Yourlawyer.com (Remicade News)

FDA Releases More Humira, Enbrel, Remicade Info

Tue, 01 Sep 2009 00:00:00 -0700

Federal regulators have released more information regarding cancers associated with drugs like Humira, Enbrel, and Remicade. Last month, the Food & Drug Administration (FDA) had mandated that the Black Box Warnings on these drugs - known as TNF blockers - highlight their possible association with lymphoma and other cancers in children and teens.

In a supplementary "Question and Answer" document released yesterday, the FDA provided more information on the types of cancers seen in children and teens treated with TNF blockers. According to the document, the following types of pediatric malignancies were reported between 2001 and 2008:

Hepatosplenic T-cell lymphoma, 10 cases
Non-Hodgkin’s lymphoma, 7 cases
Hodgkin's lymphoma, 6 cases
Leukemia, 6 cases
Malignant Melanoma, 3 cases
Thyroid cancer, 3 cases
Basal cell carcinoma, 1 case
Lymphoma and AML, 1 case
Leiomyosarcoma, 1 case
Nephroblastoma, 1 case
Renal cell carcinoma, 1 case
Metastatic hepatocellular cancer, 1 case
Malignant mastocytosis, 1 case
Neuroblastoma, 1 case
Colorectal cancer, 1 case
Yolk sac tumor, 1 case
Myelodysplasia, 1 case
Bladder cancer, 1 case

These 48 cases of pediatric cancers included both U.S. (32) and non-U.S. (16) cases. According to the document, 31 cases of malignancy were reported in children taking Remicade, including 10 cases of hepatosplenic T-cell lymphoma in patients with inflammatory bowel disorder; 15 cases of malignancy in children receiving Enbrel were reported; and two cases of malignancy in children receiving Humira were reported. The FDA also said that the 48 cases of pediatric cancers did not confirm a dose association with malignancy.

Last month, the FDA had said that there were 11 deaths among the 48 cases of cancer. The causes of death included hepatosplenic T-cell lymphoma (9 cases) and T-cell lymphoma (1 case). In the remaining case, the patient died from sepsis after achieving remission of the lymphoma.

In children, TNF blockers are used to treat rheumatoid arthritis, inflammatory bowel disorder and Crohn’s disease. They are also approved to treat a variety of chronic, inflammatory and autoimmune system diseases including juvenile idiopathic arthritis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. TNF blockers work by neutralizing a protein that, when overproduced, causes inflammation and damage to bones, cartilage and other tissue.

The FDA had been studying the link between the pediatric uses of TNF blockers and cancer since 2008.

Simponi Carries Risk of Possibly Fatal Fungal Infections

Fri, 29 May 2009 00:00:00 -0700

Simponi, a new rheumatoid arthritis drug, can cause severe and potentially fatal fungal infections, according to a new warning released yesterday by the Food & Drug Administration (FDA). Because of this risk, the agency said that when making a decision to use Simponi, doctors must balance the potential benefits with the potential risks of therapy based upon a patient’s individual need.

Simponi is one of a class of drugs known as TNF-alpha blockers. Such medications work by suppressing the immune system. Other drugs in this class include Humira, Cimzia, Enbrel, and Remicade. Simponi was only approved in April as a treatment of adult patients with: moderate to severe rheumatoid arthritis in combination with methotrexate, psoriatic arthritis (either alone or in combination with methotrexate), and ankylosing spondylitis.

It has long been known that people taking TNF-alpha blockers run a risk of developing opportunistic infections, including histoplasmosis, an infection caused by the fungus Histoplasma capsulatum. The FDA also has received reports of cases of coccidioidomycosis and blastomycosis, including deaths, in patients treated with TNF-alpha blockers. Last fall the FDA ordered the makers of TNF-alpha blockers to strengthen the existing warnings about opportunistic fungal infections linked to the drugs.

A "Dear Healthcare Professional" letter issued by Centocor Ortho Biotech, Inc. advises doctors to carefully review Simponi's prescribing information, which includes important information about the risk of serious infections including TB and invasive fungal infections, such as histoplasmosis, in a Boxed Warning.

The letter also warns that invasive fungal infections are not consistently recognized in patients taking TNF-alpha blockers. This has resulted in delays in appropriate antifungal treatment, sometimes even resulting in death. For patients who reside or travel in regions where mycoses are endemic (eg, Ohio and Mississippi River valleys and southwestern United States), invasive fungal infection should be suspected if they develop a serious systemic illness, the letter warns.

The letter also advises that patients be encouraged to report signs of infection and be closely monitored during and after treatment with Simponi and other TNF-alpha blockers for the development of invasive fungal infection. Signs and symptoms of such disorders include fever, malaise, weight loss, sweats, cough and dyspnea, pulmonary infiltrates on X-ray or serious systemic illness. TNF-alpha blockers should be discontinued in patients who develop such symptoms, and they should undergo a complete diagnostic workup. Once the infection has cleared, use of Simponi and other TNF-alpha blockers may be restarted based on a reevaluation of risks and benefits.

Humira, Kineret, Remicade May Raise the Risk of Developing Shingles

Wed, 18 Feb 2009 00:00:00 -0800

Shingles seems to be one of the adverse reactions to rheumatoid arthritis sufferers taking Humira, Kineret, and Remicade. WebMD Health News reported that these drugs, in the TNF-alpha blocker class, nearly doubled the risk of shingles—herpes zoster—in a German study involving 5,040 patient participants.

