Results from the ACT trials showed that significantly more patients treated with REMICADE experienced clinical remission compared to patients given a placebo infusion. REMICADE, was recently approved by the FDA for the treatment of moderately to severely active ulcerative colitis (UC) in patients who have had an inadequate response to conventional therapy. It is the first and only biologic therapy approved for UC and Crohn's disease (CD), both chronic inflammatory bowel diseases (IBDs).
The analysis presented today compares all patients in all treatment arms who achieved remission to all patients in all treatment arms who did not achieve remission. This analysis does not compare REMICADE to controls in terms of employment status.
"It is important to examine the potentially significant impact of UC on patients' employment and the overall cost and burden of their disease," said Dr. William Sandborn, professor of medicine, Mayo College of Medicine; head, IBD Interest Group; director, IBD Clinical Research Unit, Mayo Medical Center and lead study investigator. "Clinical remission is a critical therapeutic goal for UC patients, both in terms of overall health as well as their ability to maintain productive lives."
The analysis of the ACT 1 and ACT 2 clinical data revealed that, at baseline, 35 percent of the 727 patients (n=257) in the studies were not employed and 7.0 percent (n=51) were receiving disability compensation. Among patients not employed at baseline, a significantly greater percentage of those in clinical remission at week 30 and week 54 were employed, compared to patients not in clinical remission [week 30 (ACT 1and 2): 20.6 percent vs. 8.3 percent, P<0.05; week 54 (ACT 1): 30.4 percent vs. 8.8 percent, P<0.05].
In addition, of patients receiving disability compensation at the start of the trials, greater percentages of those in clinical remission at weeks 30 and 54 were no longer receiving disability compensation compared to those not in clinical remission [week 30 (ACT 1and 2): 58.8 percent vs. 20.0 percent; week 54 (ACT 1): 80.0 percent vs. 16.7 percent].
Clinical Trial Information: ACT 1 and ACT 2
REMICADE was recently approved by the FDA for the treatment of UC based on positive results from two randomized, placebo-controlled, pivotal Phase 3 clinical trials, ACT 1 and ACT 2. The trials were conducted to evaluate the safety and efficacy of REMICADE in patients with moderate to severely active UC.
In each trial, 364 patients with active UC who were unresponsive to at least one standard therapy©¤ including corticosteroids, immunosuppressants or 5-ASAs©¤ were enrolled. Patients in ACT 1 and ACT 2 had evidence of moderate or severe UC (total Mayo score of 6 to 12 and an endoscopy score >2). In both trials, patients were randomized to one of three groups: continued conventional therapy plus placebo infusions, continued conventional therapy plus infliximab 5 mg/kg infusions or continued conventional therapy plus infliximab 10 mg/kg infusions. ACT 1 patients received the study agent at weeks 0, 2 and 6 and then every 8 weeks through week 46 and had their last evaluations at week 54. ACT 2 patients received the study agent at weeks 0, 2 and 6 and then every 8 weeks through week 22 and had their last evaluations at week 30.
In ACT 1, significantly higher proportions of patients receiving REMICADE 5 mg/kg (69 percent) and 10 mg/kg (62 percent) achieved clinical response at week 8 versus patients receiving placebo infusions (37 percent; P <0.001 for both). In addition, at week 30, 52 percent of patients in the 5 mg/kg and 51 percent of patients in the 10 mg/kg REMICADE treatment group were in clinical response versus 30 percent of placebo infusion group (P <0.001 and P <0.01, respectively). At week 8, 39 percent and 32 percent of patients treated with REMICADE 5 mg/kg and 10 mg/kg, respectively, were in clinical remission compared to 15 percent of the placebo infusion group (P <0.001 and P <0.01). These differences in remission rates persisted at week 30 (34 percent, 5 mg/kg; 37 percent, 10 mg/kg versus 16 percent, placebo; P <0.001 for both). Mucosal healing was achieved at week 8 in 62 percent and 59 percent of patients receiving REMICADE 5 mg/kg and 10 mg/kg, respectively, versus 34 percent of patients given placebo infusions (P <0.001). This difference in mucosal healing was maintained at week 30 (50 percent, 5 mg/kg; 49 percent, 10 mg/kg versus 25 percent, placebo; P <0.001 for both). The proportion of patients who were able to discontinue corticosteroids while in clinical remission at week 30 was greater in both REMICADE groups compared to the placebo infusion group (24 percent, 5 mg/kg; 19 percent, 10 mg/kg; 10 percent, placebo; P =0.030 and P =0.125, respectively).
In ACT 2, significantly higher proportions of patients receiving REMICADE 5 mg/kg (65 percent) and 10 mg/kg (69 percent) were in clinical response at week 8 versus 29 percent who received placebo infusions (P <0.001 for both). At week 30, 47 percent of patients receiving REMICADE 5 mg/kg and 60 percent receiving 10 mg/kg were in clinical response versus 26 percent of patients receiving placebo infusions (P <0.001 for both). Clinical remission was achieved at week 8 in 34 percent and 28 percent of REMICADE 5 and 10 mg/kg patients, respectively, compared to 6 percent of the placebo infusion group (P <0.001 for both).
Differences in remission rates persisted at week 30 (26 percent, 5 mg/kg; 36 percent, 10 mg/kg; 11 percent, placebo; P <0.01 and P <0.001). Mucosal healing was achieved at week 8 in 60 percent and 62 percent of patients receiving REMICADE 5 mg/kg and 10 mg/kg, respectively, compared to 31 percent of patients receiving placebo infusions (P <0.001 for both). Mucosal healing at week 30 was achieved in 46 percent and 57 percent of patients receiving REMICADE 5 and 10 mg/kg, respectively, compared to 30 percent of the placebo infusion group (P <0.01 and P <0.001). The proportion of patients who were able to discontinue corticosteroids while in clinical remission at week 30 was significantly greater in both REMICADE groups compared with the placebo infusion group (18 percent, 5 mg/kg; 27 percent, 10 mg/kg; 3 percent, placebo; P =0.010 and P <0.001, respectively).
The serious adverse events reported in these trials were similar to those reported in previous REMICADE clinical trials. (See Important Safety Information below).
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, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract, DDW takes place May 20-25, 2006, at the Los Angeles Convention Center. 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.
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 13 years and through commercial experience with over 700,000 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 moderate 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. 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.
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.
Centocor discovered REMICADE and has exclusive marketing rights to the product in the United States. Schering-Plough markets REMICADE in all countries outside of the United States, except in Japan and parts of the Far East where Tanabe Seiyaku, Ltd. markets the product and in China where Xian-Janssen markets REMICADE.
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.
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. 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).
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.
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.
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.