Data from SONIC Trial Showed REMICADE Therapy is More Likely to Induce
Steroid-Free Remission and Mucosal Healing Compared with Standard
ORLANDO, Fla., Oct. 6 /PRNewswire/ -- Data presented for the first time from the Phase 3b Study of Patients with Crohn's Disease Naive to Immunomodulators and Biologic Therapy (SONIC) may provide new insights into the approach to care of patients with moderate to severe Crohn's disease. According to findings from the SONIC trial, a significantly greater proportion of patients with moderate to severe Crohn's disease receiving REMICADE(R) (infliximab), either in combination with azathioprine or as monotherapy, experienced steroid-free remission and mucosal healing compared with patients receiving azathioprine alone. Azathioprine is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of Crohn's disease; however, it is widely used by gastroenterologists and other physicians in the United States to treat patients with Crohn's disease. Azathioprine is approved for the treatment of Crohn's disease in some countries outside the United States. Investigators reported that at week 26, 57 percent of patients receiving REMICADE combination therapy and 44 percent of patients receiving REMICADE monotherapy achieved steroid-free remission, the primary endpoint of the study, compared with 31 percent of patients receiving azathioprine alone (P < 0.001 REMICADE with azathioprine vs. azathioprine monotherapy; P = 0.009 REMICADE monotherapy vs. azathioprine monotherapy; P = 0.022 REMICADE with azathioprine vs. REMICADE monotherapy).
"Findings from the SONIC trial have the potential to challenge the treatment protocol for Crohn's disease as these data show that introducing REMICADE earlier may result in more patients achieving steroid-free remission and complete mucosal healing," said Dr. Jean-Frederic Colombel, Professor of Hepatogastroenterology, Centre Hospitalier Universitaire Lille, France and lead investigator. "These data reinforce the efficacy and safety profile of REMICADE in the treatment of this chronic inflammatory bowel disease."
Dr. William J. Sandborn, Inflammatory Bowel Disease Clinic, Mayo Clinic, and principal investigator for the SONIC trial will present the results of the SONIC trial on Tuesday, October 7 at the annual meeting of the American College of Gastroenterology.
The SONIC clinical trial, the first of its kind to compare REMICADE, an anti-tumor necrosis factor (TNF)-alpha therapy, with an immunomodulator in patients with moderate to severe Crohn's disease previously failing 5-aminosalicylate (5-ASA) and/or steroids, included more than 500 subjects from clinics across the United States, Europe and Israel. In addition to improved rates of steroid-free remission in patients receiving REMICADE, the data showed that a greater proportion of patients with Crohn's disease achieved mucosal healing, a secondary endpoint of the study, when receiving REMICADE. Results from SONIC revealed that 44 percent of patients receiving REMICADE combination therapy and 30 percent receiving REMICADE monotherapy achieved mucosal healing compared with 17 percent of patients receiving azathioprine alone (P < 0.001 REMICADE with azathioprine vs. azathioprine monotherapy; P = 0.023 REMICADE monotherapy vs. azathioprine monotherapy; P = 0.055 REMICADE with azathioprine vs. REMICADE monotherapy).
The data also showed that the safety profile of REMICADE in combination or as monotherapy was similar to that of azathioprine monotherapy in the study. At week 30, 24 percent of patients receiving azathioprine monotherapy experienced one or more serious adverse events compared with 16 and 14 percent of patients receiving REMICADE monotherapy and REMICADE with azathioprine, respectively. That includes 2 patients receiving azathioprine monotherapy who developed colon cancer, one patient receiving azathioprine monotherapy who died following a colectomy and one patient receiving REMICADE combination therapy who was diagnosed with tuberculosis. Serious infections were reported as follows: 8 in the azathioprine monotherapy group, 4 in the REMICADE monotherapy group and 6 in the REMICADE combination therapy group.
In 1998 REMICADE became the first anti-TNF-alpha therapy approved by the FDA for the treatment of moderately to severely active Crohn's disease for the reduction of the signs and symptoms in patients who have an inadequate response to conventional therapy. During the past decade, REMICADE has also become the first and only anti-TNF-alpha therapy that the FDA has approved for the treatment of ulcerative colitis, a related inflammatory bowel disease, and pediatric Crohn's disease.
Crohn's disease is a chronic inflammatory disease of the colon and large intestine that affects approximately 500,000 people in the United States. Crohn's disease can lead to frequent hospitalizations, surgery and loss of work productivity.
SONIC is a multicenter, Phase 3b, randomized, double-blind, controlled clinical trial designed to compare the efficacy and safety of REMICADE monotherapy, azathioprine monotherapy and combination therapy with the 2 drugs in patients with moderate to severe Crohn's disease who were nave to immunomodulator and biologic therapy. A total of 508 patients with Crohn's disease who were naive to both biologics and immunomodulators (azathioprine, 6-mercaptopurine and methotrexate) were enrolled in the study and were randomized into three groups; 170 patients received azathioprine 2.5 mg/kg/day and placebo infusions, 169 patients received REMICADE 5 mg/kg infusions at weeks 0, 2, 6 and every 8 weeks thereafter with placebo capsules and 169 patients received REMICADE 5 mg/kg and azathioprine 2.5 mg/kg through 30 weeks. The primary endpoint of SONIC was to assess the induction of steroid-free remission. Fifty-two percent of patients enrolled in SONIC were male and patients had a median age of 34-years-old, median weight of 70 kg, median disease duration of 2.3 years and median baseline Crohn's Disease Activity Index (CDAI) score of 275. Forty-nine percent of patients enrolled in SONIC had extra-intestinal manifestations, 18 percent had a history of fistulas, 21 percent had bowel resections, 27 percent had been hospitalized at least once in the year prior to enrollment because of their Crohn's disease and 41 percent of patients were taking steroids at baseline.
The safety profiles were similar across all 3 treatment groups. No new safety issues were identified. See "Important Safety Information" below.
About Crohn's Disease
Crohn's disease, a chronic inflammatory disease of the gastrointestinal tract, affects approximately 500,000 Americans, including approximately 150,000 pediatric patients. The cause of Crohn's disease is not known, but the disease is associated with abnormalities of the immune system that could be triggered by a genetic predisposition or diet and other environmental factors. Symptoms of Crohn's disease can vary but often include abdominal pain and tenderness, frequent diarrhea, rectal bleeding, weight loss and fever. There is currently no cure for Crohn's disease.
REMICADE is the global market leader among anti-tumor necrosis factor
alpha (TNF-alpha) therapies and is first anti-TNF-alpha treatment to be
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 16 years and through commercial experience with more than one 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
-- 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. 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. REMICADE is a two-hour infusion administered every 6 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.
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 also have 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 important information about REMICADE, including full U.S. prescribing information and Medication Guide, at http://www.remicade.com.
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