New Phase 3 Study Results Show REMICADE® is Effective in the Treatment of Pediatric Patients With Moderate to Severe Ulcerative Colitis

CHICAGO, May 9, 2011 /PRNewswire/ -- Data from a Phase 3 randomized, multicenter, open-label study demonstrated clinical response with REMICADE® (infliximab) in the treatment of pediatric patients with moderately to severely active ulcerative colitis (UC), and showed a safety profile consistent with previous clinical trials conducted in an adult population.  The pediatric UC findings, presented today at Digestive Disease Week, showed REMICADE induced clinical response in 73 percent of patients aged 6-17 years at week 8, the primary endpoint of the trial.  REMICADE received U.S. Food and Drug Administration (FDA) approval for the treatment of adults with moderately to severely active UC in September 2005 and in October 2006, REMICADE received FDA approval for maintaining clinical remission and mucosal healing indications in adults living with UC.

UC is a chronic inflammatory bowel disease (IBD) of the colon.  It is estimated that 1.4 million Americans have IBD with the number evenly split between UC and Crohn's disease.  An estimated 150,000 children under age 17 are living with debilitating symptoms of IBD.(1)  

"The results of this study are consistent with findings from the Active Ulcerative Colitis (ACT) trials, which evaluated REMICADE in the treatment of adults with ulcerative colitis," said Jeffrey Hyams, Head of the Division of Digestive Diseases and Nutrition at Connecticut Children's Medical Center and Professor of Pediatrics at University of Connecticut School of Medicine, and lead study investigator.  "UC can be a devastating disease, particularly for children and adolescents.  It is encouraging to see such promising results in a patient population that is in need of additional treatment options."

In December 2010, Centocor Ortho Biotech Inc. submitted a supplemental Biologics License Application (sBLA) to the FDA requesting the approval of REMICADE (infliximab) for the treatment of moderately to severely active UC in pediatric patients who have had an inadequate response to conventional therapy. The REMICADE pediatric UC sBLA was designated priority review by the FDA. On November 12, 2003, the FDA designated REMICADE orphan drug status for the treatment of pediatric UC.

A total of 60 patients with moderately to severely active UC (Mayo score of 6-12, with an endoscopy subscore more than or equal to 2) were enrolled in the trial.  Patients had previously failed to respond to or tolerate treatment with 6-mercaptopurine (6-MP), azathioprine (AZA), corticosteroids, and/or 5-aminosalicylate (5-ASA) and were administered REMICADE 5 mg/kg at weeks 0, 2, and 6.  At week 8, REMICADE induced clinical response according to the Mayo score in 73.3 percent of patients, the primary endpoint of the trial.  The Mayo score is a 12-point clinical assessment and colonoscopy-based measure of disease activity.   Also at week 8, 40 percent of patients were in clinical remission by the Mayo score and 33.3 percent were in remission by the validated, non-invasive clinical assessment of disease activity in children, the Pediatric UC Activity Index (PUCAI).  In addition, 68.3 percent of patients achieved mucosal healing at week 8.

Patients achieving clinical response at week 8 (n=45) were randomized to receive REMICADE 5 mg/kg every eight weeks through week 46 (n=22) or every 12 weeks through week 42 (n=23).  At week 54, twice as many patients in the group that received REMICADE every eight weeks (38.1 percent) achieved remission by the PUCAI compared with the group that received REMICADE every 12 weeks (18.2 percent), though this did not reach statistical significance (P = 0.146) due to the small sample sizes.  More patients on corticosteroids at baseline were in remission and off corticosteroids at week 54 in the maintenance group that received REMICADE every eight weeks (38.5 percent) than in the every 12-week maintenance group (0 percent).

About the Study

The Phase 3 randomized, multicenter, open-label trial was designed to evaluate the efficacy of a 3-dose REMICADE regimen in inducing clinical response in pediatric patients with moderately to severely active UC and to evaluate the safety of REMICADE during induction and maintenance treatment.  A total of 60 patients, aged 6-17, with a median disease duration of 1.4 years were included in the study.  Patients had a median Mayo score of 8.0, and median PUCAI score of 55.  All patients had failed to respond to or tolerate treatment with 6-MP, AZA, corticosteroids and/or 5-ASA.  Patients received REMICADE 5 mg/kg at weeks 0, 2, and 6.  The primary endpoint, clinical response at week 8, was defined as a decrease from baseline in the Mayo score of at least 30 percent and at least 3 points, with a decrease in rectal bleeding subscore of at least 1 or a rectal bleeding subscore of 0/1.  Patients who achieved clinical response at week 8 were randomized to receive REMICADE 5 mg/kg every 8 weeks through week 46 or every 12 weeks through week 42.  Non-responders were discontinued from study agent.  

REMICADE was generally well tolerated.  The proportions of patients experiencing serious adverse events were similar across the maintenance groups (18.2% and 21.7% in the every 8 week and every 12 week groups, respectively).  Similarly the proportions of patients experiencing infusion reactions were also similar (18.2% and 13.0% in the every 8 week and every 12 week groups, respectively).  No deaths, malignancies, opportunistic infections, tuberculosis or delayed hypersensitivity reactions were reported.

For more information regarding the safety profile for REMICADE, please see "Important Safety Information" below.  

About Ulcerative Colitis

Ulcerative colitis (UC), a chronic inflammatory bowel disease affecting nearly 700,000 people in the U.S., is marked by the inflammation and ulceration of the colonic mucosa, or innermost lining, which may lead to 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.  Symptoms of the disease may lead to loss of appetite, subsequent weight loss, and fatigue.  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.

About REMICADE

REMICADE was the first anti-tumor necrosis factor (TNF)-alpha treatment to be approved in three different therapeutic areas: gastroenterology, rheumatology and dermatology.  REMICADE has demonstrated broad clinical utility with indications 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 17 years and through commercial experience with more than 1.3 million patients treated worldwide.

