FDA Approves REMICADE® Regimen for Moderate to Severe Rheumatoid Arthritis

Main Category: Arthritis / Rheumatology
Article Date: 01 Oct 2004 - 9:00 PDT


New Indication Based on First Study to Show Superiority of Anti-TNF Regimen Over Current Standard of Treatment in Signs and Symptoms, Radiographic Progression and Physical Function in Patients with Early RA.

Centocor, Inc., announced today that the U.S. Food and Drug Administration (FDA) has approved an expanded label for REMICADE® (infliximab) in combination with methotrexate (REMICADE® regimen), as a first line regimen to treat patients with moderate to severe rheumatoid arthritis (RA). The expanded label eliminates the requirement that patients must fail to respond to methotrexate, the current standard of treatment for RA, before starting on the REMICADE® regimen. These patients can now benefit from treatment with the REMICADE® regimen, which has been shown to reduce signs and symptoms, inhibit further joint destruction and improve physical function.

Intervention early is critical to change the course of joint destruction in this debilitating disease. In the ASPIRE (Active Controlled Study of Patients Receiving Infliximab for Treatment of Rheumatoid Arthritis of Early Onset) study, more than 80 percent of patients had evidence of erosive joint damage despite the fact that the median disease duration was only seven months. This study demonstrated that the REMICADE® regimen was superior to methotrexate alone in changing the course of the disease when given early. The majority of patients treated with the REMICADE® regimen experienced no progression of structural damage while the majority of patients treated with methotrexate alone progressed significantly despite titration to high doses of methotrexate.

"The ASPIRE trial demonstrated that with early, intensive intervention patients can achieve substantial symptomatic improvement," said David E. Yocum, M.D., director, Arizona Arthritis Center, the University of Arizona College of Medicine, and ASPIRE investigator. "Moreover, in a subset of patients without joint damage at baseline, REMICADE® plus methotrexate provided greater benefit than methotrexate alone in maintaining an erosion free state. To date, no other anti-TNF combination regimen has been shown to be more effective than methotrexate alone in stopping joint damage in patients with early disease."

"The ASPIRE data confirm that treating patients early in their disease with REMICADE® can change the course of structural damage associated with RA," said Jerome A. Boscia, M.D., senior vice president, Clinical Research and Development, Centocor, Inc. "The magnitude of benefit seen with the REMICADE® regimen and its effect on joint progression was a key factor in the approval of this new indication. The approval further confirms the positive benefit-to-risk profile of REMICADE®."

About ASPIRE

The FDA approval is based on the results of ASPIRE, the largest controlled trial ever conducted exclusively in RA patients with early disease, (< three years duration), which found REMICADE® plus methotrexate to be superior to methotrexate alone in patients with moderately to severely active disease. ASPIRE was a 54-week, randomized, double blind, active control study involving 1,004 patients with early disease enrolled in 125 centers in North America and Europe. At randomization, all patients received methotrexate and either placebo, 3 mg/kg of REMICADE® or 6 mg/kg of REMICADE® at weeks zero, two and six and then every eight weeks thereafter. The ASPIRE trial demonstrated superiority of the REMICADE® regimen over methotrexate alone on all three primary endpoints, including reduction of signs and symptoms, inhibition of the progression of structural damage and improvement in physical function.

The most commonly reported adverse events were upper respiratory infection, nausea and headache. Serious infections included pneumonia, TB and sepsis. Please read important information about REMICADE®, including full prescribing information, at www.remicade.com. See "Important Information" below.

About Rheumatoid Arthritis

RA is a chronic, progressive disease, and research suggests that a critical therapeutic window may exist within the first two years of disease onset when the rate of radiographic progression of the disease can be "reset."1,2,3 Radiographic changes occur within two years of disease onset in 50-70 percent of RA patients.4 The American College of Rheumatology (ACR) suggests control of disease progression should start early to limit joint damage in RA.3 RA is associated with substantial disability and economic losses, and one study showed that one-third of patients in the UK who were employed became work-disabled within two years of disease onset.5 Rheumatologic disorders also account for 25 percent of Social Security disability payments.6

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 live in a region where histoplasmosis or coccidioimycosis 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 had a disease that affects the nervous system, or if you experience any numbness, weakness, tingling or visual disturbances while taking REMICADE®.

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 http://www.remicade.com.)

About REMICADE®

REMICADE® is a monoclonal antibody that specifically targets and irreversibly 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 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. Additionally, REMICADE® has received a positive opinion in the EU from the Committee for Medicinal Products for Human Use (CHMP) recommending approval of expanded labeling for REMICADE®, in combination with methotrexate, for the treatment of active and progressive psoriatic arthritis in patients who have responded inadequately to disease modifying anti-rheumatic drugs (DMARDs).

In most countries, REMICADE®, in combination with methotrexate, is indicated for the treatment of patients with moderately-to-severely active rheumatoid arthritis who have had an inadequate response to methotrexate. 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 patients, REMICADE® is a two-hour infusion administered every eight weeks, following a standard induction regimen that requires treatment at weeks zero, two and six. As a result, REMICADE® patients may require as few as six treatments each year. The safety and efficacy of REMICADE® have been well established in clinical trials conducted over the past 12 years and through commercial experience with more than 500,000 patients treated worldwide.7

About Centocor, Inc.

Centocor, Inc., is a leading biopharmaceutical company that creates, acquires and markets cost-effective therapies that yield long-term benefits for patients and the health care community. The company is dedicated to the research and development of treatments for a wide range of Immune-Mediated Inflammatory Disorders (I.M.I.D.), such as arthritis and inflammatory skin diseases and for cancer. 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, Inc., is a wholly owned subsidiary of Johnson & Johnson, the worldwide manufacturer of health care products.

Centocor, Inc., has exclusive marketing rights to REMICADE® in the United States. 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 Tanabe Seiyaku, Ltd., will market the product.

References

1 Landewe RB, Boers M, Verhoeven AC, et al. COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum. 2002;46:347-356.

2 Egsmose C, Lund B, Borg G, et al. Patients with rheumatoid arthritis benefit from early second line therapy: five year follow up of a prospective double blind placebo controlled study. J. Rheumatol. 1995;22:2208-2213.

3 American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines, 2002 Update.

4 van der Heijde DM. Joint erosions and patients with early rheumatoid arthritis. Br J Rheumatol. 1995;34(suppl 2):74-78.

5 Barrett EM, Scott DGI, Wiles NJ, Symmons DPM. The impact of rheumatoid arthritis on employment status in the early years of disease: a UK community-based study. Rheumatology. 2000;39:1403-1409.

6 Social Security Disability Insurance Program.

7 Data on file at Centocor, Inc.

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