Humira, Kineret, and Remicade each increased the risk of developing shingles by 80 percent according to Anja Strangfeld, MD from the German Rheumatism Research Center in Berlin, "We compared these different types of TNF inhibitor with conventional disease-modifying anti-rheumatic drugs and we found there is an increased risk of herpes zoster in patients treated with the monoclonal antibodies." The drugs are also used in the treatment of ankylosing spondylitis, psoriatic arthritis, and Crohn’s disease because they quiet unmanageable immune responses common with these diseases, said Web MD.

The Guardian explained that rheumatoid arthritis occurs when the body’s immune system attacks joint linings, causing stiffness, swelling, and pain. Shingles occurs when the herpes zoster virus—the virus that causes chickenpox—is activated in people who have already suffered from chickenpox. Shingles cause severely painful blisters, headache, flu-like symptoms without fever, itching, tingling, pain, dizziness, weakness, vision changes, and changes in thought processes

Unfortunately, said Richard J. Whitley, MD, professor of pediatrics, microbiology, medicine, and neurosurgery at the University of Alabama, Birmingham, the drugs can not only prompt shingles in patients taking Humira, Kineret, and Remicade, the risk increases in those patients who have already suffered from shingles, reported Web MD. "It's pretty clear that if you have had previous zoster and take these anti-TNF monoclonal antibodies, you are going to reactivate it," Whitley told WebMD.

About one in five—or 25 percent—of the participants who developed shingles also suffered complications, which was more than expected, said Robert F. Betts, MD, professor of medicine at the University of Rochester, New York, according to WebMD. The risk of shingles appeared to be highest in older patients and those also taking steroids, said HealthDay News. And while a vaccine for shingles exists, it cannot be administered when anti-TNF drugs—which are immune system suppressants—are being taken as the shingles medication contains a live virus.

HealthDay News reported that severe cases of shingles—a viral infection—have been reported in patients being treated with TNF blockers and that there is an established link between the medications and fungal and bacterial infections. As a matter-of-fact, late last year, the U.S. Food and Drug Administration (FDA), urged the makers of Humira, Cimzia, Enbrel, and Remicade to increase safety warnings regarding the risk of developing opportunistic fungal infections; all of the medications carried black-box warnings concerning other safety issues, said HealthDay News.

The study was conducted at the German Rheumatism Research Centre in Berlin, Germany and its findings appear in today’s issue of the Journal of the American Medical Association, said the Guardian.

Humira, Cimzia, Enbrel and Remicade to Bear Stronger Infection Warnings

Thu, 04 Sep 2008 00:00:00 -0700

Federal regulators have ordered the makers of Humira, Cimzia, Enbrel, and Remicade to strengthen the existing warnings about opportunistic fungal infections linked to the drugs. At least 45 people are known to have died from such infections. The Food & Drug Administration (FDA) ordered the new labeling under authority it was granted with the passage of the Food and Drug Administration Amendments Act of 2007.

Humira, Cimzia, Enbrel and Remicade are known as tumor necrosis factor (TNF) blockers. They are used to treat rheumatoid arthritis, Crohn's disease and other conditions. The drugs work by suppressing the immune system. It has long been known that people taking TNF blockers run a risk of developing opportunistic infections, and the prescribing information for the drugs has included this information. But now the FDA says that current warnings are inadequate.

The FDA's order came after the agency reviewed 240 reports of histoplasmosis, an infection caused by the fungusHistoplasma capsulatum, in patients being treated with Enbrel, Humira, or Remicade. The majority of the reports involved people in the Ohio River and Mississippi River valleys (the fungus is commonly found in those areas). In at least 21 of the reports, histoplasmosis was initially not recognized by health care professionals, and antifungal treatment was delayed. Twelve of those patients died.

The FDA reviewed one reported case of histoplasmosis in a patient taking Cimzia. The FDA also has received reports of cases of coccidioidomycosis and blastomycosis, including deaths, in patients treated with TNF blockers.

The agency has given the makers of Humira, Cimzia, Enbrel and Remicade 30 days to submit the required safety labeling changes, including strengthened warnings and revisions to the Medication Guides, or to provide a reason why they do not believe labeling changes are necessary. If they do not submit new language, or if the FDA disagrees with the new language the company proposes, the Food and Drug Administration Amendments Act of 2007 provides strict timelines for resolving the labeling changes and allows the agency to issue an order directing the labeling change as deemed appropriate to address the new safety information.

The FDA is also reviewing TNF blockers over a possible link to cancer. In June, the agency said it was investigating about 30 reports of leukemia, lymphoma and other cancers in children and young adults submitted between 1998, after the approval of the first TNF blocker, through April of this year. Approximately half of the reports were lymphomas, cancer of the immune system cells, that were both Hodgkin’s and non-Hodgkin’s based.

In April, the FDA had Amgen and Wyeth include a new black box warning on the Enbrel label stating that the drug has been associated with serious infections, including tuberculosis in some patients. The Enbrel black box warning was prompted by global studies of over 20,000 patients taking Enbrel, where tuberculosis was observed in about 200 people.

Humira, Enbrel, Remicade Being Investigated for Cancer Link

Wed, 04 Jun 2008 00:00:00 -0700

Humira and other drugs used to treat autoimmune disorders are being investigated by federal regulators amid concern that they might be linked to cancer in children and young people. The drugs are known as tumor necrosis factor (TNF) blockers, and are used to treat various forms of arthritis including juvenile idiopathic arthritis and Crohn's disease.