In the U.S., REMICADE is approved for the following indications:

• Reducing signs and symptoms, inhibiting the progression of structural damage and improving physical function in patients with moderately to severely active RA, when administered in combination with methotrexate.  
• Reducing signs and symptoms in patients with active AS.
• 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.  
• Reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing CD.  
• Reducing signs and symptoms, inducing and maintaining 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.
• Reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage and improving physical function in patients with PsA.  
• Treatment of adult patients with chronic severe plaque PsO who are candidates for systemic therapy and when other systemic therapies are medically less appropriate.

REMICADE is unique among available anti-TNF biologic therapies.  It is the only anti-TNF biologic administered directly by caregivers in the clinic or office setting.  REMICADE is a two-hour infusion administered every 4 or 8 weeks (indication-dependent), 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 as maintenance therapy.

Centocor Ortho Biotech Inc. discovered and developed REMICADE and has exclusive marketing rights to the product in the United States.  

Important Safety Information  

Only a doctor can recommend a course of treatment after checking a patient's health condition. REMICADE® (infliximab) can cause serious side effects such as lowering your ability to fight infections.  There are reports of serious infections caused by viruses, fungi or bacteria that have spread throughout the body, including tuberculosis (TB) and histoplasmosis.  Some of these infections have been fatal.  Your doctor should monitor you closely for signs and symptoms of TB during treatment with REMICADE®.

Unusual cancers have been reported in children and teenage patients taking TNF-blocker medicines. A rare form of fatal lymphoma has occurred mostly in teenage or young adult males with Crohn's disease or ulcerative colitis who were taking REMICADE® and azathioprine or 6-mercaptopurine.  For children and adults taking TNF blockers, including REMICADE®, the chances of getting lymphoma or other cancers may increase.

Patients should discuss any concerns about their health and medical care with their doctor.

Patients should let their doctors know if they have or ever had any of the following:

• Tuberculosis (TB) or have been near someone who has TB. Your doctor will check you for TB with a skin test.  If you have latent (inactive) TB, you will begin TB treatment before you start REMICADE®.
• Lived in a region where certain fungal infections like histoplasmosis or coccidioidomycosis are common.
• Infections that keep coming back, have diabetes or an immune system problem.
• Any type of cancer or a risk factor for developing cancer, for example, chronic obstructive pulmonary disease (COPD) or had phototherapy for psoriasis.
• Heart failure or any heart condition.  Many people with heart failure should not take REMICADE®.
• Hepatitis B virus (HBV) infection or think you may be a carrier of HBV.
• Nervous system disorders (like multiple sclerosis or Guillain-Barre syndrome).

Also tell your doctor about any medications you are taking, including vaccines or Kineret (anakinra), Orencia (abatacept) and Actemra (tocilizumab) and if you are pregnant, plan to become pregnant or are nursing.  Adults and children should not receive a live vaccine while taking REMICADE®.

The following serious (sometimes fatal) side effects have been reported in people taking REMICADE.

Patients should tell their doctors right away if you have any of the signs listed below:

• Infections (like TB, blood infections, pneumonia)—fever, tiredness, cough, flu, or warm, red or painful skin or any open sores.  REMICADE® can make you more likely to get an infection or make any infection that you have worse.
• Lymphoma, or any other cancers in adults and children.  
• Heart failure—new or worsening symptoms, such as shortness of breath, swelling of your ankles or feet, or sudden weight gain.
• Reactivation of HBV—feeling unwell, poor appetite, tiredness, fever, skin rash and/or joint pain.
• Liver injury—jaundice (yellow skin and eyes), dark brown urine, right-sided abdominal pain, fever, or severe tiredness.
• Blood disorders—fever that doesn't go away, bruising, bleeding or severe paleness.
• Nervous system disorders—numbness, weakness, tingling, changes in your vision or seizures.
• Allergic reactions during or after the infusion—hives, difficulty breathing, chest pain, high or low blood pressure, swelling of face and hands, and fever or chills.
• Lupus-like syndrome—chest discomfort or pain that does not go away, shortness of breath, joint pain, rash on the cheeks or arms that gets worse in the sun.  The more common side effects with REMICADE® are respiratory infections (that may include sinus infections and sore throat), headache, rash, coughing and stomach pain.
• Psoriasis—new or worsening psoriasis such as red scaly patches or raised bumps on the skin that are filled with pus.  

Please read important information about REMICADE, including full U.S. prescribing information and Medication Guide, at www.remicade.com.

About Centocor Ortho Biotech Inc.

Centocor Ortho Biotech Inc. redefines the standard of care in immunology, nephrology, and oncology. Built upon a pioneering history, Centocor Ortho Biotech Inc. harnesses innovations in large-molecule and small-molecule research to create important new therapeutic options.  Beyond its innovative medicines, Centocor Ortho Biotech is at the forefront of developing education and public policy initiatives to ensure patients and their families, caregivers, advocates, and healthcare professionals have access to the latest treatment information, support services, and quality care.  For more information about Centocor Ortho Biotech, visit www.CentocorOrthoBiotech.com.  Centocor Ortho Biotech Inc. is a wholly owned subsidiary of Johnson & Johnson.

About DDW

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 7 - 10, 2011, at McCormick Place, Chicago, IL. 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.

References:

(1) Crohn's & Colitis Foundation of America and the Starlight Children's Foundation. Give me some numbers! What are the most current IBD-related statistics? Available at: http://www.ucandcrohns.org/src_subarticle.php?c=&id=2&page=3&tbl=src_faq. Accessed March 20, 2011.

SOURCE Centocor Ortho Biotech Inc.