News & Views Newletter
edited by Jack Nicholas, cornishpro@aol.co

PSORIATIC ARTHRITIS NEWS AND VIEWS
VOL. 2 ISSUE 23 October 31, 2002
PSORIATIC ARTHRITIS MEDICAL NEWS

ARTHRITIC JOINTS COMMON AMONG U.S. ADULTS

NEW YORK (Reuters Health) - As many as one in three US adults, or 70 million in all, have arthritis or chronic joint problems, causing disability in as many as 8 million, according to the Centers for Disease Control and Prevention (CDC).

The CDC issued a report on the prevalence of arthritis and joint problems among US adults in the October 25th issue of its Morbidity and Mortality Weekly Report.

"Arthritis is a major health problem that will likely increase as the population ages," Dr. Chad Helmick of the CDC's Arthritis Program at the National Center for Chronic Disease Prevention and Health Promotion told reporters during a telebriefing Thursday.

The updated estimates come from the 2001 Behavioral Risk Factor Surveillance System. "This article is important because it provides, for the first time, directly measured estimates of arthritis and chronic joint symptoms for people in each of the 50 states," Helmick said.

According to the data, the prevalence of arthritis and chronic joint symptoms among adults 18 and older ranges from 17.8% in Hawaii to 42.6% in West Virginia. "When you put together all the estimates from the 50 states you get a national estimate of 69.9 million," Helmick said. "This number is much larger than the number we had previously, which was 43 million."

He added, "In our minds this new national estimate of arthritis does not represent an epidemic, it really represents a better way of capturing the people who have always been out there with arthritis or chronic joint symptoms."

Confirming past research, the prevalence of arthritis and joint problems increases with age, is higher in women than men, and in non-Hispanic whites and non-Hispanic blacks than in other racial/ethnic groups. People with less education and those who are physically inactive or overweight also have a higher prevalence of arthritis.

Helmick emphasized, however, "all demographic groups are affected by arthritis and chronic joint problems. That includes children, although that was not addressed in this study, young, middle-aged and older adults, both genders and all racial groups."

Acknowledging the importance of arthritis as a growing public health problem, The Healthy People 2010 initiative, which sets health objectives for the nation, for the first time has arthritis objectives. Copyright © 2002 Reuters Limited.

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ANTI-INFLAMMATORY DRUGS TAKEN BY PATIENTS WITH ARTHRITIS MAY INCREASE BENEFIT OF ASPIRIN IN PREVENTING HEART ATTACK
(American College of Rheumatology) October 2002

Patients on low-dose aspirin therapy who had been prescribed a non-steroidal anti-inflammatory drug (NSAID) in the first year following a heart attack were less likely to suffer a recurrent acute heart attack in that year compared to those who had not been prescribed an NSAID, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in New Orleans, Louisiana.

While aspirin is known for its benefits to patients with heart problems, it is not known whether NSAIDs also provide similar benefits. Moreover, the use of both by heart patients has previously been unstudied. In this study, researchers conducted a population-based study of 28,881 patients 66 years of age or older to examine the interaction between aspirin therapy and NSAIDs (such as diclonfenac, naproxen or ibuprofen) in patients who had already had a heart attack. They found that patients on aspirin therapy who were also taking an NSAID were significantly less likely to suffer repeat heart problems. The results of this study suggest that NSAIDs may increase the amount of cardio protection afforded by aspirin therapy in patients with known heart disease. Analysis of the data is ongoing, and researchers are investigating whether results could be influenced depending upon the type of NSAID prescribed.

"Heart disease is prevalent and NSAID use is common, which means that the interaction between aspirin and NSAID use may have a large public health impact," said Marie Hudson, MD, FRCPC from McGill University, and a lead investigator in the study. "In our study population of patients with heart disease who were on aspirin therapy, the use of NSAIDs may have contributed to decreasing the risk of recurrent heart attacks. However, further analysis of the data will confirm these results and may yield insight into any differences among different kinds of NSAIDs."

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RHEUMATOID ARTHRITIS PATIENTS WITH HMO COVERAGE MAY NOT HAVE ACCESS TO NEW MEDICATIONS (American College of Rheumatology)

Health maintenance organizations strive to lower the cost of rheumatoid arthritis care by reducing the use of new medications, not by lowering the number of hospital admissions or surgeries, according to research presented at the American College of Rheumatology Annual Scientific Meeting in New Orleans, Louisiana.

