Biological agents used to treat rheumatoid arthritis seem to be associated with an increased risk of skin cancer, indicates a systematic review of published research in the Annals of the Rheumatic Diseases.

Inflammatory arthritis has been linked to an increased risk of some cancers, such as lymphoma and lung cancer, but a lower risk of others, such as bowel and breast cancers. But it has been unclear to what extent tumour necrosis factor (TNF) inhibitors - drugs which act on the immune system - might affect risk.

TNF inhibitors include the monoclonal antibodies infliximab and adalimumab and the protein etanercept.

The researchers base their findings on 21 studies and eight conference abstracts, which met their strict inclusion criteria of reporting data on cancer associated with TNF inhibitors. In all, this provided information on more than 40,000 patients and almost 150,000 cumulative years of exposure to these drugs.

The studies were drawn from an extensive trawl of clinical research databases, and findings presented to the American College of Rheumatology, the European League against Rheumatism, and the British Society for Rheumatology between 1998 and 2010.

The pooled risk from seven studies for the development of any cancer showed that there was negligible or no increased risk, overall.

Two studies indicated that there was no evidence that patients taking TNF inhibitors over the long term were at increased risk of cancer either. And although patients who had had cancer before were more likely to be diagnosed with the disease again, this was not affected by the use of TNF inhibitors.

But four studies showed that patients treated with these drugs were 45% more likely to develop skin cancer other than melanoma, with two studies indicating that patients taking TNF inhibitors were 79% more likely to develop a melanoma than patients not taking these drugs.

"This systematic review and meta analysis provides reassurance to physicians and patients that the treatment of [rheumatoid arthritis] with TNF inhibitors does not increase the risk of malignancy, particularly lymphoma," write the authors. "However, it does appear to increase the risk of skin cancer, including melanoma," they add.

Provided by British Medical Journal (news : web)

Public release date: 7-Sep-2011
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Contact: Marla Paul
Marla-Paul@northwestern.edu
312-503-8928
Northwestern University

New 'bouncer' molecule halts rheumatoid arthritis

Protective protein prevents immune system from ravaging joints and bones

CHICAGO -- Researchers at Northwestern University Feinberg School of Medicine have discovered why the immune cells of people with rheumatoid arthritis become hyperactive and attack the joints and bones. The immune cells have lost their bouncer, the burly protein that keeps them in line the same way a bouncer in a nightclub controls rowdy patrons.

The Feinberg School team has identified this bouncer, a protein called P21, which prevents immune cells from launching into their destructive rampage through the cartilage and bone. When the scientists developed and injected an imitation of the protein into an animal model of rheumatoid arthritis, the disease process was halted.

"The bouncer molecule stopped the immune cells from going crazy," said lead author Harris Perlman, associate professor of rheumatology at Northwestern's Feinberg School. "Imagine destructive customers in a bar, and the bouncer says, 'You are going to behave!' That's P21. This discovery opens up a new avenue for future therapies, which are greatly needed for rheumatoid arthritis."

Previous research by the Feinberg team showed people with rheumatoid arthritis were low in P21, but the protein's role was unknown. The new study, which will be published in the journal Arthritis & Rheumatism, reveals the protein's vital role in keeping the immune cells in check.

Currently, there is no effective, nontoxic way to stop the hyperactive immune cells, Perlman said.

To develop the new approach, Perlman and his team tested five different parts, called peptides, of P21. He slipped each peptide into a "ghostlike" molecule that he injected into mice with a rheumatoid arthritis-like disease. The molecule secretly infiltrated the immune cells. After the seven-day trial, one of the tested peptides had calmed the overactive immune cells without toxic effects. Next, Perlman plans a 30-day study with the same peptide to monitor efficacy and toxicity over a longer period of time.

Existing treatments for rheumatoid arthritis include low-level chemotherapy and steroids. These are not always effective, however, and they are frequently accompanied by side effects. A newer class of therapy, which is sometimes used in combination with chemotherapy and steroids, is biologic response modifiers. These are antibodies or other proteins that reduce the inflammation produced by the hyperactive immune cells. These biologics don't work for everyone, though, and can be associated with side effects including the risk of infection.