In addition to Humira, which is made by Abbott Laboratories, four other TNF blockers are currently on the market in the US. They are Enbrel, marketed by Wyeth and Amgen; Remicade sold by Schering-Plough; and Cimizia, made by UCB of Belgium. TNF blockers impede the action of a substance made by the body’s immune system called TNF. People with an autoimmune disease, such as rheumatoid arthritis, have too much TNF in their bodies.

The FDA said its review will focus on Humira, Enbrel and Remicade. Remicade is approved for use in children with Crohn's disease. Enbrel and Humira are approved to treat children with juvenile rheumatoid arthritis, according to the FDA. The FDA is requiring the maker of Cimzia to conduct a study to assess long-term risks of the product, including lymphoma and other cancers. This study will begin in 2009 and take about 10 years to complete. All of the labels for the drugs currently address the possible risk of cancer when taking the drug.

The FDA is investigating about 30 reports of leukemia, lymphoma and other cancers in children and young adults submitted between 1998, after the approval of the first TNF blocker, through April of this year. Approximately half of the reports were lymphomas, cancer of the immune system cells, that were both Hodgkin's and non-Hodgkin's based.

The FDA has requested that makers of TNF blockers approved for use in children and young adults supply information about all reported cases of cancer among patients in these age groups taking the drugs. The FDA has also asked health-care professionals to weigh the possible risks against the benefits when prescribing TNF blockers.

In addition to the possible cancer risk, TNF blockers have been associated with an increased risk of some infections. In May, Enbrel had its label modified to include a black box warning - the FDA's strictest safety alert - about its association with serious infections, including tuberculosis. The warning was prompted by global studies of over 20,000 patients taking Enbrel, where tuberculosis was observed in about 200 people.

$19.4M awarded in J&J drug case

Thu, 14 Dec 2006 00:00:00 -0800

Johnson & Johnson's Centocor Inc. unit hid the side effects of its Remicade drug and must pay a woman with lupus symptoms $19.4 million, a Texas jury decided Wednesday.

Patricia Hamilton, 47, began taking Remicade for her Crohn's disease in December 2001 and developed drug-induced lupus the following year, she said in her lawsuit. The drug also left her with increased risk of liver failure, said her attorney.

Hamilton sued Centocor, claiming the company failed to warn doctors of the risks of the drug. A Corpus Christi jury awarded about $3.4 million in actual damages and $16 million in punitive damages. The verdict is the first ever involving Remicade, Johnson & Johnson's second-largest drug by sales.

Health Canada Endorsed Important Safety Information on Remicade (Infliximab)

Thu, 27 Jul 2006 00:00:00 -0700

Centocor, Inc. and Schering Canada, Inc., in consultation with Health Canada, are informing health care professionals and the general public of important new safety information regarding Remicade (infliximab).

Remicade (infliximab) is a chimeric IgG monoclonal antibody known as a biological response modifier that is directed against the cytokine tumour necrosis factor-alpha (TNFalpha). It is indicated for the treatment of adults with rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriatic arthritis, and chronic plaque psoriasis.

New Safety Information

Remicade is not authorized for pediatric use in Canada.
Six (6) post-marketing cases of a rare type of lymphoma called hepatosplenic T-cell lymphoma (HSTCL) have been reported in pediatric and young adult patients taking Remicade for Crohn's disease.
Exposure to Remicade® ranged from 1 or 2 infusions to over 4 years of maintenance therapy, and five of the six cases resulted in death.
All cases reported concomitant or past use of other immunosuppressive agents, including azathioprine or 6-mercaptopurine. As a result, a causal relationship between Remicade and the development of HSTCL has not been clearly established.

The six reports of HSTCL in Crohn's disease patients documented ages ranging from 12 to 31 years, with five of the cases occurring in patients aged 12 to 19. Four of the six cases occurred in males. All reports originated from the United States, and one report was recently published in the literature.1

This disease is a very rare form of non-Hodgkin's lymphoma (NHL), which occurs most commonly in adolescent and young adult males, and there are only 150 cases published in the medical literature worldwide since the disease was first described in 1990.2 The disease usually presents as marked hepatosplenomegaly with bone marrow involvement and cytopenia, most commonly thrombocytopenia. Patients may have symptoms characteristic of B-cell lymphomas with fever, weight loss, and night sweats, but without lymphadenopathy or significant peripheral blood lymphocytosis. The clinical course of the disease is extremely aggressive, with a fatal outcome in most patients within 2 years of diagnosis.

Both azathioprine and 6-mercaptopurine are known mutagens, and azathioprine has been classified as a human carcinogen.3 There have also been three reports in the literature of HSTCL occurring in Crohn's disease patients receiving these drugs without Remicade. Because all cases described concomitant or past use of such agents, a causal association between Remicade® and HSTCL has not been clearly established. However, a role for Remicade in causing or exacerbating this disease cannot be excluded.

In Canada, approximately 38,000 patients have received Remicade since its launch in 2001, with 16,000 patients having received the product for Crohn's disease. Although lymphomas have been reported in Canada in patients receiving Remicade® for Crohn's disease and other indications, there have been no reports of HSTCL.

Information regarding the risk of lymphoma in patients receiving Remicade was also previously communicated to Canadian healthcare professionals in 2004.

Remicade is only authorized in Canada for the treatment of adult patients. The Canadian Product Monograph for Remicade® is being revised to include the above updated safety information.