Most of the studies on the impact of health maintenance organizations (HMOs) and access to quality care have been conducted on healthy populations. These studies indicate that HMOs save costs by lowering the use of hospital stays. However, studies of the impact of HMOs on people with rheumatoid arthritis do not find that HMOs lower health care use, including hospital admissions, total joint replacement surgeries or outpatient surgeries. In a study of 493 individuals, researchers analyzed whether people with rheumatoid arthritis receiving care from HMOs are less likely to use anti-TNF agents (etanercept or infliximab) or COX-2 inhibitors to treat their disease. The research shows that people with rheumatoid arthritis who participate in HMOs were significantly less likely to receive any form of anti-TNF therapy or COX-2 inhibitors.

"In recent years, several expensive new medications have been approved by the U.S. Food and Drug Administration for the care of individuals with rheumatoid arthritis. This study indicates that rheumatoid arthritis patients in HMOs are much less likely to receive these new medications. "said Edward Yelin, PhD, Professor of Medicine and Health Policy, University of California-San Francisco, and a lead investigator in the study."Since we had previously found that HMOs do not reduce the use of the hospital or surgery for such patients, controlling medications may be the way that they seek to reduce the costs of treating people with this disease."

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NEW TYPE OF DRUG BUILDS BONE --- AND MORE
By Daniel DeNoon WebMD Medical News & Reviewed By Brunilda Nazario, MD

Oct. 24, 2002 -- An estrogen-like drug reverses bone loss without estrogen's side effects. The startling discovery promises novel treatments for age-related bone loss, heart disease, and even Alzheimer's disease.

This makes Stavros Manolagas, MD, PhD, one happy scientist. His theories -- once scoffed at -- have opened the floodgates to what promises to be a stream of new drugs for a wide variety of conditions.

Manolagas is director of the Osteoporosis and Metabolic Bone Diseases Center in Little Rock, Ark., funded by the Veterans Administration and the Universi ty of Arkansas. For years, he's suggested that the sexual -- and sometimes cancer-promoting -- effects of the female sex hormone estrogen can be separated from its healthy effects on bone, heart, and brain.

"It's not just me -- lots of people for the last 40 years have talked about this, but nobody listened," Manolagas tells WebMD. "There was no evidence until we came upon these striking effects in bone cells. Even after we reported these findings last year, a lot of people weren't convinced."

The world now is taking notice. In the Oct. 25 issue of Science, Manolagas and colleagues report that a new type of drug -- dubbed estren -- rebuilds bone in mice. In fact, it worked even better than estrogen in female mice. Amazingly, it also worked in male mice. And the drug had no effect on sex organs.

"What we are trying to do is keep the beneficial effects of estrogen while eliminating the side effects," Manolagas says. "If we have the bone, heart, and brain protection of hormones without hormone side effects, we can have our cake and eat it, too. This is proof in an animal that not only do these activities exist, but that the synthetic compound can have superior biological effects to the natural hormone."

Jill Carrington, PhD, of the National Institute of Aging's biology of aging program, says the findings may one-day lead to treatments for many age-related problems.

"This really points out a new direction to follow in order to develop treatments for osteoporosis -- and it may have broader implications than that," Carrington tells WebMD. "Particularly in light of the questions now being asked about current hormone-replacement therapies, this is very important."

Silvina Levis, MD, director of the osteoporosis center at the University of Miami in Coral Gables, Fla., warns that it remains to be seen whether estren or similar compounds can become safe and effective drugs.

"This is very exciting. We just have to see if whether these findings in mice translate to human beings," Levis tells WebMD. "It is interesting, it is novel, but we are a long way from having a new treatment."

Manolagas says it will be two or three years before an estren-like drug is ready for human safety tests. A start-up firm, Anabonix, shares development rights with the University of Arkansas.

'I think this is a new area of pharmacology," Manolagas says. "We are talking about something that affects all the tissues of the body. As far as we can see these effects are happening across the board."

For example, Manolagas speculates, estren-like compounds might protect brain cells against the toxic effects of beta amyloid -- suspected to be the main culprit in Alzheimer's disease. © 2002 WebMD Inc. All rights reserved.

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NEW TARGET FOR SJOGREN SYNDROME
By Jennifer Warner WebMD Medical News & Reviewed By Michael Smith, MD

The discovery of a protein that triggers Sjögren syndrome in mice is now providing valuable clues into this immune disorder. Researchers say they've already tested a vaccine that, at least in mice, stops the body's attack on its moisture-producing glands.

The disease, known as Sjögren syndrome, most frequently strikes middle-aged or postmenopausal women and affects up to 1% of the population. It often occurs along with other diseases that affect body tissues, such as rheumatoid arthritis, lupus, and scleroderma.

The syndrome causes the body's immune system to destroy glands in the eyes, mouth, and other parts of the body that produce much-needed lubrication and moisture. Symptoms include dry eyes and mouth, fatigue, and joint pain, and there are currently no effective treatments.