One of the most famous American artists is Thomas Chambers. It's called Alligator Fisher and I'm thinking about getting because it reminds me of my cajun heritage, most of my family is from Louisiana. One of my favorites that she had was done by John Roeder. It was painted in 1988 by Reverend Howard Finster and is done in vibrant colors and also depicts the buildings in the market like an ice cream parlor and the Hotel Van Nuys. Maybe it's because I spent a lot of time playing in my tree house, that the trees in the picture appealed to me so much.There is a subcategory of folk art paintings since I was a child.My sister also shares my love for folk art. Still, they are a joy to behold. It's a beautiful painting but it's just too depressing to hang anywhere. I don't know whose smile is bigger, the one in the painting or the one on my face every time I look at it. I saw a painting he did of a fishing scene but I chose not to buy it. It's too bad my parents didn't let her play football with the boys and I used to tease her relentlessly and pull her pigtails whenever I got the chance.One of my favorite paintings was done in 1962 by Bill Dodge. When she died, she left me the painting.....

When the scientists developed and injected an imitation of the protein into an animal model of rheumatoid arthritis, the disease process was halted. But it has been unclear to what extent tumour necrosis factor (TNF) inhibitors - drugs which act on the immune system - might affect risk. "Imagine destructive customers in a bar, and the bouncer says, 'You are going to behave!' That's P21. After the seven-day trial, one of the tested peptides had calmed the overactive immune cells without toxic effects. Existing treatments for rheumatoid arthritis include low-level chemotherapy and steroids. These are antibodies or other proteins that reduce the inflammation produced by the hyperactive immune cells. "This systematic review and meta analysis provides reassurance to physicians and patients that the treatment of [rheumatoid arthritis] with TNF inhibitors does not increase the risk of malignancy, particularly lymphoma," write the authors. "However, it does appear to increase the risk of skin cancer, including melanoma," they add. The researchers base their findings on 21 studies and eight conference abstracts, which met their strict inclusion criteria of reporting data on cancer associated with TNF inhibitors. The new study, which will be published in the journal Arthritis & Rheumatism, reveals the protein's vital role in keeping the immune cells in check. The pooled risk from seven studies for the development of any cancer showed that there was negligible or no increased risk, overall. Currently, there is no effective, nontoxic way to stop the hyperactive immune cells, Perlman said.edu312-503-8928Northwestern University New 'bouncer' molecule halts rheumatoid arthritisProtective protein prevents immune system from ravaging joints and bones CHICAGO -- Researchers at Northwestern University Feinberg School of Medicine have discovered why the immune cells of people with rheumatoid arthritis become hyperactive and attack the joints and bones. Two studies indicated .There is a water scene that I really like painted in 1940.One of my favorite paintings was done in 1962 by Bill Dodge.There is a subcategory of folk art paintings that depict the world of black Americans. One of my favorites that she had was done by John Roeder. I don't particularly care for his art. I have a friend who collects these and I found one of a woman reclining in a hammock.Another painting that I admire is called Howard in 1944.The painting that has touched me the most features a sad little girl and is called A Letter From My Mother.I have loved folk art paintings since I was a child.One of the most famous American artists is Thomas Chambers. It's of a swamp house on a bayou and has a Louisiana feel to it. I spent a lot of time playing in my tree house, that the trees in the picture appealed to me so much. It is done in vibrant colors and also depicts the buildings in the market like an ice cream parlor and the Hotel Van Nuys. I don't know whose smile is bigger, the one in the painting or the one on my face every time I look at it. If she could kick the ball they way she liked to kick me in the knee, I'd see to it she played for my team every time. It's a beautiful painting but it's just too depressing to hang anywhere. It's called Alligator Fisher and I'm thinking about getting because it reminds me of my cajun heritage, most of my family is from Louisiana. Still, they are a joy to behold. It's called First Trolley to Van Nuys and shows the center of a town filled with people. She looked so

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Biological agents used to treat rheumatoid arthritis seem to be associated with an increased risk of skin cancer, indicates a systematic review of published research in the Annals of the Rheumatic Diseases.

