| Remicade Side Effects Warnings, and Therapeutic Uses |
Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and
Research, noted that there have been no satisfactory treatments for children
with Crohn's disease who have moderate to severe disease activity despite
traditional or conventional therapies. Crohn's disease can cause diarrhea,
cramping, abdominal pain, gastrointestinal bleeding, and in some cases
creates abnormal connections (fistulas) leading from the intestine to the skin.
"Remicade is not a cure, but it provides a much-needed option for reducing
the symptoms and inducing and maintaining disease remission in children
who have no other safe and effective therapy," he said. "We believe that the
potential benefits of this product outweigh the risks that are known and
have been carefully evaluated."
Study
The safety and effectiveness of Remicade in pediatric Crohn's disease were
assessed in a randomized study in 112 children who were 6 to 17 years old
with moderately to severely active Crohn's disease who had an inadequate
response to conventional therapies. The proportion of these patients who
achieved clinical response compared favorably with the proportion of adults
in an earlier Remicade study in adult Crohn's disease, and the pediatric trial's
results showed no new safety concerns not already expressed in the
product's current label.
Side Effects and Risk Factors of Remicade
In general, the safety profile for Remicade in the pediatric trial was similar to
the data that was presented at an FDA Arthritis Advisory Committee meeting
in March 2003, and that dealt with the extent to which anti-TNF therapies
may increase the risk of serious infections and malignancies, such as sepsis
and pneumonia in certain patients.
These risks, which are described in a study in the May 17 issue of the Journal
of the American Medical Association, are included in the current labels for all
approved TNF-alpha blocking agents, including Remicade.
More recently, the FDA has received rare post-marketing reports of an
aggressive and often fatal type of T-cell lymphoma (hepatosplenic T-cell
lymphoma) in adolescent and young adult patients with the Crohn's disease.
In most, but not all cases, these patients were treated with standard
immunosuppressive therapies (azathioprine or 6-mercaptopurine) in
combination with Remicade. The FDA is working with the manufacturer to
address this risk by updating the Warnings sections of the Remicade label.
FDA continues to actively and carefully monitor the safety experience with
Remicade and similar therapies in an effort to maximize their very real
benefits yet limit, to the degree possible, the potential for very serious
toxicities. [1]
What is Crohn's disease?
Crohn's disease is a chronic inflammatory condition of the gastrointestinal
tract that affects adults and children, males and females alike, and can occur
anywhere from the mouth to the anus. The inflammation that occurs often
involves the entire wall of the gastrointestinal tract which can result in
abdominal pain, gastrointestinal bleeding, diarrhea or loose stools, strictures
(blockages), and infections. The majority of patients with Crohn's disease
often require surgery to remove very inflamed or scarred portions of the
gastrointestinal tract. Despite surgery, the disease often recurs; over time,
repeated surgeries may be required. Multiple surgeries can result in patients
becoming debilitated for the rest of their lives and having to live with chronic
diarrhea and requiring supplemental nutrition. [2]
Available treatments for Crohn's disease are primarily directed at reducing
the amount of inflammation in the gastrointestinal tract. The cause of
CrohnÂ’s disease is unknown and there is currently no known cure for it.
Remicade does not cure CrohnÂ’s disease but may reduce gastrointestinal
inflammation by acting against TNF-alpha. [2]
What is Remicade?
Remicade is a biotechnology product and is also known as infliximab. It was
recommended for approval for the treatment of adult Crohn's disease by the
Gastrointestinal Drugs Advisory Committee in May 1998 and licensed in
August 1998. It is a genetically engineered monoclonal antibody that binds
to a protein called tumor necrosis factor-alpha (TNF-alpha). This antibody is
manufactured using cells containing human and mouse antibody genes.
Tumor necrosis factor-alpha plays a key role in the chronic inflammation that
occurs in Crohn's disease and in other diseases that are characterized by
chronic inflammation such as rheumatoid arthritis, psoriatic arthritis,
ankylosing spondylitis, and ulcerative colitis.
Recently, Remicade (infliximab) is being approved to treat children with
CrohnÂ’s disease who have moderately to severely active CrohnÂ’s disease
despite being on traditional or conventional therapies such as
aminosalicylates, steroids, and immunomodulator drugs (e.g., azathioprine
and 6-mercaptopurine). [2]
As part of the initial approval of Remicade in 1998 for adult patients with
CrohnÂ’s disease, Centocor committed to study Remicade in children with
CrohnÂ’s disease.