Cancer Risks Detailed for Arthritis Drugs

Wed, 17 May 2006 00:00:00 -0700

Rheumatoid arthritis patients taking Humira or Remicade face triple the risk of developing several kinds of cancer and double the risk of getting serious infections, a study led by the Mayo Clinic found.

The analysis builds on previous reports about the risks associated with Abbott Laboratories' Humira and Centocor's Remicade. But the earlier research focused mostly on one kind of cancer, lymphoma and infections such as tuberculosis and pneumonia.

The new study found an apparent link to other cancers, too, including skin, gastrointestinal, breast and lung tumors. It also quantifies the risks and says high doses appear to be the riskiest.

While the drugs' packaging information mentions some of the risks, the manufacturers said the new study does not prove that the medication is at fault, and they said the research was flawed.

Study co-author Dr. Eric Matteson, a Mayo Clinic rheumatologist, stressed the overall chances of developing cancer while using these drugs is still small. The researchers also noted that the medications' benefits include improving flexibility and range of movement, easing pain and increasing life expectancy, which arthritis can shorten.

In addition, the researchers noted that the risks for individual patients probably vary widely. Older, sicker people who have taken the drugs for several years probably face the highest risks, they said.

Still, the researchers said patients should be made aware of the dangers and told to seek medical help if they develop fevers, coughs or other symptoms of infection. They should also be sure to undergo the cancer screenings recommended for the general public, the researchers said.

Their study appears in Wednesday's Journal of the American Medical Association.

Matteson is working with Centocor in developing a new drug that works similarly, and he and co-author Dr. Tim Bongartz have been paid consultants to Abbott for unrelated work, but neither company funded the study. The Mayo Foundation sponsored the research.

Rheumatoid arthritis affects more than 2 million Americans, and involves a malfunctioning immune system that attacks joints throughout the body, causing pain, deformities and disability.

Dr. John Klippel, president of the Arthritis Foundation, said the study will probably not change doctors' minds, because scores of patients have benefited from the drugs. Remicade was approved in 1998, Humira in 2002.

More than a half-million patients have been treated with the two injectable drugs and a third similar medication, Enbrel, all of which block production of a protein linked with inflammation.

Enbrel was not included in the study because it differs at the molecular level, Matteson said. He said he is getting paid by Enbrel marketers Wyeth and Amgen to do a similar analysis on Enbrel alone.

Matteson's ties to Centocor and his work on Enbrel were among several omissions and errors included in disclosure statements that accompanied the study in JAMA.

He said the omissions were "errors of oversight on my part" and that he was not attempting to conceal anything. Matteson said he brought the issues to JAMA's attention on Friday.

But in an unusual move, journal editors posted a correction Tuesday on JAMA's Web site revealing that they have asked the Mayo Clinic College of Medicine to investigate.

The editors cited "the nature and extensiveness of this incorrect and incomplete reporting."

In a telphone interview Tuesday, Dr. Phil Fontanarosa, JAMA's executive deputy editor, said that "journals are not in a position to conduct full-scale, intense investigations when there are concerns. We ask the institutions to help us in getting to the bottom of these sorts of issues."

The researchers analyzed data from nine studies comparing Humira or Remicade with placebos and pooled the results. There were 29 cancers in 3,493 patients who received at least one dose of either drug, compared with three cancers in 1,512 patients on placebos.

Serious infections occurred in 126 patients on drugs and 26 on placebos. They included pneumonia and cellulitis.

An Abbott spokesperson said the analysis "doesn't reflect all the data" on Humira and said the studies were too short to sufficiently monitor cancer incidence.

Tom Schaible, Centocor vice president of medical affairs, said most of the analyzed studies used higher-than-recommended Remicade doses. "There's clearly a favorable benefits-risks ratio" with recommended doses, Schaible said.

Study: Rheumatoid-arthritis drugs may raise cancer, infection risk

Wed, 17 May 2006 00:00:00 -0700

Some drugs used to treat rheumatoid arthritis, a devastating disease that can deform bone and cause extreme pain, may increase the risk for serious infections and also some cancers in rare cases, according to an analysis of nine studies involving the drugs.

But doctors familiar with the research say the benefits of the drugs, Humira and Remicade, outweigh the risks for most people with rheumatoid arthritis.

The best course of action, they say, is for doctors to monitor their patients closely for symptoms of infection or cancer. Enbrel, a similar drug, was not included in the analysis, but a separate study is planned.

Rheumatoid arthritis affects more than 2 million Americans. It occurs when the body's immune system malfunctions and attacks joints anywhere in the body. It is a different disease from osteoarthritis, which affects 21 million Americans and begins with the breakdown of joint cartilage, causing pain and stiffness.

More than a half-million rheumatoid-arthritis patients have received therapy with the drugs so-called TNF-blocking antibodies -- which can halt the body's production of a protein that can cause inflammation. The drugs can improve range of movement, ease pain, and may increase life expectancy.

Dr. Eric Matteson, a Mayo Clinic rheumatologist who worked on the analysis published in today's Journal of the American Medical Association, said that as the drugs slow the progression of rheumatoid arthritis, they also can interfere with normal immune function.

Of 3,493 patients in the nine clinical trials who received at least one drug treatment, 29 developed cancers, compared with only three cancers in 1,512 patients who took a placebo. Serious infections, such as pneumonia, occurred in 126 patients on the drugs, compared with 26 infections in people who took placebos.

"Most of the patients appropriate for this therapy do not have other good options," Matteson said. "TNF-blocking antibodies are absolutely the best drug for many patients."

