Washington, D.C. -- July 12, 2000 Centocor, Inc. said today that the Arthritis Advisory Committee to the U.S. Food and Drug Administration (FDA) voted unanimously to recommend approval of REMICADE® (infliximab) with methotrexate for reduction of structural damage in patients with rheumatoid arthritis. REMICADE with methotrexate is currently approved for treatment of rheumatoid arthritis in patients who have an inadequate response to methotrexate alone. Rheumatoid arthritis affects approximately 2.5 million Americans, mostly women.
In patients with rheumatoid arthritis, joint damage is caused by narrowing of the space between connecting bones, as well as erosions to bones.
"To reduce joint damage in patients with rheumatoid arthritis, a drug must have an effect on both joint space narrowing and bone erosions. Based on the clinical data, it appears that REMICADE does both, with compelling results," said Harlan F. Weisman, M.D., senior vice president, research and development, Centocor. "Furthermore, the data suggest that treatment with REMICADE improved a patient¹s ability to do the everyday tasks that most of us take for granted."
A study by Fred Wolfe, MD and John Sharpe, MD, in Arthritis and Rheumatology (1998; 41(9):1571-1582) showed that joint damage in rheumatoid arthritis progresses at a steady rate over time despite treatment with standard disease modifying anti-rheumatic drugs. A therapy with the ability to stop this steady rate of progression could have an important impact on the natural history of the disease, Weisman continued.
The committee reviewed a presentation of radiographic (x-ray) data from the large, multi-center, Phase III ATTRACT trial (Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy). In the ATTRACT study, progression of joint damage was radiographically measured as changes in joint-space narrowing and bone erosion scores of patients treated with REMICADE plus methotrexate compared to placebo patients treated with methotrexate alone.
The ATTRACT Trial: One of the Largest of Its Kind
The two-year ATTRACT trial is among the largest and longest controlled clinical trials involving patients with rheumatoid arthritis. The study compared REMICADE in combination with methotrexate, to placebo with methotrexate, in 428 patients. Methotrexate is a standard treatment for rheumatoid arthritis.
The 54-week data presented today demonstrated an overall median change from baseline for radiographic scores of 0.0 among patients treated with the combination of REMICADE plus methotrexate (n=285) compared to a median change of 4.0 for patients treated with methotrexate alone (n=63). This result was maintained through two years. The methotrexate-only findings (control arm) represent a 7-to-8 percent deterioration in radiographic scores. This is comparable to that previously reported for patients with established rheumatoid arthritis treated with disease-modifying anti-rheumatic drug therapy, including methotrexate.
The ATTRACT trial was a double-blind, placebo-controlled, randomized clinical study conducted at 34 centers in North America and Europe. It evaluated prevention of structural damage using the van der Heijde modified Sharp score, which assesses a combination of bone erosion and joint-space narrowing.
The results from ATTRACT indicate that REMICADE was generally well tolerated. The most common adverse events included upper respiratory infections, headache, 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 intravenous infusion reactions was also low in REMICADE plus methotrexate patients (five percent) compared to those receiving methotrexate alone (two percent).
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 for treatment of signs and symptom of rheumatoid arthritis and additional information regarding warnings, precautions and adverse events.
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. Its 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 (NYSE: JNJ), the worldwide manufacturer of healthcare products. For additional information about Centocor and its products, visit Centocor's websites: http://www.centocor.com or http://www.remicade.com.