Remicade has not been studied in children with CrohnÂ’s disease who are
under the age of 6 years. The safety and effectiveness of Remicade in
pediatric CrohnÂ’s disease patients less than 6 years old have not been
established in clinical trials.
Should Remicade be used in everyone with Crohn's
disease?
No. Remicade is currently approved for adults and children with Crohn]s
disease who continue to have very active symptoms of CrohnÂ’s disease
despite having been tried on more conventional therapies (listed above).
Remicade should be prescribed by physicians who are experienced in
treating patients with CrohnÂ’s disease and who feel that the benefits of
Remicade therapy outweigh the risks associated with this treatment.
What are the adverse events that have been
associated with Remicade therapy?
Data from clinical trials and post-marketing reports have identified serious
adverse events associated with Remicade therapy and these adverse events
appear to be related to the effects of the drug. Serious infections, including
tuberculosis and opportunistic infections, have been reported. Some of
these infections have been fatal.
In clinical trials evaluating the use of Remicade in rheumatoid arthritis and
adult CrohnÂ’s disease, there have been more reports of malignancies
including a type of malignancy called lymphoma in patients receiving
Remicade compared to those receiving placebo.
These risks of malignancy and serious infection have been described in
Remicade labeling, and were also the subject of an FDA Arthritis Advisory
Committee meeting in March, 2003
Other side effects that can occur with Remicade therapy include allergic or
infusion reactions, liver injury, worsening of heart failure, hematologic
events, hypersensitivity reactions, and neurologic events.
Physicians who are considering Remicade therapy for their patients should
inform them of the potential adverse events that have been reported in
clinical trials and in post-marketing safety reports.
Are there any safety concerns specific to Crohn's
disease patients who use Remicade?
Analysis of the post-marketing safety database by the FDA identified rare
cases of an aggressive, often fatal form of lymphoma called hepatosplenic T-
cell lymphoma in adolescent and young adult patients with CrohnÂ’s disease
who were treated with Remicade. These patients also had a history of being
treated with the immunomodulator drug called azathioprine. Some of these
patients were only on azathioprine alone. No cases of hepatosplenic T-cell
lymphoma have been identified in patients receiving Remicade alone. The
recent identification of this type of lymphoma resulted in modification to the Â
“boxed warning” and “warnings” sections of the Remicade label to
highlight this aggressive form of lymphoma. The potential role of Remicade in
the development of malignancies is not known. In addition to these changes
to product labeling, the Remicade sponsor has agreed to conduct long-term
follow-up of pediatric patients with Crohn's disease to monitor for this rare
form of lymphoma and for other adverse events.
Does the May 17, 2006 JAMA article raise new safety
concerns about Remicade?
The risks of side effects such as malignancy and serious infection that were
described in the JAMA article have been known and are labeled for all
approved TNF-alpha blocking agents, including Remicade.
[1] FDA Approves Remicade for Children with CrohnÂ’s Disease FDA News
May 19, 2006 [2] Questions and Answers on Remicade/FDA Action May 19,
2006
Research, noted that there have been no satisfactory treatments for children
with Crohn's disease who have moderate to severe disease activity despite
traditional or conventional therapies. Crohn's disease can cause diarrhea,
cramping, abdominal pain, gastrointestinal bleeding, and in some cases
creates abnormal connections (fistulas) leading from the intestine to the skin.
"Remicade is not a cure, but it provides a much-needed option for reducing
the symptoms and inducing and maintaining disease remission in children
who have no other safe and effective therapy," he said. "We believe that the
potential benefits of this product outweigh the risks that are known and
have been carefully evaluated."
Study
The safety and effectiveness of Remicade in pediatric Crohn's disease were
assessed in a randomized study in 112 children who were 6 to 17 years old
with moderately to severely active Crohn's disease who had an inadequate
response to conventional therapies. The proportion of these patients who
achieved clinical response compared favorably with the proportion of adults
in an earlier Remicade study in adult Crohn's disease, and the pediatric trial's
results showed no new safety concerns not already expressed in the
product's current label.
Side Effects and Risk Factors of Remicade
In general, the safety profile for Remicade in the pediatric trial was similar to
the data that was presented at an FDA Arthritis Advisory Committee meeting
in March 2003, and that dealt with the extent to which anti-TNF therapies
may increase the risk of serious infections and malignancies, such as sepsis
and pneumonia in certain patients.
