Centocor, Inc. Release: Patients With Active Psoriatic Arthritis Receiving REMICADE(R) Therapy Achieve 'Major Clinical Response' In Arthritic Component Of Disease

SAN DIEGO, Nov. 16 /PRNewswire/ -- New data, including two-year treatment duration, show a significantly higher proportion of patients with active psoriatic arthritis receiving REMICADE(R) (infliximab) achieved and sustained a high degree of clinical improvement in arthritis, as assessed using the rheumatoid arthritis (RA) definition for "major clinical response," compared with patients receiving placebo. "Major clinical response" is defined as maintenance of a 70 percent improvement in the American College of Rheumatology score (ACR 70) for six continuous months. REMICADE maintenance therapy also resulted in the inhibition of structural damage and significant improvements in functional status and quality of life as maintained over the course of one year. Investigators will present these long-term Phase 2 and 3 study findings this week at the American College of Rheumatology 2005 Annual Scientific Meeting. REMICADE is currently indicated for reducing signs and symptoms of active arthritis in patients with psoriatic arthritis.

"Previous study findings have shown the rapidity and therapeutic intensity of infliximab in treating the joint and skin manifestations associated with active psoriatic arthritis," said Arthur Kavanaugh, MD, Director, Center for Innovative Therapy, Division of Rheumatology, Allergy and Immunology, University of California, San Diego, and lead study investigator. "These data demonstrate the rapid efficacy of infliximab can be sustained over time, especially as it relates to the arthritic component of this complex disease."

An analysis of two double-blind, placebo-controlled trials, Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT) and Induction and Maintenance Psoriatic Arthritis Clinical Trial 2 (IMPACT 2), followed patients for two years (98 weeks) and one year (54 weeks), respectively, and confirmed a significant, high degree of clinical responses in the arthritic component of the disease. Placebo patients in both studies crossed over to active treatment by week 16 in IMPACT and week 24 in IMPACT 2. In IMPACT, 35 percent of all randomized patients (including patients originally randomized to REMICADE and placebo) entering the second year (27 out of 78) achieved an ACR 70 improvement at week 98. In IMPACT 2, 20 percent of REMICADE randomized patients (20 out of 100) achieved this high degree of improvement at week 54.

In both IMPACT and IMPACT 2, "major clinical response," a post hoc analysis, was defined for REMICADE randomized patients as maintenance of a 70 percent improvement in ACR 70 for six continuous months anytime during the study. Placebo patients were conservatively counted as achieving "major clinical response" if they had achieved ACR 70 improvement at the last visit before receiving REMICADE. In IMPACT, 31 percent of patients randomized to REMICADE (16 out of 52) achieved a "major clinical response" versus zero percent of patients receiving placebo (P < 0.001).

In IMPACT 2, 12 percent of REMICADE randomized patients (12 out of 99) achieved a "major clinical response" versus two percent of patients receiving placebo (P = 0.006). "Major clinical response" identifies a high degree of sustained clinical improvement in arthritis but does not currently account for the skin disease associated with psoriatic arthritis.

REMICADE Inhibits Progression Of Radiographic Damage In Patients With Active Psoriatic Arthritis: 1-Year Results From IMPACT 2

According to one-year results from the IMPACT 2 trial, radiographic analyses showed treatment with REMICADE resulted in significantly less progression of structural damage, compared with patients receiving placebo, as measured by the change in baseline in van der Heijde-Sharp (vdH-S) score in which higher scores indicate greater structural damage, while lower scores indicate less structural damage. At as early as 24 weeks of treatment, REMICADE patients experienced a mean change (+/- standard deviation) in vdH-S score of -0.70 (+/- 2.53) from baseline, compared with an average change of 0.82 (+/- 2.62) in the placebo group (P < 0.001). At week 54, patients who received a full 54-week regimen of REMICADE experienced a mean change of -0.94 (+/- 3.40) from baseline, compared with an average change of 0.53 (+/- 2.60) in patients who crossed over from placebo to REMICADE (P = 0.001). REMICADE and crossover patients experienced a total improvement of -0.24 (+/- 2.45) and -0.29 (1.98), respectively, from week 24 to 54.

