Long-Term Remicade Data Demonstrate Sustained Efficacy in Treatment of Active Psoriatic Arthritis

Drug News-- June 10, 2005

Long-Term Remicade Data Demonstrate Sustained Efficacy in Treatment of Active Psoriatic Arthritis

New Data Also Show Significant Improvement in Health-Related Quality-of-Life Measures in Patients with Psoriatic Arthritis

VIENNA, AUSTRIA, June 10, 2005 -- Two-year data presented today at the European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology show Remicade (infliximab) provides sustained improvement in the signs and symptoms of arthritis, psoriasis, dactylitis and enthesopathy in patients with active psoriatic arthritis. Additionally, data showing significant improvements in physical and mental quality-of-life measures in patients treated with Remicade were presented. First approved in 1998, Remicade has been used to treat over a half a million patients worldwide and is indicated for the treatment of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Remicade is the only tumor necrosis factor-alpha (TNF-a) blocker approved to treat all four of these serious Immune-Mediated Inflammatory Disorders.

Findings from a 2-year, open-label extension of the Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT) showed that nearly 62 percent of Remicade-treated patients (n=78) sustained at least 20 percent improvement in arthritis symptoms, according to the American College of Rheumatology scoring criteria (ACR 20). Patients receiving Remicade therapy also showed sustained improvement during year 2 in psoriasis symptoms. After 98 weeks of treatment, 64 percent of patients with a baseline Psoriasis Areas Severity Index (PASI) of at least 2.5 (n=25) achieved a PASI 75 response, representing significant and sustained improvement in skin disease. Moreover, patients maintained response in measures of dactylitis (swelling of the digits in the hands or feet) and enthesopathy (inflammation of a tendon or ligament insertion to the bone), two common disease manifestations estimated to affect more than one third of patients with psoriatic arthritis.

"These data illustrate that response to Remicade is well maintained for up to two years in patients with psoriatic arthritis," said Arthur Kavanaugh, MD, Director, Center for Innovative Therapy, Division of Rheumatology, Allergy, and Immunology, University of California at San Diego. "Not only do patients rapidly experience improvements in joint and skin symptoms, but they experience improvements in dactylitis and enthesopathy."

Additional data were presented from the Infliximab Multinational Psoriatic Arthritis Clinical Trial 2 (IMPACT 2) showing the effect of Remicade on health-related quality-of-life (HRQL) in psoriatic arthritis patients. The impact of improvements in skin and joint components of the disease on HRQL were evaluated in a post-hoc analysis involving 200 patients randomized to receive infusions of Remicade (5 mg/kg) or placebo at weeks 0, 2, 6, 14 and 22. "Inflammatory diseases such as psoriatic arthritis can severely impact patients' abilities to function and lead normal, everyday lives," said Arthur Kavanaugh, MD. "These results demonstrate that treatment with infliximab provides a significant clinical benefit, which may lead to a positive effect on patients' physical and emotional well-being."

Study results revealed that Remicade patients achieving both ACR 20 (58 percent vs. 11 percent of patients receiving placebo, P < 0.001) and PASI 75 (64 percent vs. 2 percent of patients receiving placebo, P < 0.001) demonstrated the greatest improvement in HRQL, as measured by Physical Component Summary (PCS) and Mental Component Summary (MCS) according to the Short-form (SF-36) scoring system, and the Health Assessment Questionnaire Disability Index (HAQ). Baseline mean PCS (32) and MCS (46.2) scores were similar between treatment groups and were below the general U.S. population, indicating substantially impaired HRQL. At week 14, mean improvements in PCS [9.1 vs. 1.1, P < 0.001], MCS [3.8 vs. -1.2, P = 0.001] and eight scales of SF-36 (P < 0.01) and mean percent improvement in HAQ [48.6 percent vs. -18.4 percent, P < 0.001] were significantly greater for patients receiving Remicade therapy versus the placebo group.