America's Top-Selling Prescription Drugs – a Who's Who of Blockbusters

Sat, 04 Mar 2006 00:00:00 -0800

According to a recent article in Forbes.com (2/27/06) that was based on figures obtained from IMS Health, a healthcare information company, the top 20 prescription drugs in the U.S. in 2005, with combined sales of $64.6 billion, were as follow:

1.    LIPITOR – Pfizer – Treats high cholesterol: $8.4 billion

2.    ZOCOR – Merck –Treats high cholesterol: $4.4 billion

3.    NEXIUM – AstraZeneca – Treats heartburn: $4.4 billion

4.    PREVACID – Abbott & Takeda – Treats heartburn: $3.8 billion

5.    ADVAIR DISKUS – GlaxoSmithKline – Treats asthma: $3.6 billion

6.    PLAVIX – Bristol-Meyers Squibb & Sanofi-Aventis – Treats heart disease $3.5 billion

7.    ZOLOFT – Pfizer – Treats depression: $3.1 billion

8.    EPOGEN – Amgen – Treats anemia: $3.0 billion

9.    PROCRIT – Johnson & Johnson – Treats anemia: $3.0 billion

10.    ARANESP – Amgen – Treats anemia: $2.8 billion

11.    ENBREL – Amgen & Wyeth – Treats rheumatoid arthritis: $2.7 billion

12.    NORVASC – Pfizer – Treats high blood pressure: $2.6 billion

13.    SEROQUEL – AstraZeneca – Treats schizophrenia: $2.6 billion

14.    EFFEXOR XR – Wyeth – Treats depression: $2.6 billion

15.    ZYPREXA – Eli Lilly – Treats: schizophrenia: $2.5 billion

16.    SINGULAIR – Merck – Treats asthma and allergies: $2.5 billion

17.    PROTONIX – Wyeth – Treats heartburn: $2.4 billion

18.    RISPERDAL – Johnson & Johnson – Treats schizophrenia: $2.3 billion

19.    NEULASTA – Amgen – Treats chemotherapy side effects: $2.2 billion

20.    REMICADE – Johnson & Johnson – Treats rheumatoid arthritis: $2.2 billion

FDA MedWatch: Remicade (infliximab) and Severe Hepatic Reactions Reported in Postmarketing Data

Wed, 22 Dec 2004 00:00:00 -0800

The FDA and Centocor notified healthcare professionals of revisions to the WARNINGS, ADVERSE REACTIONS sections and PATIENT PACKAGE INSERT of the prescribing information for Remicade, indicated for the treatment of rheumatoid arthritis, Crohn's disease and ankylosing spondylitis. Severe hepatic reactions, including acute liver failure, jaundice, hepatitis and cholestasis, have been reported in postmarketing data in patients receiving Remicade. Autoimmune hepatitis has been diagnosed in some of these cases. Severe hepatic reactions occurred between two weeks to more than a year after initiation of Remicade. Some of these cases were fatal or necessitated liver transplantation.

The "Dear Healthcare Professional" letter is below. The revised label is attached:

December 2004

IMPORTANT DRUG WARNING

Dear Healthcare Professional:

Centocor would like to inform you of important updates to the prescribing information for REMICADE (infliximab), including the addition of a Warning on hepatotoxicity and an update to the existing Warning on Risk of Infections. REMICADE is a biological therapeutic product indicated for the treatment of rheumatoid arthritis, Crohns disease and, most recently, ankylosing spondylitis.

In postmarketing experience worldwide, severe hepatic reactions including acute liver failure, jaundice/cholestasis, and hepatitis, including autoimmune hepatitis, have been rarely reported in patients receiving REMICADE. Since August 24, 1998, when REMICADE was approved in the US, approximately 576,000 patients have been treated with REMICADE worldwide. Approximately 3 patients in controlled clinical trials and 35 patients in the voluntary postmarketing reported events are considered to be severe hepatic reactions. A causal relationship between REMICADE and these events has not been established.

Centocor has added a Warning on Hepatotoxicity to the labeling for the product as follows:

WARNINGS: Hepatotoxicity

Severe hepatic reactions, including acute liver failure, jaundice, hepatitis and cholestasis, have been reported rarely in postmarketing data in patients receiving REMICADE. Autoimmune hepatitis has been diagnosed in some of these cases. Severe hepatic reactions occurred between two weeks to more than a year after initiation of REMICADE; elevations in hepatic aminotransferase levels were not noted prior to discovery of the liver injury in many of these cases. Some of these cases were fatal or necessitated liver transplantation.

Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (e.g., ?5 times the upper limit of normal) develops, REMICADE should be discontinued, and a thorough investigation of the abnormality should be undertaken. As with other immunosuppressive drugs, use of REMICADE has been associated with reactivation of hepatitis B in patients who are chronic carriers of this virus (i.e.,surface antigen positive). Chronic carriers of hepatitis B should be appropriately evaluated and monitored prior to the initiation of and during treatment with REMICADE. In clinical trials, mild or moderate elevations of ALT and AST have been observed in patients receiving REMICADE without progression to severe hepatic injury (see ADVERSE REACTIONS, Hepatotoxicity).

The Adverse Reactions section and Patient Information Sheet were also updated to include important information regarding hepatotoxicity (see enclosed prescribing information).

In addition, Centocor has added pneumonia to the existing Warnings on Risk of Infections based on clinical trial data in RA patients described in the Adverse Reactions section of the labeling.