"These radiographic findings are significant in the treatment of active psoriatic arthritis, which like rheumatoid arthritis, is a progressive immune- mediated inflammatory disease," said Desiree van der Heijde, MD, PhD, Professor of Rheumatology, University of Maastricht in the Netherlands and lead study investigator. "The inhibition of joint destruction is critical in the management of disease and these radiographic data show the long-term, sustained effect of REMICADE therapy in the course of the disease."

REMICADE Therapy Results In Sustained Improvement In Functional Status And Quality Of Life In Patients With Psoriatic Arthritis: 1-Year Results From The IMPACT 2 Study

One-year data presented from IMPACT 2 showed REMICADE-treated patients experienced sustained improvement in health-related quality of life, as assessed by the Short Form 36 (SF-36), a questionnaire that assesses impact in the areas of physical function, pain, social function and general health perceptions, in which higher scores indicate better well-being. At week 14, REMICADE patients showed significant improvement in the physical component summary (PCS) and the mental component summary (MCS) of the SF-36 compared with patients receiving placebo. Additionally, REMICADE-treated patients showed a median increase of 8.7 in PCS score, compared with a 1.0 increase in placebo-treated patients (P < 0.001). Patients receiving REMICADE also experienced a median improvement of 2.1 in MCS score, compared with 0.5 in placebo-treated patients (P < 0.001). At week 54, median improvement from baseline in PCS and MCS in the REMICADE group was 7.4 and 2.8, respectively, and the median improvement in the placebo/REMICADE group, the group of patients initially receiving placebo and crossed over to REMICADE by week 24, was 10.2 and 1.9, respectively. At week 14, the median improvement from baseline in Health Assessment Questionnaire (HAQ) was 43 percent in the REMICADE group, compared with no change in the placebo group (P < 0.001). This improvement was maintained at week 54, with a 50 percent median improvement from baseline in the group randomized to REMICADE, indicating significantly improved physical function.

About Psoriatic Arthritis

Psoriatic arthritis involves joint pain and swelling that can lead to debilitation coupled with inflamed, scaly, red patches of psoriasis. Symptoms may include stiffness and tenderness of the joints and surrounding tissue, reduced range of motion, nail changes and redness and pain of the eye, uveitis. Joints of the hands, wrists, knees, ankles, feet, lower back and neck are commonly affected. Approximately one million Americans have psoriatic arthritis, and the disease affects both men and women equally, most commonly between the ages 30 and 50.

About IMPACT

IMPACT was a Phase 2b randomized, double-blind, placebo-controlled study that involved 104 patients with active psoriatic arthritis (defined as affecting at least five joints) who failed at least one disease-modifying anti-rheumatic drug (DMARD) and was conducted at nine study centers in the U.S., Canada and Europe. The trial was designed to study the efficacy and safety of REMICADE compared with placebo in patients with active psoriatic arthritis. Patients received either REMICADE (5 mg/kg) or placebo administered at weeks 0, 2, 6 and 14. The REMICADE group continued on maintenance treatments every eight weeks. Beginning at week 16, patients randomized to the placebo group received an induction regimen of REMICADE followed by maintenance treatment every eight weeks. A total of 78 patients entered the second year open-label extension of the trial.

REMICADE was generally well tolerated in this study, with similar proportions of patients experiencing adverse events (AEs) in both REMICADE and placebo groups. No deaths, cases of tuberculosis or other opportunistic infections were reported and serious infections were uncommon. There were no serious infusion reactions. Common side effects in the placebo-controlled period were similar in both the groups and included upper respiratory tract infection, headache, bronchitis and influenza-like symptoms. Through year one, the most common AEs included upper respiratory tract infection, nonproductive cough, headache and influenza-like symptoms. The incidence and type of AEs observed in year two were similar to those observed during the first year of treatment. Two patients had serious AEs relating to neoplasms, one a benign mucinous abdominal cystoma and a second ductal adenocarcinoma of the pancreas three months after week 98, both considered unrelated to study medication.