These risks, which are described in a study in the May 17 issue of the Journal
of the American Medical Association, are included in the current labels for all
approved TNF-alpha blocking agents, including Remicade.
More recently, the FDA has received rare post-marketing reports of an
aggressive and often fatal type of T-cell lymphoma (hepatosplenic T-cell
lymphoma) in adolescent and young adult patients with the Crohn's disease.
In most, but not all cases, these patients were treated with standard
immunosuppressive therapies (azathioprine or 6-mercaptopurine) in
combination with Remicade. The FDA is working with the manufacturer to
address this risk by updating the Warnings sections of the Remicade label.
FDA continues to actively and carefully monitor the safety experience with
Remicade and similar therapies in an effort to maximize their very real
benefits yet limit, to the degree possible, the potential for very serious
toxicities. [1]
What is Crohn's disease?
Crohn's disease is a chronic inflammatory condition of the gastrointestinal
tract that affects adults and children, males and females alike, and can occur
anywhere from the mouth to the anus. The inflammation that occurs often
involves the entire wall of the gastrointestinal tract which can result in
abdominal pain, gastrointestinal bleeding, diarrhea or loose stools, strictures
(blockages), and infections. The majority of patients with Crohn's disease
often require surgery to remove very inflamed or scarred portions of the
gastrointestinal tract. Despite surgery, the disease often recurs; over time,
repeated surgeries may be required. Multiple surgeries can result in patients
becoming debilitated for the rest of their lives and having to live with chronic
diarrhea and requiring supplemental nutrition. [2]
Available treatments for Crohn's disease are primarily directed at reducing
the amount of inflammation in the gastrointestinal tract. The cause of
CrohnÂ’s disease is unknown and there is currently no known cure for it.
Remicade does not cure CrohnÂ’s disease but may reduce gastrointestinal
inflammation by acting against TNF-alpha. [2]
What is Remicade?
Remicade is a biotechnology product and is also known as infliximab. It was
recommended for approval for the treatment of adult Crohn's disease by the
Gastrointestinal Drugs Advisory Committee in May 1998 and licensed in
August 1998. It is a genetically engineered monoclonal antibody that binds
to a protein called tumor necrosis factor-alpha (TNF-alpha). This antibody is
manufactured using cells containing human and mouse antibody genes.
Tumor necrosis factor-alpha plays a key role in the chronic inflammation that
occurs in Crohn's disease and in other diseases that are characterized by
chronic inflammation such as rheumatoid arthritis, psoriatic arthritis,
ankylosing spondylitis, and ulcerative colitis.
Recently, Remicade (infliximab) is being approved to treat children with
CrohnÂ’s disease who have moderately to severely active CrohnÂ’s disease
despite being on traditional or conventional therapies such as
aminosalicylates, steroids, and immunomodulator drugs (e.g., azathioprine
and 6-mercaptopurine). [2]
As part of the initial approval of Remicade in 1998 for adult patients with
CrohnÂ’s disease, Centocor committed to study Remicade in children with
CrohnÂ’s disease.
Remicade has not been studied in children with CrohnÂ’s disease who are
under the age of 6 years. The safety and effectiveness of Remicade in
pediatric CrohnÂ’s disease patients less than 6 years old have not been
established in clinical trials.
Should Remicade be used in everyone with Crohn's
disease?
No. Remicade is currently approved for adults and children with Crohn]s
disease who continue to have very active symptoms of CrohnÂ’s disease
despite having been tried on more conventional therapies (listed above).
Remicade should be prescribed by physicians who are experienced in
treating patients with CrohnÂ’s disease and who feel that the benefits of
Remicade therapy outweigh the risks associated with this treatment.
What are the adverse events that have been
associated with Remicade therapy?
Data from clinical trials and post-marketing reports have identified serious
adverse events associated with Remicade therapy and these adverse events
appear to be related to the effects of the drug. Serious infections, including
tuberculosis and opportunistic infections, have been reported. Some of
these infections have been fatal.
In clinical trials evaluating the use of Remicade in rheumatoid arthritis and
adult CrohnÂ’s disease, there have been more reports of malignancies
including a type of malignancy called lymphoma in patients receiving
Remicade compared to those receiving placebo.
