WASHINGTON, DC, May 23, 2007— Findings presented today at Digestive Disease Week® 2007 (DDW), from long-term extensions of the ACT trials (Active Ulcerative Colitis 1 & 2) show that subjects with moderately to severely active ulcerative colitis (UC) who had responded to REMICADE® (infliximab) in the blinded phase of the trials maintained improvement in their clinical symptoms for up to two years.
The ACT extension trials were conducted in both the United States and Europe, under co-principle investigators William Sandborn, M.D. of the Mayo Clinic and Walter Reinisch, M.D., of the University Hospital Vienna, Austria. The data show that for patients who completed follow-up through week 56 of the extension trials, 92 percent reported mild or no disease activity, as measured by the Physician's Global Assessment (PGA). For patients followed through week 104, 97 percent reported mild or no disease activity.
At week 0 of the ACT extension trials, 76 percent of 229 responder patients enrolled had mild or no disease activity, as indicated by a PGA score of 0 or 1, and 41 percent had no disease activity (PGA score of 0). At week 56, 92 percent of those patients remaining in the extension trials (n=181) had mild or no disease activity, and 61 percent had no disease activity. At week 104, 97 percent of those patients remaining in the extension trials (n=97) had mild or no disease activity, and 75 percent had no disease activity.
"The data demonstrate the sustained efficacy of REMICADE for many patients with UC," said co-principle investigator Walter Reinisch, M.D., of the University Hospital Vienna, Austria. "Because UC is a chronic condition, many patients live with cycles of recurring flares. This can greatly hinder a person's social and professional life. The availability of therapies that quickly reduce symptoms and maintain response and remission long term is a significant benefit to patients."
Separate data also presented at DDW today show the significant impact of UC on patients' productivity, employment and social activities. A survey of 1,000 patients who rated their UC symptoms on a scale of 1 to 5, with 5 being very severe, showed that patients with more severe disease reported greater disability, significantly more days missed from work and significantly more days of reduced productivity, compared with patients with less severe disease (P < 0.01). In fact, 19 percent of patients with the most severe disease were on long- or short-term medical leave from work, compared with less than seven percent of patients whose disease was less severe (P < 0.01). Of patients who were employed, those with the most severe disease missed an average of 19 days of work in the past year, compared with one day for those with the mildest disease (P < 0.01). Furthermore, even when at work, patients who rated their disease as more severe reported being less productive on more than 30 days in the past year, underscoring the negative impact of UC on patients' ability to function in the workplace.
"Many patients with ulcerative colitis report experiencing extremely bothersome symptoms, that affect many areas of their lives, including their ability to maintain full-time employment and make and keep social engagements," said Richard J. Geswell, President, Crohn's & Colitis Foundation of America. "Since patients with more severe symptoms experience more difficulties than those with milder disease, a treatment that rapidly reduces UC symptoms and keeps disease activity at bay over time may reduce the impact of the disease on patients' work status and productivity."
About the ACT Long-Term Extension Patients with moderate to severe UC, defined as a baseline Mayo score ≥ 6 and ≤ 12, who were unresponsive to or intolerant to at least one standard therapy, including corticosteroids, immunosuppressants or 5ASAs, were enrolled in ACT 1 (n=364) or ACT 2 (n=364). The 728 patients were randomized to receive REMICADE 5 mg/kg, REMICADE 10 mg/kg or placebo at weeks 0, 2, 6 and every subsequent 8 weeks through week 22 (ACT 2) or week 46 (ACT 1). Patients were allowed to continue to receive conventional therapy.
Patients who had benefited from treatment with REMICADE and, in the investigators opinion, could enroll in the extension trials; 118 patients entered the ACT 1 extension and 111 patients entered the ACT 2 extension. During the extension, patients continued to receive REMICADE 5 mg/kg or REMICADE 10 mg/kg every 8 weeks. Patients in the extension trials were assessed using the PGA, which is 1 of 4 measures of disease activity included in the Mayo score. Of these 229 patients who entered the extension, 181 have been followed through one year, and 92 have completed two years. Patients who had responded to placebo also enrolled in the extension to maintain the blind and continued to receive placebo every 8 weeks, but were discontinued upon unblinding.
Over the course of the extension trials subjects were allowed to adjust corticosteroid use as required. When corticosteroid use during the extension in all participants (which included subjects previously on corticosteroids and those that had not used corticosteroids) was examined, a smaller proportion of the subjects who had completed follow-up through Weeks 56 and 104 were using corticosteroids. At weeks 8, 56 and 104 of the ACT extension trials, 80 percent, 88 percent and 98 percent of patients, respectively, were corticosteroid-free.
