REMICADE Study Demonstrates Significant and Rapid Improvements in the Course of Psoriatic Arthritis; Data Show Promise for Clinical and Structural Damage Improvements in Psoriatic Arthritis.

SAN ANTONIO -- Treatment with REMICADE(R) may provide significant and rapid improvements in both the arthritis and psoriasis of patients with active psoriatic arthritis (PsA), according to data from two trials presented this week at the American College of Rheumatology (ACR) 68th Annual Scientific Meeting.

In the IMPACT 2 study, a phase III trial, REMICADE provided a 70 percent improvement or greater (as measured by ACR 70) in symptoms of arthritis in 27 percent of patients, compared with only 2 percent of patients on placebo at 24 weeks. Treatment with REMICADE also resulted in a dramatic 90 percent or greater improvement in PASI score for nearly 40 percent of patients and 100 percent improvement in PASI score for 21 percent of patients as compared to none of the placebo patients. Improvement in arthritis and psoriasis was seen as early as week 2 and maintained throughout the study. In addition, REMICADE was efficacious in the treatment of dactylitis and enthesopathies, two common manifestations of PsA causing pain and swelling. REMICADE is currently approved for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD).

"With results of this magnitude in both the joint and skin components of the disease, we are beginning to set higher expectations of what can be achieved in treating patients with psoriatic arthritis," said one of the study's lead investigators, Gerald G. Krueger, M.D., Department of Dermatology, University of Utah Health Sciences Center. "A 100 percent improvement in PASI represents complete clearance of the skin disease associated with psoriatic arthritis."

Additionally, an analysis of X-rays from the IMPACT (Infliximab Multinational Psoriatic Arthritis Controlled Trial) trial revealed for the first time, radiographic evidence of the positive effects of REMICADE on inhibiting the structural disease progression of PsA. The study results suggest the annual progression rate, as measured by X-ray of hand and feet, was reduced by REMICADE treatment from a predicted rate of a mean 5.8 modified van der Heijde-Sharp score points per year prior to REMICADE treatment to -1.8 score points per year during REMICADE administration. When using the van der Heijde-Sharp scoring method, a lower number represents less bone erosion, therefore, according to this data there was less apparent joint damage at the end of the trial than at the beginning.

"Patients receiving infliximab in this study exhibited marked improvements in the progression of joint deterioration," said one of the study's lead investigators, Arthur Kavanaugh, M.D., Professor of Medicine, University of California at San Diego's Division of Rheumatology, Allergy and Immunology, and Director of the UCSD Center for Innovative Therapy. "This is one of the first studies to definitively show that treatment with infliximab can essentially stop the structural progression of the disease and, while more study is needed, it may suggest that it could be possible to reverse existing damage."

REMICADE is a monoclonal antibody that specifically targets and 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 RA and CD and in a wide range of Immune-Mediated Inflammatory Disorders (I.M.I.D.) in which REMICADE is currently being studied.

About IMPACT 2: Significant Improvements in Joint and Skin Involvement in PsA

IMPACT 2 is a Phase III, multi-center, randomized, double-blind, placebo-controlled trial initiated to evaluate the safety and efficacy of REMICADE in patients with active PsA who had an inadequate response to disease-modifying antirheumatic drug (DMARD) therapy or to nonsteroidal anti-inflammatory drug (NSAID) therapy. IMPACT 2 reinforces the findings of an earlier study, IMPACT, which showed that REMICADE significantly improved the signs and symptoms of PsA, including psoriasis in 104 patients who failed treatment with at least one DMARD.

IMPACT 2 demonstrated that treatment with REMICADE 5 mg/kg resulted in marked improvements in patients with PsA and significant improvement in both joint and skin disease was evident as early as week 2. In a poster presented this week, researchers showed that at week 14, more than half of the patients in the REMICADE treatment group achieved significant improvements in the signs and symptoms of PsA as measured by the proportion of patients achieving ACR 20 (58 percent of the REMICADE patient group versus 11 percent placebo, p less than 0.001) and 75 percent or greater improvement in the Psoriasis Area and Severity Index, otherwise referred to as PASI (63.9 percent of the REMICADE treatment group versus 2.3 percent placebo, p less than 0.001). The response was achieved regardless of methotrexate use or level of joint involvement at baseline.