Enclosed please find the updated prescribing information as well as the patient information sheet.

Centocor is committed to ensuring that REMICADE is used safely and effectively and is committed to providing you with the most current product information for REMICADE. You can assist us with monitoring the safety of REMICADE by reporting adverse events to Centocor at 1-800-457-6399. Alternatively, this information may be reported to FDAs MedWatch reporting system by phone (1-800-FDA-1088), facsimile (1-800-FDA-0178), the MedWatch website at www.fda.gov/medwatch, or mailed to MedWatch, HF-2, 5600 Fishers Lane, Rockville, MD 20852-9787. Both healthcare professionals and consumers should use Form 3500 for reporting adverse events.

Should you have any questions or require further information regarding the use of REMICADE, please contact Centocors Medical Affairs Department at 1-800-457-6399.

Sincerely,

Daniel E. Everitt, M.D.

Vice President,

Clinical Pharmacology and Global Pharmacovigilance

Centocor, Inc.

Johnson & Johnson Adds Warnings To Remicade Drug Label

Mon, 20 Dec 2004 00:00:00 -0800

Johnson & Johnson (JNJ) warned that patients taking Remicade may face an increased risk of liver failure and pneumonia.

The company also said the Food and Drug Administration has approved Remicade for use in patients suffering from ankylosing spondylitis, a type of arthritis of the spine.

Remicade was previously approved to treat Crohn's disease and rheumatoid arthritis in combination with another drug.

Centocor, the J&J unit that makes Remicade, said the drug has been linked to 38 cases of liver toxicity, including liver failure out of 576,000 patients who have used Remicade. However, the company said it has not been determined if Remicade actually caused liver damage.

The drug's label will be changed to warn of a possible increased risk of liver damage and to warn of an increased risk of developing pneumonia. The label had already warned of an increased risk of developing upper respiratory infections. Remicade suppress people's immune systems making them more vulnerable to infections.

Remicade was first approved by the FDA in 1998. It blocks production a protein in the body known as tumor necrosis factor, or TNF. Too much TNF is believed to play a role in Crohn's disease, an inflammation of the digestive track and rheumatoid arthritis (RA), or inflamed joints.

J&J said it will send out letters Tuesday to doctors warning them of the new side effects for Remicade. In October, the warning label was updated to warn of an increased risk of developing lymphoma, a type of cancer. Remicade is administered through a two-hour infusion in a clinic about every eight weeks to treat Crohn's and RA.

The company said the FDA based its approval for ankylosing spondylitis primarily on a clinical trial involving 279 patients treated over a 24-week period. About 60% of those receiving Remicade experienced a 20% or greater improvement in their symptoms, including a reduction in pain and increased spinal function.

Last week, J&J announced that the FDA has accepted an application for Remicade to be considered to treatment for ulcerative colitis, another digestive track condition. The FDA is reviewing the application over a six-month, fast-track period rather than the usual 10-month period.

Malvern Drug Maker Warns Of Heightened Lymphoma Risk With Remicade

Fri, 08 Oct 2004 00:00:00 -0700

Centocor is warning doctors that patients taking Remicade for rheumatoid arthritis suffered a type of cancer, lymphoma, at three times the rate of the general public.

Centocor, a subsidiary of Johnson and Johnson, is the manufacturer of Remicade. The company says the lymphoma incidence rate was six times higher among all patients who took the drug in completed clinical trials.

Experts say such toxic outcomes, however, are still rare, and that the new drugs, on balance, work markedly better than older medications, without such side effects as nausea and fatigue.

The Malvern, Pa.-based company, working with the federal drug regulatory agency, has revised its label to reflect the lymphoma risk.

The label change is the drug's second in six weeks. In late August, Centocor warned that people taking Remicade for rheumatoid arthritis and Crohn's disease can sometimes experience fatal blood and central nervous system disorders.

At least 12 people taking Remicade in combination with other drugs died worldwide.

Centocor Warns of Remicade-Lymphoma Risk

Thu, 07 Oct 2004 00:00:00 -0700

Patients taking Remicade for rheumatoid arthritis suffered a type of cancer, lymphoma, at three times the rate of the general public, manufacturer Centocor warned doctors on Thursday.

Centocor, a subsidiary of Johnson & Johnson, said the lymphoma incidence rate was six times higher among all patients who took the monoclonal antibody in completed clinical trials.

Experts said such toxic outcomes, however, are still rare, and that the new drugs, on balance, work markedly better than older medications, without such side effects as nausea and fatigue.

The Malvern, Pa.-based company, working with the federal drug regulatory agency, revised its label to reflect the lymphoma risk. According to NDCHealth, Remicade was the 28th top selling drug in 2003, with $1.5 billion in U.S. sales.

The label change is the drug's second in six weeks. In late August, Centocor warned that people taking Remicade for rheumatoid arthritis and Crohn's disease can sometimes experience fatal blood and central nervous system disorders. At least 12 people taking Remicade in combination with other drugs died worldwide.

The Food and Drug Administration said then that those deaths could not be linked definitively to Remicade use.

The company's new warning letter to doctors, released Thursday, said patients receiving Remicade suffered higher rates of lymphoma than seen in the general population. Lymphoma is cancer of the cells of the lymphatic system, tissues and organs involved in fighting infection.

Centocor said the label change is in line with warnings recently added to others drugs, such as Enbrel and Humira, in the new class that block overproduction of TNF, an inflammation-regulating protein thought to lie at the heart of rheumatoid arthritis and other autoimmune disorders.

