HORSHAM, Pa., Oct. 25 /PRNewswire/ -- New data show that nearly 90 percent of pediatric patients with moderate to severe active Crohn's disease (CD) with an inadequate response to conventional therapy achieved clinical response at week 10 when treated with REMICADE(R) (infliximab). Nearly two-thirds of these patients maintained that response through one year when they continued receiving REMICADE every 8 weeks. Moreover, more than half of the patients treated with REMICADE every 8 weeks were in clinical remission at the end of one year. The results of the REACH (A Randomized, Multicenter, Open-label Study to Evaluate the Safety and Efficacy of Anti-TNF Monoclonal Antibody REMICADE in Pediatric Subjects with Moderate to Severe Crohn's Disease) trial are the first Phase 3 results to show the efficacy of a biologic therapy for children with moderate to severe active CD. The data were presented at the annual meeting of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN).
"These results are extremely encouraging for physicians, patients and their families, as current treatment options for children with CD are very limited," said Jeffrey S. Hyams, M.D., professor of pediatrics, University of Connecticut, and head of the Division of Digestive Diseases and Nutrition at Connecticut Children's Medical Center. "The facts that nearly 90 percent of children achieved clinical response at week 10 after receiving the REMICADE induction regimen and that, on the REMICADE maintenance regimen of every 8 weeks, close to two-thirds of children maintained clinical response and more than half achieved clinical remission at week 54, constitute significant findings."
REMICADE has received a Fast Track Designation from the U.S. Food and Drug Administration (FDA) for the treatment of moderately to severely active pediatric Crohn's disease, a chronic inflammatory disease of the gastrointestinal tract that affects nearly 100,000 children under the age of 18 in the United States. The FDA's Fast Track regulations, based upon the FDA Modernization Act of 1997, are designed to facilitate development and expedite review of products that may treat serious or life-threatening diseases and address an unmet medical need. Development programs receiving Fast Track Designations typically receive FDA Priority Review (6-month vs. standard 10- month review). There are currently no FDA-approved biologic therapies to treat moderately to severely active pediatric CD. REMICADE is not currently indicated for the treatment of pediatric CD, and the results of the REACH trial will be included in a supplemental Biologics License application (sBLA) to the FDA in the near future.
Data from the REACH trial showed that 88.4 percent of patients treated with REMICADE 5 mg/kg at 0, 2 and 6 weeks, achieved the primary endpoint of the trial, clinical response at week 10, which was defined as a decrease of more than or equal to 15 in the Pediatric Crohn's Disease Activity Index (PCDAI), and a PCDAI value less than or equal to 30. Patients receiving the REMICADE maintenance regimen of every 8 weeks demonstrated a significantly greater level of improvement in clinical response and remission than those receiving REMICADE maintenance every 12 weeks, a comparison made to better understand the most appropriate pediatric dosing regimen. Sixty-three percent of patients (33 of 52) receiving REMICADE every 8 weeks maintained clinical response after one year of treatment compared with 33 percent of patients (17 of 51) receiving maintenance therapy every 12 weeks (P = 0.002). After 54 weeks of treatment, 56 percent of patients (29 of 52) receiving REMICADE maintenance every 8 weeks were in clinical remission, as assessed by a PCDAI score of less than or equal to 10, compared with 24 percent (12 of 51) in the every 12-week maintenance group (P < 0.001).
Additionally, some patients in the trial were able to reduce their corticosteroid dose. At baseline, the median average daily corticosteroid dose of patients who were receiving corticosteroids was 0.4 mg/kg/day. By week 10, almost half of patients had discontinued corticosteroids, an important step for many with CD who may experience side effects as a result of corticosteroids. The median change from baseline in average daily corticosteroid use at weeks 10, 30 and 54 were -0.2, -0.3 and -0.3, respectively. The change from baseline in average daily corticosteroid use was significant (P<0.001 for all comparisons).
REMICADE's efficacy in the treatment of inflammatory bowel disease is well established in adults. First approved in 1998 in the United States for CD, REMICADE remains the only anti-tumor necrosis factor (TNF-alpha) therapy indicated for the treatment of moderately to severely active CD in patients who have had an inadequate response to conventional therapy. Additionally, REMICADE was recently approved for the treatment of moderately to severely active ulcerative colitis (another type of inflammatory bowel disease) in patients who have had an inadequate response to conventional therapy. The serious adverse events reported in these trials were similar to those reported in previous REMICADE clinical trials. (See Important Safety Information below).
About Pediatric Crohn's
Crohn's disease is a chronic illness affecting an estimated 100,000 people under the age of 18. Crohn's disease causes inflammation of the gastrointestinal tract, typically resulting in symptoms such as diarrhea, fever, abdominal pain and weight loss. Children with Crohn's disease may also experience delayed development and stunted growth. Although it can involve any area of the gastrointestinal tract from the mouth to the anus, it most commonly affects the small intestine and/or colon.
About REACH
REACH was a randomized, multicenter, open-label study designed to evaluate the safety and efficacy of REMICADE in pediatric patients with moderate to severe CD. Patients (n=112) aged 6 to 17 years with moderately to severely active CD despite treatment with an immunomodulator +/- corticosteroids received REMICADE 5 mg/kg at week 0, 2 and 6. One hundred three patients were randomized at week 10 to receive REMICADE every 8 weeks (n=52) or every 12 weeks (n=51) through week 46. Ninety-nine of the 112 patients were in clinical response at week 10. Patients who lost response in the maintenance phase were eligible for a higher or more frequent dose of REMICADE. Baseline demographic and disease characteristics were similar between groups. The median patient age was 13 years.
The primary endpoint of the trial was the percentage of patients who achieved clinical response to induction therapy after 10 weeks (defined as a decrease of greater than or equal to 15 in PCDAI and a PCDAI value of less than or equal to 30). Secondary efficacy endpoints included clinical response at week 54 and clinical remission at weeks 10 and 54.
About REMICADE
REMICADE is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies and has demonstrated broad clinical utility in CD, rheumatoid arthritis (RA), psoriatic arthritis, ulcerative colitis and ankylosing spondylitis. 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 United States, 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 ankylosing spondylitis. On May 13, 2005, REMICADE was approved for reducing signs and symptoms of active arthritis in patients with psoriatic arthritis. 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 and CD, REMICADE is a 2-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 ankylosing spondylitis, REMICADE is a two-hour infusion (5 mg/kg) administered every 6 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6. In UC, REMICADE is a 2-hour infusion (5 mg/kg) administered every 8 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 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, +1-215-325-4010 or Cell:+1-215-983-8000
Web site: http://www.remicade.com//