These risks of malignancy and serious infection have been described in
Remicade labeling, and were also the subject of an FDA Arthritis Advisory
Committee meeting in March, 2003
Other side effects that can occur with Remicade therapy include allergic or
infusion reactions, liver injury, worsening of heart failure, hematologic
events, hypersensitivity reactions, and neurologic events.
Physicians who are considering Remicade therapy for their patients should
inform them of the potential adverse events that have been reported in
clinical trials and in post-marketing safety reports.
Are there any safety concerns specific to Crohn's
disease patients who use Remicade?
Analysis of the post-marketing safety database by the FDA identified rare
cases of an aggressive, often fatal form of lymphoma called hepatosplenic T-
cell lymphoma in adolescent and young adult patients with CrohnÂ’s disease
who were treated with Remicade. These patients also had a history of being
treated with the immunomodulator drug called azathioprine. Some of these
patients were only on azathioprine alone. No cases of hepatosplenic T-cell
lymphoma have been identified in patients receiving Remicade alone. The
recent identification of this type of lymphoma resulted in modification to the Â
“boxed warning” and “warnings” sections of the Remicade label to
highlight this aggressive form of lymphoma. The potential role of Remicade in
the development of malignancies is not known. In addition to these changes
to product labeling, the Remicade sponsor has agreed to conduct long-term
follow-up of pediatric patients with Crohn's disease to monitor for this rare
form of lymphoma and for other adverse events.
Does the May 17, 2006 JAMA article raise new safety
concerns about Remicade?
The risks of side effects such as malignancy and serious infection that were
described in the JAMA article have been known and are labeled for all
approved TNF-alpha blocking agents, including Remicade.
[1] FDA Approves Remicade for Children with CrohnÂ’s Disease FDA News
May 19, 2006 [2] Questions and Answers on Remicade/FDA Action May 19,
2006
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Equipment
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CONTRACT
MANUFACT.
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NEW DRUGS
Arranon
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Alfuzosin
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Asmanex(R)
Erbitux
(cetuximab)
Gardasil
GRN163
Herceptin
Increlex (rhIGF-1)
Lidoerm
(Lidocaine)
Liraglutide
Remicade
yrica (pregabalin)
Rozerem
Sorafenib
Sutent
Tamsulosin
Torcetrapib
Zometa
OLD DRUGS
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DRUG NOTES
[CONSTRUCT]
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Terminologies
FDA ALERTS
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Market
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levothyroxine
Protein Drug 1
Protein Drug2
Double-blind
Study
INDUSTRY
Foundamental
Science
Colloidal
Stabilization
Drug Product
Development
Patent Application
Product
Development
Product
Ingredients
Colorant
Scale up a batch 1
Drug Delivery
Industry
Drug Delivery -
Smart Bomb
Lotion, Cream,
Preps
Enteric
Coating-Eudragit
Enteric
Coating-Nutrateric
SR
Coating-Aquacoat
Drug Industry
Drug
Competitions
Drug in
Development
Cholesterol-loweri
ng
Drug-Terminologi
es
Packaging
Materials
Market
Drug Dev- 2004
Drug Dev -
2005Q1
Drug Dev- 2005Q2
Drug
Dev-2005Summer
Drug Dev-2005Q3
Orphan Drug
Protein Drug
Niche Market
Novo Norkdisk
R&D
Equipment
Blenders
CONTRACT
MANUFACT.
Nutrition
Supplements
NEW DRUGS
Arranon
Actoplus Met
Alfuzosin
Ambien CR
Avastin
Asmanex(R)
Erbitux
(cetuximab)
Gardasil
GRN163
Herceptin
Increlex (rhIGF-1)
Lidoerm
(Lidocaine)
Liraglutide
Remicade
yrica (pregabalin)
Rozerem
Sorafenib
Sutent
Tamsulosin
Torcetrapib
Zometa
OLD DRUGS
Lithium Carbonate
DRUG NOTES
[CONSTRUCT]
Clinical Research
Terminologies
FDA ALERTS
Protein Drug
Market
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levothyroxine
Protein Drug 1
Protein Drug2
Double-blind
Study
| The Food and Drug Administration approved Remicade (infliximab) to treat children with active Crohn's disease, a chronic, inflammatory condition of the bowel that can be severely debilitating. Remicade is a genetically engineered monoclonal antibody, which reduces inflammation (swelling/redness) by blocking the action of tumor necrosis factor-alpha (TNF-alpha), that was initially approved in 1998 to treat Crohn's disease in adults. |
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