is a key inflammatory mediator, or

cytokine, in rheumatoid arthritis, Crohn's disease and other autoimmune

disorders. Overproduction of TNF-alpha leads to inflammation in these chronic

conditions.

A pioneer of TNF-alpha inhibitor technology, Centocor is among the world's

leading producers of monoclonal antibodies for therapeutic use.

On November 10, 1999, the FDA approved REMICADE, in combination with

methotrexate, for the reduction of signs and symptoms of rheumatoid arthritis in

patients who have had an inadequate response to methotrexate. In the United

States, REMICADE is co-marketed by Centocor and Ortho-McNeil Pharmaceutical,

Inc., both & subsidiaries, for rheumatoid arthritis.

REMICADE is also commercially available in the United States and Europe for use

in patients with Crohn's disease, a serious gastrointestinal disorder.

Centocor, based in Malvern, Pa., manufactures REMICADE.

Schering-Plough Corporation has rights to market REMICADE in all other countries

throughout the world, except in Japan and parts of the Far East where REMICADE

will be marketed by Tanabe Seiyaku, Ltd. In August

1999, a centralized Type II variation was submitted to the European Agency for

the Evaluation of Medicinal Products seeking clearance to market REMICADE for

the treatment of rheumatoid arthritis.

(1) Dr. Lipsky is scientific director of the Intramural Research Program at the

National Institute of Arthritis and Musculoskeletal and Skin Diseases at the

National Institutes of Health in Bethesda, Md. The views expressed by Dr.

Lipsky in this release do not necessarily represent those of the National

Institutes of Health or the U. S. Department of Health and Human Services.

SOURCE Centocor, Inc.