In May 2005, Remicade was approved in the U.S. for reducing signs and symptoms of active arthritis in patients with psoriatic arthritis. In September 2004, Remicade received European Union approval, 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.

About Impact

IMPACT was a randomized, double-blind, placebo-controlled study that involved 104 patients with active psoriatic arthritis (defined as affecting at least five joints) who were enrolled at nine 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 8 weeks. Beginning at week 16, patients randomized to the placebo group received an induction regimen of Remicade followed by maintenance treatment every 8 weeks.

In year 2, patients received infusions of Remicade every 8 weeks from week 54 to week 94, with final study assessments at week 98. The primary efficacy outcome was an improvement of at least 20 percent from baseline according to the American College of Rheumatology (ACR) criteria at week 98. The proportions of patients achieving ACR 50 and ACR 70 response were also determined. Additional predefined clinical efficacy assessments included PASI, the Disease Activity Score (DAS 28), the Health Assessment Questionnaire (HAQ), ratings of enthesopathy and dactylitis and the Psoriatic Arthritis Response Criteria (PsARC).

Remicade was generally well tolerated in this study, with similar proportions of patients experiencing adverse events (AEs) in each group. No deaths, 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 a similar number of patients with serious AEs in the Remicade and placebo treatment groups. Through year 1, 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 2 were similar to those observed during first year of treatment. Two patients had serious AEs relating to neoplasms, a benign mucinous abdominal cystoma and a ductal adenocarcinoma of the pancreas 3 months after week 98, both considered unrelated to study medication. See "Important Safety Information" below.

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 disease-modifying anti-rheumatic drugs (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. In patients with > 3 percent body surface area (BSA) psoriasis involvement at baseline, psoriasis activity was assessed using PASI at baseline and weeks 2, 6, 14 and 24.

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. 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 lymphoma. Laboratory abnormalities were uncommon, with an elevation in liver function tests being the most common abnormality. There were more patients with serious AEs in the Remicade group (8.7 percent) than in the placebo group (6.2 percent). See "Important Safety Information" below.

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. 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 of 30 and 50. According to the Arthritis Research Campaign, approximately 1 in 50 people have psoriasis in the United Kingdom and about 1 in 14 of these individuals will develop psoriatic arthritis.

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 rheumatoid arthritis (RA) and Crohn's disease (CD) in North America, the European Union (EU) and Japan. In the EU and in the U.S., Remicade is approved for the treatment of active ankylosing spondylitis (AS) and psoriatic arthritis.

In the EU, Remicade is indicated for the treatment of severe, active CD in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. Remicade also is indicated for the treatment of fistulizing, active CD in patients who have not responded despite a full and adequate course of therapy with conventional treatment (including antibiotics, drainage and immunosuppressive therapy).

For RA patients in the EU, Remicade, in combination with methotrexate, is indicated for the reduction of signs and symptoms as well as the improvement in physical function in patients with active disease when the response to disease-modifying drugs, including methotrexate, has been inadequate, and in patients with severe, active and progressive disease not previously treated with methotrexate or other DMARDs. In these patient populations, a reduction in the rate of the progression of joint damage, as measured by X-ray, has been demonstrated. In the EU, Remicade is also indicated for treatment of AS in patients who have severe axial symptoms, elevated serological markers of inflammatory activity and who have responded inadequately to conventional therapy.

In addition, Remicade, in combination with methotrexate, is approved for the treatment of active and progressive psoriatic arthritis in patients who have responded inadequately to disease-modifying anti-rheumatic drugs.

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 the treatment of active AS and in May 2005, Remicade was approved for reducing signs and symptoms of active arthritis in patients with psoriatic arthritis in the U.S.

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, CD, and psoriatic arthritis, 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. In AS, Remicade is a two-hour infusion (5 mg/kg) administered every six weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6. The safety and efficacy of Remicade have been well established in clinical trials over the past 12 years and through commercial experience with over a half a million patients treated worldwide.

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 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 important information about Remicade, including full U.S. prescribing information, on the Remicade website.

Source: Centocor

Posted: June 2005


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