Overall, side effects were generally well tolerated with less than five percent of patients discontinuing therapy due to an adverse event (AE). As previously reported, other notable serious adverse events (SAEs) included: prostate cancer, breast cancer, pneumonia, sarcoidosis, abscess and a death following Histoplasmosis pneumonia (See Important Safety Information below.)
About the Survey
The survey findings were determined through telephone research conducted with 1,000 people with UC. Survey respondents were identified through an opt-in database of more than 17 million United States consumers who requested health information based on their condition profile, of which 40,000 self-reported having UC. Of these 40,000 potential respondents, approximately 19,000 had confirmable contact information. Contact was attempted with 7,900 with a response rate of 13 percent or a total of 1,000 patients. The survey consisted of an interview lasting about 27 minutes, and information was gathered regarding disease severity and employment characteristics.
About Ulcerative Colitis
UC, a chronic inflammatory bowel disease affecting nearly 500,000 people in the U.S., is marked by the inflammation and ulceration of the colonic mucosa, or innermost lining, which causes bloody stools, severe diarrhea and frequent abdominal pain. Tiny open sores, or ulcers, form on the surface of the lining where they bleed and produce pus and mucus. Because the inflammation makes the colon empty frequently, symptoms often lead to unwanted weight loss, blood loss and a host of secondary complications. UC is a chronic disease, and there is no cure. Although progress has been made in IBD research, investigators do not know what causes this disease.
REMICADE is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies and is the only anti-TNF-alpha treatment approved in three different therapeutic areas: gastroenterology, rheumatology and dermatology. REMICADE has demonstrated broad clinical utility in Crohn's disease (CD), rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), ulcerative colitis (UC), pediatric Crohn's disease (PCD) and psoriasis (PsO). The safety and efficacy of REMICADE have been well established in clinical trials over the past 14 years and with more than 843,000 patients treated worldwide through commercial experience.
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 reducing signs and symptoms and inducing and maintaining clinical remission in adult and pediatric 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 adult patients with fistulizing CD. In December 2004, REMICADE was approved for reducing signs and symptoms in patients with active AS. In May 2005, REMICADE was approved for reducing signs and symptoms of active arthritis in patients with PsA. Additionally, in September 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. In addition, on May 19, 2006, REMICADE was approved for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy. This approval establishes REMICADE as the first and only biologic therapy approved for the treatment of PCD. In August 2006, REMICADE received the expanded indication for inhibiting the progression of structural damage and improving physical function in patients with psoriatic arthritis. In September 2006, REMICADE was approved for the treatment of adult patients with chronic severe plaque psoriasis. In October 2006, REMICADE was approved for maintaining clinical remission and mucosal healing in patients with moderately to severely active UC, who have had an inadequate response to conventional therapy.
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), UC (5 mg/kg), PCD (5 mg/kg), and PsO (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
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 TB 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, flu or warm, red or painful skin while taking REMICADE, tell your doctor right away. Also, tell your doctor if you are scheduled to receive a vaccine or if you have lived in a region where histoplasmosis or coccidioidomycosis is common.
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, psoriatic arthritis, or plaque psoriasis 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. Children and young adults who have been treated for Crohn's disease with REMICADE have developed a rare type of lymphoma that often results in death. These patients also were receiving drugs known as azathioprine or 6-mercaptopurine. 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 or if you have a lung disease called chronic obstructive pulmonary disease (COPD).
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, swelling of your ankles or feet, or sudden weight gain).
Reactivation of hepatitis B virus has been reported in patients who are carriers of this virus and are taking TNF blockers, such as REMICADE. Some of these cases have been fatal. Tell your doctor if you know or think you may be a carrier of hepatitis B virus or if you experience signs of hepatitis B infection, such as feeling unwell, poor appetite, tiredness, fever, skin rash and/or joint pain.
There have been rare cases of serious liver injury in people taking REMICADE, some fatal. Tell your doctor if you have liver problems and 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, visual disturbances or seizures while taking REMICADE.
Allergic reactions, some severe, have been reported during or after infusions with REMICADE. Signs of an allergic reaction include hives, difficulty breathing, chest pain, high or low blood pressure, swelling of face and hands, and fever or chills. Tell your doctor if you have experienced a severe allergic reaction. The most common side effects of REMICADE are: respiratory infections, such as sinus infections and sore throat, headache, rash, coughing, and stomach pain.
Please read the Medication Guide for REMICADE and discuss it with your doctor.
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About Digestive Disease Week
DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract, DDW takes place May 19-24, 2007, at the Washington Convention Center, Washington, DC. The meeting showcases approximately 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. For more information, visit www.ddw.org.