Furthermore, a significant portion of subjects in the REMICADE treatment group achieved ACR 70 and PASI 90 as early as week 6 and maintained these promising results throughout the study. At week 24, results show that 27 percent of patients treated with REMICADE exhibited a 70 percent or greater improvement in symptoms of arthritis (as measured by ACR 70) compared with 2 percent in the placebo group (p less than 0.001) and 39 percent of patients showed a 90 percent or greater improvement in psoriasis (as measured by PASI 90) compared with none in the placebo group (p less than 0.001).

REMICADE was generally well tolerated in this study, with similar numbers of patients experiencing adverse events in each group. No deaths or cases of tuberculosis or other opportunistic infections were reported, and serious infections were uncommon. There was a case of basal cell carcinoma of the skin in one placebo patient. Significant laboratory abnormalities were unusual, with the elevation in transaminases being the most common abnormality. See Important Information below.

About IMPACT: Influence of Treatment on X-Ray Disease Progression

IMPACT was a randomized, double-blind, placebo-controlled study that involved 104 patients with active PsA (defined as affecting at least five joints) who were enrolled at nine centers in the United States, Canada and Europe. The trial was designed to study the efficacy and safety of REMICADE compared with placebo in patients with active PsA. Patients received either REMICADE (5 mg/kg) or placebo administered at weeks 0, 2, 6 and 14. Beginning at week 16, patients randomized to the placebo group received an induction regimen of REMICADE followed by maintenance treatment.

Patients given REMICADE experienced significant improvement in their arthritis, as measured by the ACR 20, 50 and 70 response criteria, used to assess disease activity improvement. Significant psoriasis improvement was also seen among 38 patients with active skin disease. Researchers analyzed the progression of structural damage over the course of one year in patients with active PsA participating in IMPACT. Analysis of 70 patients with X-rays evaluable at baseline and week 50 demonstrated treatment with REMICADE reduces the progression of structural damage associated with PsA. Bone erosion, joint space narrowing and total radiographic scores were determined using a van der Heijde-Sharp scoring method modified for PsA. The annual progression rate was reduced by REMICADE treatment from a predicted rate of mean 5.8 modified van der Heijde-Sharp score points per year prior to REMICADE treatment, to -1.8 score points per year during REMICADE administration. Furthermore, in both groups, nearly 85 percent of patients had no progression in structural damage, defined as a worsening from baseline in total modified van der Heijde-Sharp score of less than or equal to 0.5.

Remicade was generally well tolerated in this study, with similar numbers of patients experiencing adverse events in each group. No deaths, malignancies, cases of tuberculosis or other opportunistic infections were reported and serious infections and infusion reactions were uncommon. Most common side effects in the placebo-controlled period were similar in both the placebo and REMICADE groups and included upper respiratory tract infection, headache, bronchitis and influenza-like symptoms. Overall, there was similar number of patients with serious adverse events in the REMICADE and placebo treatment groups. See Important Information below.

About PsA

PsA effects men and women equally and can develop at any age, although it most commonly appears between the ages of 30 and 50. In most instances, psoriasis signs and symptoms, such as scaly rashes, occur as long as 10 years before the patient begins to suffer from arthritis. Symptoms of PsA include stiffness, pain, swelling and tenderness of the joints and the soft tissue around them; reduced range of motion; and tiredness; nail changes; and redness and pain of the eye. Joints commonly affected by PsA are the hands, wrists, knees, ankles, lower back and neck.

About REMICADE

REMICADE is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) 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.

In September, the European Commission gave approval for 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.

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 0, 2 and 6. 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 over the past 12 years and through commercial experience with more than a half million patients treated worldwide.

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 accompanying patient information sheet)

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.

Abstract: Infliximab Significantly Improves Joint and Skin Involvement
in Psoriatic Arthritis to a Substantial Extent and Irrespective of
Baseline Joint Involvement or MTX Use: Analysis of a Clinical Response
from the IMPACT 2 Trial

Author:  Kavanaugh, et al.

Date:  Wednesday, October 20, 2004

Time:  8:00 a.m. to 4:00 p.m.

Location:  Exhibit Hall C - D



Abstract: The Infliximab Multinational Psoriatic Arthritis Controlled
Trial (IMPACT): Results of Radiographic Analyses after 1 year

Author: Antoni, et al.

Date: Tuesday, October 19, 2004

Time: 3:15 p.m. to 4:00 p.m.

Location: Room 214 C - D