In a study published in the Oct. 5 issue of the journal The Lancet, researchers say they've identified a protein, known as ICA69, that plays a vital role in the development of Sjögren syndrome. By removing the gene that produces this protein in mice, researchers were able to prevent the disease from developing in the tear glands and substantially limit the disease in the salivary glands.

In addition, the researchers say a prototype vaccine was able to stop the disease from progressing in mice that already had Sjögren syndrome.

"Our vaccine was able to stop Sjögren syndrome even after the disease had fully developed, an unusual finding, since in other autoimmune disorders it is impossible so far to stop and reverse the disease process once it is fully established," says researcher Michael Dosch, MD, senior scientist at The Hospital for Sick Children in Toronto, in a news release.

"This finding is also exciting because it opens the door to further knowledge about treating selective organ autoimmune diseases, including the possibility of vaccines," says Dosch.

Researchers say they are planning a study involving at least 100 Sjögren patients to learn more about the link between this protein and the immune system in preparation for potential clinical trials of the vaccine. © 2002 WebMD Inc. All rights reserved.

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Editors Note: The following scientific publication is from PubMed Central, a digital archive of life sciences journal literature managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM). Thanks to Megan511th.com, one of our Moderators from California, for suggesting this information. Research for this article originated in the United Kingdom.

ASSESSING PERIATICULAR BONE MINERAL DENSITY IN PATIENTS WITH EARLY PSORIATIC ARTHRITIS OR RHEUMATOID ARTHRITIS
Harrison BJ, Hutchinson CE, Adams J, Bruce IN, Herrick AL. Department of Rheumatology, North Manchester General Hospital and ARC Epidemiology Unit, University of Manchester, Manchester, UK

BACKGROUND: Periarticular osteoporosis is an early finding in the hands of patients with rheumatoid arthritis (RA), due to release of bone resorbing cytokines from the inflamed synovium. There has been disagreement as to whether periarticular bone loss occurs in psoriatic arthritis (PsA). Bone mineral density (BMD) can now be measured accurately using dual energy x ray absorptiometry (DEXA). Recently, DEXA has been used to measure periarticular BMD at predefined regions of interest (ROIs) around the joints.

OBJECTIVES: Firstly, to compare periarticular BMD around the finger joints of patients with early RA or PsA. Secondly, to determine whether periarticular bone loss is related to joint inflammation and radiological erosions in RA and PsA. METHODS: Seventeen patients with RA and 15 with PsA were recruited, all with disease duration of less than five years. All finger joints were examined by one person for swelling, or tenderness, or both. Hand radiographs were scored for the presence of erosions. Periarticular BMD was measured at 10 predetermined ROIs using a Hologic QDA-4500A fan-beam densitometer.

RESULTS: Patients with PsA were less likely to be positive for rheumatoid factor (RF) (13% v 94%) and more likely to be men (60% v 23%) than patients with RA. There were no other clinical differences between patients with RA or PsA. Patients with RA had significantly lower BMD at each of the ROIs than those with PsA (p < 0.05). However, these differences disappeared after adjusting for age and sex. Among patients with RA, those with a higher total number of swollen and/or tender hand joints had significantly lower periarticular BMD at the metocarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. No such association was found for patients with PsA.

CONCLUSIONS: In early disease, periarticular bone loss occurred both in patients with RA and those with PsA. Among patients with RA, periarticular osteoporosis was related to measures of joint inflammation. There was no association between joint inflammation and periarticular bone loss in patients with PsA, which lends support to the hypothesis that the primary site of inflammation in PsA is extrasynovial. PMID: 12379525 [PubMed - as supplied by publisher]

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HALF OF CLINICALLY DEPRESSED NOT DIAGNOSED
Oct. 2002 By Lisa Ellis - InteliHealth News Service

If you were depressed, you'd certainly know it, right? Well, maybe not.

Experts estimate that about half of the 20 million Americans who are clinically depressed, and could benefit from treatment, have not been diagnosed.

Harvard Medical School psychiatrist Douglas G. Jacobs, M.D., started National Depression Screening Day 11 years ago in an effort to find and help some of the millions of Americans who were suffering alone.

The annual program, which takes place Oct. 10, has expanded to 2,000 sites nationwide. It now screens for not only depression but also manic-depression (bipolar disorder), generalized anxiety disorder and post-traumatic stress disorder (PTSD).

Dr. Jacobs, executive director of National Depression Screening Day, urges anyone with troubling symptoms to seek screening. "People shouldn't have to say, 'Do I have depression, should I go to this screening?' If they're not feeling right, they should go."

