Remicade Study Results Show Greater Steroid-Free Remission and Mucosal Healing Compared With Conventional Immunomodulator Azathioprine in Treatment of Crohn's Disease
Findings Published in Today's New England Journal of Medicine
HORSHAM, Pa., April 15 /PRNewswire/ -- Findings published today
in The New England Journal of Medicine from a first-of-its-kind
comparator trial evaluating the anti-tumor necrosis factor
(TNF)-alpha biologic treatment REMICADE (infliximab) in the
treatment of moderately to severely active Crohn's disease in
patients who were naive to immunomodulator and biologic therapy,
showed that a significantly greater proportion of patients
receiving REMICADE achieved steroid-free remission and mucosal
healing compared with patients receiving azathioprine.
The results of the Phase 4 Study of Biologic and Immunomodulator
Naive Patients in Crohn's (SONIC) clinical trial published in
today's New England Journal of Medicine is the first of its kind to
compare REMICADE, an anti-TNF-alpha therapy, with an
immunomodulator (azathioprine) in patients with moderate to severe
Crohn's disease. Azathioprine (AZA) is not approved by the United
States Food and Drug Administration (FDA) for the treatment of
Crohn's disease; however, it is widely used by gastroenterologists
and other physicians in the U.S. to treat patients with Crohn's
disease. Azathioprine is approved for the treatment of Crohn's
disease in some countries outside the U.S.
Crohn's disease is a chronic inflammatory disease of the
gastrointestinal tract that affects approximately 500,000
Americans. Symptoms of the disease can vary but often include
abdominal pain and tenderness, frequent diarrhea, rectal bleeding,
weight loss and fever. The cause of Crohn's disease is not
known.
"As the first trial to compare an anti-TNF therapy with an
immunomodulator in patients who have failed 5-ASA and/or steroids,
the SONIC trial has the potential to change how we currently treat
patients with moderate to severe Crohn's disease," said Dr.
Jean-Frederic Colombel, Professor of Hepatogastroenterology, Centre
Hospitalier Universitaire de Lille (France) and principal
investigator. "The results provide new insights into the benefits
of starting REMICADE alone or in combination with azathioprine --
earlier in the treatment of moderate to severe Crohn's
disease."
Investigators reported that at the week 26 primary endpoint of
the trial, 57 percent of patients receiving REMICADE combination
therapy (REMICADE and azathioprine together) and 44 percent of
patients receiving REMICADE monotherapy achieved steroid-free
remission compared with 30 percent of patients receiving
azathioprine alone (P<0.001 REMICADE with azathioprine vs.
azathioprine monotherapy; P=0.006 REMICADE monotherapy vs.
azathioprine monotherapy; P=0.02 REMICADE with azathioprine vs.
REMICADE monotherapy).
In addition to improved rates of steroid-free remission in
patients receiving REMICADE, the data showed that a greater
proportion of patients receiving REMICADE achieved mucosal healing
(i.e. complete absence of mucosal ulceration at week 26 in patients
with mucosal ulcerations at baseline) a secondary endpoint of the
study. Forty-four 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=0.02 REMICADE monotherapy vs.
azathioprine monotherapy; P=0.06 REMICADE with azathioprine vs.
REMICADE monotherapy). The P values for all secondary endpoints
should be considered nominal since no adjustments were made for
multiple comparisons.
Patients participating in the SONIC study through 30 weeks were
given the option of continuing in a blinded study extension through
50 weeks. At week 50, REMICADE showed similar significant
therapeutic benefit over azathioprine 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. Through 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. This includes two 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 in 6 percent of
patients in the azathioprine monotherapy group, 5 percent in the
REMICADE monotherapy group and 4 percent in the REMICADE
combination therapy group.
A final safety analysis for the entire study included data
through week 54. The proportion of patients with one or more
serious adverse events during the study was 27 percent (n=43) in
the AZA monotherapy treatment group, 24 percent (n=39) in the
REMICADE monotherapy treatment group and 15 percent (n=27) in the
combined REMICADE and AZA treatment group. No new serious adverse
events, such as opportunistic infections, malignancies or death,
were reported between weeks 30 and 54.
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 approved by the FDA for the
treatment of moderately to severely active ulcerative colitis, in
patients with an inadequate response to conventional therapy, a
related inflammatory bowel disease. REMICADE is also approved for
the treatment of pediatric patients with moderately to severely
active Crohn's disease who have had an inadequate response to
conventional therapies.
The SONIC study was supported by Centocor Ortho Biotech Inc. About SONIC
SONIC was a multicenter, Phase 4, 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 moderately to
severely active Crohn's disease who were naive to immunomodulator
and biologic therapy. A total of 508 patients from the U.S., Europe
and Israel were enrolled in the study and were randomized into
three groups; 170 patients received azathioprine less than or equal
to 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 at weeks 0, 2, 6 and every 8 weeks thereafter and
azathioprine less than or equal to 2.5 mg/kg/day. The primary
endpoint of SONIC was to assess the induction of steroid-free
remission at week 26. 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.
Patients completing treatment through week 30, and who, in the
opinion of the investigator, may benefit from continued treatment,
entered into the study extension beginning at week 30 through week
50.
For more information regarding the safety profile for REMICADE,
please 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.
About REMICADE
REMICADE was the first anti-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 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
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.
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), 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. The company was formed when
Centocor, Inc. and Ortho Biotech Inc. were consolidated in late
2008, and was renamed Centocor Ortho Biotech Inc. 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.
Source: Centocor Ortho Biotech, Inc.
CONTACT: Craig Stoltz of Centocor Ortho Biotech, Inc.,
+1-215-325-3612,
Cell, +1-215-779-9396; Investor Relations: Tina Pinto of Johnson
& Johnson,
+1-732-524-2034
Web Site: http://www.centocororthobiotech.com/
Posted: April 2010