About IMPACT 2

IMPACT 2 was a Phase 3 randomized, double-blind, placebo-controlled study of 200 patients with active psoriatic arthritis (defined as affecting at least five joints). The study evaluated the safety and efficacy of REMICADE in patients who had an inadequate response to DMARDs or nonsteroidal anti-inflammatory drugs (NSAIDs). Patients received REMICADE 5mg/kg or placebo at weeks 0, 2, 6 and every 8 weeks until week 22. At week 16, placebo patients who had < 10% improvement from baseline in both swollen and tender joint counts entered early escape and received REMICADE.

At week 24, the remaining placebo patients crossed over to REMICADE, and REMICADE patients continued on 5 mg/kg every eight weeks through week 46.

Through 24 weeks, a similar proportion of patients experienced AEs in each treatment group. No deaths, cases of tuberculosis or other opportunistic infections or serious infusion reactions were reported and serious infections were uncommon. There were more patients with serious AEs through week 24 in the combined (those originally randomized to REMICADE and placebo patients who entered early escape) REMICADE group (8.7 percent) than in the placebo group (6.2 percent). Laboratory abnormalities were uncommon, with an elevation in liver function tests being the most common abnormality. During the placebo- controlled period, markedly abnormal alanine aminotransferase (ALT) values (predefined as greater than 150 IU/L and greater than or equal to 100 percent increase from baseline) occurred in 5 (3 percent) of the subjects in the combined REMICADE group compared with no subjects in the placebo group. Within 24 weeks of treatment one placebo-treated patient was diagnosed with basal cell carcinoma. During the continued treatment with REMICADE beyond week 24, one REMICADE patient was diagnosed with Hodgkin's lymphoma. See "Important Safety Information" below.

About REMICADE

REMICADE is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies and has demonstrated broad clinical utility in rheumatoid arthritis (RA), Crohn's disease (CD), psoriatic arthritis (PsA), ulcerative colitis (UC), and ankylosing spondylitis (AS). The safety and efficacy of REMICADE have been well established in clinical trials over the past 12 years and through commercial experience with over 600,000 patients treated worldwide.

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 RA. REMICADE is the only biologic indicated for the treatment of patients with moderately-to-severely active CD 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 CD. In December 2004, REMICADE was approved for reducing signs and symptoms in patients with active AS. On May 13, 2005, REMICADE was approved for reducing signs and symptoms of active arthritis in patients with PsA. Additionally, on September 15, 2005, REMICADE was approved for reducing signs and symptoms, achieving clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active UC who have had an inadequate response to conventional therapy. This approval makes REMICADE the first and only biologic approved for the treatment of moderate to severe UC.

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 (3 mg/kg), CD (5 mg/kg), PsA (5 mg/kg), and UC (5 mg/kg), REMICADE is a two-hour infusion administered every 8 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 AS (5 mg/kg), REMICADE is a two-hour infusion administered every 6 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6.

Important Safety 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), sepsis and pneumonia. 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.

There have been rare cases of serious liver injury in people taking REMICADE, some fatal. Contact your doctor immediately if you develop symptoms such as jaundice (yellow skin and eyes), dark brown urine, right-sided abdominal pain, fever, or severe fatigue.

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 a type of blood cancer called lymphoma in patients on REMICADE or other TNF blockers are rare but occur more often than expected for people in general. People who have been treated for rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, or psoriatic arthritis for a long time, particularly those with highly active disease may be more prone to develop lymphoma. Cancers, other than lymphoma, have also been reported. If you take REMICADE or other TNF blockers, your risk for developing lymphoma or other cancers may increase. You should also tell your doctor if you have had or develop lymphoma or other cancers while you are 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 US prescribing information, at http://www.remicade.com.

About Centocor

Centocor is harnessing the power of world-leading research and biomanufacturing to deliver innovative biomedicines that transform patients' lives. Centocor has already brought innovation to the treatment of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and ulcerative colitis.

The world leader in monoclonal antibody production and technology, Centocor has brought critical biologic therapies to patients suffering from debilitating immune disorders. Centocor, Inc. is a wholly owned subsidiary of Johnson & Johnson, a worldwide manufacturer of healthcare products.

Centocor, Inc.

CONTACT: Michael Parks of Centocor, Inc., +1-215-325-4010, or Mobile:+1-215-983-8000

Web site: http://www.remicade.com/