Rheumatoid arthritis is a disease in which the body's immune system rebels, treating its own tissues as enemies to attack. Some 2.1 million Americans suffer from this illness, which ultimately deteriorates cartilage and destroys joints.

Centocor found that three people developed lymphoma among 2,410 patients taking Remicade to treat Crohn's disease or rheumatoid arthritis. That was six times higher than the lymphoma rate among healthy individuals.

But such autoimmune diseases up the odds of suffering lymphoma, making it difficult to determine whether to blame the drugs or the underlying disease.

"That's the issue here," said Dr. Tom Schaible, Centocor vice president of medical affairs. "There's not enough signal coming out of the population of patients receiving TNF blockers to distinguish it from what the underlying risk is in those diseases."

By neutralizing the overproduced protein, the new class of biologically engineered drugs relieves painful symptoms.

But an FDA advisory panel last year debated whether Amgen and Wyeth's Enbrel, Abbott Laboratories' Humira and Centocor's Remicade were also linked to 170 cases of lymphoma reported among the drugs' recipients since 1998.

"The drugs that we use are powerful because they do affect the immune system. And that's how they work in arthritis," said Steven Abramson, who was acting chairman during that March 2003 advisory committee session that scrutinized the increase in adverse events, including lymphoma.

"The good news is that you don't feel rotten taking the drug every day," said Abramson, chairman of rheumatology at New York University Hospital for Joint Diseases.

Last week, the agency approved using a combination of Remicade and methotrexate as a first-line treatment for patients with rheumatoid arthritis.

Phase three clinical trials indicated one in three patients taking the drug showed marked improvement in their psoriatic arthritis. Later this year, the company will ask the FDA to expand the drug's usage.

FDA Says Remicade Users Suffer Ailments

Tue, 24 Aug 2004 00:00:00 -0700

The Food and Drug Administration and manufacturer Centocor are warning doctors that patients receiving the drug Remicade to treat rheumatoid arthritis and Crohn's disease have suffered sometimes fatal blood and central nervous system disorders.

Centocor, a subsidiary of health care product manufacturer Johnson & Johnson, said the FDA has been told of 580 adverse reaction reports among 509,000 worldwide patients, said Craig Buchholz, a Centocor spokesman. Forty-four reports were most worrisome because they involved significant blood disorders.

At least 12 patients taking Remicade in combination with other drugs died worldwide.

"It was unclear whether these deaths were caused by this product," said Lenore Gelb, an FDA spokeswoman.

The Malvern, Pa.-based company, working with the federal drug regulatory agency, revised its label for the monoclonal antibody.

The company's Aug. 11 warning letter to doctors said patients receiving Remicade suffered reductions in their red and white blood cell, granulocyte and platelet counts, leaving them more vulnerable to abnormal bleeding and infections. In rare instances, patients suffered central nervous system disorders, including confusing immune system responses that swelled, then decayed, blood vessels.

Centocor warned physicians to exercise caution when treating patients with histories of significant blood abnormalities with Remicade. Patients with persistent fevers should seek immediate medical attention.

The Dark Side of an Arthritis Breakthrough

Wed, 30 Aug 2000 00:00:00 -0700

With her quick laugh and endless charm, it's easy to forget just how lousy Caryn Goldstein can feel. At 33, she suffers from both rheumatoid arthritis and Crohn's disease, two inflammatory conditions that leave her achy and exhausted.

"I've tried just about every drug," she says, adding that nothing has given her much relief.

She had high hopes that Remicade (generic name infliximab) would be different. The new drug, which blocks a pain-causing nuisance known as tumor necrosis factor (TNF), has proven beneficial for both Crohn's and rheumatoid arthritis. A perfect fit. But for Goldstein, the drug backfired.

The series of shots left her disoriented, and for a week afterward she felt like she had a terrible case of the flu. Then at a hospital last October in Kentucky, she looked up from the needle in her arm to see her nurse's eyes turn "as wide as saucers."

A bright rash had spread almost instantly across Goldstein's face. Fearing that Remicade could put her at risk for deadly anaphylactic shock, she and her doctor decided that was enough.

"Remicade was a disaster for me," says Goldstein.

Many patients have experienced quite the opposite. Indeed, Remicade and other drugs that interfere with TNF are some of the most impressive pain-relief missionaries to come around in years, often providing help to those who have exhausted all other options.

"These drugs are the miracle drugs of the decade," says John Cush, MD, an arthritis specialist at Presbyterian Hospital in Dallas. "The effects can be just dramatic."

But doctors are noticing a dark side as well. Although problems are rare, anti-TNF drugs are increasingly linked to unusual and distressing side effects. On August 17th, the Food and Drug Administration (FDA) will meet with their arthritis advisory board to discuss the latest concerns.

"I have no idea how this will shake out," says one former FDA board member.

Adverse events reports filed with the FDA put these drugs in the vicinity of a number of serious and potentially deadly side effects. The reports, which were made available to Medscape Health through a Freedom of Information Act request, are hopelessly incomplete. They do not, for example, place blame on a specific drug: Rather, they simply show that a drug was taken around the time of a severe reaction.