Inflammatory arthritis has been linked to an increased risk of some cancers, such as lymphoma and lung cancer, but a lower risk of others, such as bowel and breast cancers. But it has been unclear to what extent tumour necrosis factor (TNF) inhibitors - drugs which act on the immune system - might affect risk.

TNF inhibitors include the monoclonal antibodies infliximab and adalimumab and the protein etanercept.

The researchers base their findings on 21 studies and eight conference abstracts, which met their strict inclusion criteria of reporting data on cancer associated with TNF inhibitors. In all, this provided information on more than 40,000 patients and almost 150,000 cumulative years of exposure to these drugs.

The studies were drawn from an extensive trawl of clinical research databases, and findings presented to the American College of Rheumatology, the European League against Rheumatism, and the British Society for Rheumatology between 1998 and 2010.

The pooled risk from seven studies for the development of any cancer showed that there was negligible or no increased risk, overall.

Two studies indicated that there was no evidence that patients taking TNF inhibitors over the long term were at increased risk of cancer either. And although patients who had had cancer before were more likely to be diagnosed with the disease again, this was not affected by the use of TNF inhibitors.

But four studies showed that patients treated with these drugs were 45% more likely to develop skin cancer other than melanoma, with two studies indicating that patients taking TNF inhibitors were 79% more likely to develop a melanoma than patients not taking these drugs.

"This systematic review and meta analysis provides reassurance to physicians and patients that the treatment of [rheumatoid arthritis] with TNF inhibitors does not increase the risk of malignancy, particularly lymphoma," write the authors. "However, it does appear to increase the risk of skin cancer, including melanoma," they add.

Provided by British Medical Journal (news : web)

Public release date: 7-Sep-2011
[ | E-mail | Share ]

Contact: Marla Paul
Marla-Paul@northwestern.edu
312-503-8928
Northwestern University

New 'bouncer' molecule halts rheumatoid arthritis

Protective protein prevents immune system from ravaging joints and bones

CHICAGO -- Researchers at Northwestern University Feinberg School of Medicine have discovered why the immune cells of people with rheumatoid arthritis become hyperactive and attack the joints and bones. The immune cells have lost their bouncer, the burly protein that keeps them in line the same way a bouncer in a nightclub controls rowdy patrons.

The Feinberg School team has identified this bouncer, a protein called P21, which prevents immune cells from launching into their destructive rampage through the cartilage and bone. When the scientists developed and injected an imitation of the protein into an animal model of rheumatoid arthritis, the disease process was halted.

"The bouncer molecule stopped the immune cells from going crazy," said lead author Harris Perlman, associate professor of rheumatology at Northwestern's Feinberg School. "Imagine destructive customers in a bar, and the bouncer says, 'You are going to behave!' That's P21. This discovery opens up a new avenue for future therapies, which are greatly needed for rheumatoid arthritis."

Previous research by the Feinberg team showed people with rheumatoid arthritis were low in P21, but the protein's role was unknown. The new study, which will be published in the journal Arthritis & Rheumatism, reveals the protein's vital role in keeping the immune cells in check.

Currently, there is no effective, nontoxic way to stop the hyperactive immune cells, Perlman said.

To develop the new approach, Perlman and his team tested five different parts, called peptides, of P21. He slipped each peptide into a "ghostlike" molecule that he injected into mice with a rheumatoid arthritis-like disease. The molecule secretly infiltrated the immune cells. After the seven-day trial, one of the tested peptides had calmed the overactive immune cells without toxic effects. Next, Perlman plans a 30-day study with the same peptide to monitor efficacy and toxicity over a longer period of time.

Existing treatments for rheumatoid arthritis include low-level chemotherapy and steroids. These are not always effective, however, and they are frequently accompanied by side effects. A newer class of therapy, which is sometimes used in combination with chemotherapy and steroids, is biologic response modifiers. These are antibodies or other proteins that reduce the inflammation produced by the hyperactive immune cells. These biologics don't work for everyone, though, and can be associated with side effects including the risk of infection.