Nevertheless, the FDA relies on these documents to issue new warnings, or worse--to determine if a drug is dangerous enough to be withdrawn. Some adverse events found over a 2-month period:

From September 1 to December 31st of 2000, 22 patients died while taking Enbrel (etanercept) and 18 needed emergency care at a hospital. Remicade, which has greater sales overall, was listed in 48 deaths and nearly 100 life-saving interventions to prevent "permanent damage." Many patients were taking various drugs in addition to anti-TNF ones. But the only treatment listed for one 9-year-old girl who needed to be hospitalized was Enbrel. The drug is approved for use in juvenile rheumatoid arthritis.

At least five patients developed lupus after taking Remicade, including one 43-year-old man. Although there is no conclusive evidence that these drugs cause lupus, experts say that laboratory experiments suggest a possible link. At a recent medical conference in the Czech Republic, French researchers announced that two of their patients developed lupus soon after starting Enbrel.

Warnings that the FDA issued earlier on anti-TNF drugs continue to show up in the latest reports, including nervous system disorders and deadly infections like sepsis. Disturbing new cases of tuberculosis show up as well. Officials say that as many as 60 patients worldwide have developed tuberculosis while taking Remicade, and nearly a dozen while taking Enbrel.

Experts familiar with these reports say that it nearly impossible to tell how dangerous Enbrel and Remicade might be. Arthritis patents are sick to begin with, and they are likely to take various immune-suppressing treatments, which could be the real trouble.

"A lot of times when you get these reports, it just has very incomplete data," says Leslie Garrison, senior vice president of clinical research for Immunex, the company that markets Enbrel. "We've been doing our homework and it appears that all these rare events are not outside the expected rates."

Long-term clinical trials show that TNF agents are overwhelmingly safe for the 5 years they have been looked at. But experts say that such studies may give an incomplete picture as well.

"You only use the most healthy patients for a study," says one researcher who took part in a TNF drug trial and asked not to be named. Stacking the deck may make it hard to tell how others will do, especially if they are elderly or suffer from other conditions besides arthritis. It's left to random adverse event reports to fill in the blanks.

"Any death is a concern," the researcher says.

And there is reason to suspect that there may be more problems than what is recorded.

"Most doctors don't report this stuff," says Cush. "It's a pain in the ass."

He estimates that the real number of adverse events related to these drugs could be ten times as high as the FDA suggests. Caryn Goldstein, for one, says authorities were not told about her bad reaction to Remicade.

"I didn't know you could do this in cases like mine," she says.

Should Enbrel and Remicade be withdrawn? Hopefully not, experts say. All drugs come with an inherent risk, and rheumatologists have toiled for years with dodgy treatments because they had little else. Anti-TNF agents offer a more precise way to attack arthritis and they show a startling potential to turn the disease around.

"These drugs are having profound effects on the joints," say Jack Klipple, the scientific advisor for the Arthritis Foundation.

Unless TNF agents are more dangerous than expected, experts urge doctors and patients to keep an open mind.

"It's really an individual decision," say Cush. "Are they willing to accept the known and unknown risks for a better quality of life?"

Remicade Lymphoma Lawyer infliximab side effects lawsuit

Wed, 30 Aug 2000 00:00:00 -0700

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Injured by Remicade?

Patients taking Remicade (Generic:Infliximab) for rheumatoid arthritis suffered a type of cancer, lymphoma, at three times the rate of the general public, manufacturer Centocor warned. Centocor, a subsidiary of Johnson & Johnson, said the lymphoma incidence rate was six times higher among all patients who took the monoclonal antibody in completed clinical trials.

Remicade is manufactured by Centocor and distributed by Johnson & Johnson and is used to treat rheumatoid arthritis and Crohn's disease. The FDA has been told of 580 adverse reaction reports among 509,000 worldwide patients, said Craig Buchholz, a Centocor spokesman. Forty-four reports were most worrisome because they involved significant blood disorders. At least 12 patients taking Remicade in combination with other drugs died worldwide.

The company's Aug. 11 warning letter to doctors said patients receiving Remicade suffered reductions in their red and white blood cell, granulocyte and platelet counts, leaving them more vulnerable to abnormal bleeding and infections. In rare instances, patients suffered central nervous system disorders, including confusing immune system responses that swelled, and then decayed, blood vessels.

Centocor warned physicians to exercise caution when treating patients with histories of significant blood abnormalities with Remicade. Patients with persistent fevers should seek immediate medical attention.

Remicade (Infliximab), an immune-suppressing drug used to treat rheumatoid arthritis and Crohn's disease, is reported to be responsible for 70 reported cases of tuberculosis (TB) among US patients. The cases, at least four of which were fatal, were reported to the Food and Drug Administration between 1998 and May of this year. Researchers who reviewed the cases say that the immune-system protein infliximab suppresses called tumor necrosis factor alpha (TNF-alpha) appears to be key in controlling TB infection.

Around 150,000 people worldwide have received Infliximab infusions since the drug's approval in 1998. Pennsylvania-based Centocor, which announced it was changing the drug's prescribing information to address the TB concerns. The revised labeling states that patients should be tested and treated for inactive, or latent, TB prior to Infliximab therapy. Latent TB refers to a chronic, but symptom less and noncontiguous, infection. Such TB infections are prevalent throughout the world because in most people, the immune system is able to suppress TB bacteria.

Up to 15 million Americans are estimated to have latent TB infections. When the immune system is suppressed as it is in patients on infliximab latent TB can become active. Active TB usually attacks the lungs, causing symptoms such as a severe cough, chest pain and weight loss. It is spread through the air from person to person.

If you or a loved one took Remicade and suffered side effects, please fill out the form at the right for a free case evaluation by a qualified drug side effects attorney.