The PTSD screening began in 2001 as a response to the Sept. 11 terrorist attacks. This year is the first year that all sites will offer it, however, says Dr. Jacobs, who is an associate clinical professor of psychiatry at Harvard.

It's not known whether more participants showed signs of mental illness last year, the first screening after the attacks, Dr. Jacobs says, because no funds have been available to analyze the numbers. National Depression Screening Day will be analyzing its data this year for such trends.

"What we know about depression is that 50 percent of cases are brought on by negative life events; 50 percent come out of the blue," he says. "Given that this year has had an inordinate number of negative events, one would intuit that there would be more cases of depression."

"The events of the past year have affected us all," Dr. Jacobs says. "It is understandable, and even normal for people to feel sad, angry, tense, or irritable; to have difficulty sleeping or nightmares, but these symptoms should resolve over time. If these symptoms persist or interfere with the person's ability to function normally, professional help should be sought."

About 80,000 to 100,000 people are screened each year, and usually the tests show that three out of four participants need a full professional evaluation, Dr. Jacobs says. Because this is a self-selected group, the percentage of illness is higher than in the general population, he says.

"Scoring positive on the test doesn't mean that you have the disorder," just that you need further evaluation, he says. "One of our strengths is that if we can get people to the screening and show them that their symptoms are consistent with a diagnosis and they should get an evaluation, 60 [percent] to 70 percent of them go."

The screening includes an educational presentation on mood and anxiety disorders, one or more questionnaires and a discussion with a mental-health professional.

Part of the message, Dr. Jacobs says, is that depression and other disorders have recognizable symptoms, and that they can be treated. "The treatments do not have to be long-term, and the earlier you get treatment the better the response."

Anyone who wants to locate a nearby screening site can call (800) 520-NDSD (6373).

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SKIN, NATURAL-ANTIBIOTICS STUDIED
October 2002 (The Associated Press)

Scientists say they have found evidence that some people are vulnerable to infections because they lack certain germ-fighting chemicals naturally present in the skin.

The chemicals themselves were discovered a few years ago, and scientists have long known that they help protect animals from infection.

In a new study, researchers offered evidence that a lack of these natural antibiotics may explain why people with the most common form of eczema are highly prone to staph infections of the skin.

The skin has long been regarded as simply a protective barrier that separates us from our environment. But more recently, scientists have come to suspect that it plays a more active role, producing its own chemical defenses against microbes.

In Thursday's issue of the New England Journal of Medicine, researchers report that eczema sufferers typically make too little of two of these germ killers.

The discovery suggests that staph infections can be fought off by replacing these chemicals or by stimulating their production.

One of the researchers, Dr. Tomas Ganz of UCLA's medical school, cautioned that more research is needed to prove beyond a doubt that a lack of these chemicals contributes to eczema victims' infections.

The study involves a type of eczema called atopic dermatitis, an itchy allergic condition that often causes scratching that leaves the skin inflamed. It affects about 15 million people in the United States. About 90 percent of them wind up with long-term staph infections on their skin, though the germs do not always cause symptoms.

This study looked at two kinds of antibiotic proteins, called beta-defensins and cathelicidins. Both usually are found in large numbers in inflamed skin. Several years ago, large amounts also were found in the skin of people who have psoriasis, explaining why they get fewer skin infections than most people.

But when researchers looked at eight eczema patients' infected patches, they found none or nearly none of the chemicals.

"I think it is the beginning of a new type of thinking in medicine," said Dr. Enno Christianson, a scientist at the University of Kiel in Germany who discovered a number of human defensins.

Christianson said the study opens a new way to look at the body's defenses, since it does not involve the immune system but the epithelium, the body's surface tissue. Other defensins are created in mucous membranes and tissues lining the gut and the bronchial system.

Dr. Jon Hanifin of Oregon Health Sciences University, a member of the National Eczema Association's scientific advisory committee, said the researchers might have gone too far with their conclusions.

He said it is not at all clear whether the lack of the antibiotic proteins is a cause or effect: "It could be there's so much staph on the skin that it soaks up these defensins."

The study suggests that the body's allergic response suppresses production of these antibiotics. That means drugs already being tested against allergies and asthma might also help eczema sufferers get rid of skin infections, said the lead researcher, Dr. Donald Leung of the National Jewish Medical and Research Center in Denver.

Another researcher who worked on the study, Dr. Richard L. Gallo of the Veterans Affairs San Diego Healthcare System and the University of California at San Diego, said protein antibiotic creams now under development might also help.

Copyright 2002 Associated Press.

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ABBOTT LABS REPORTS PROGRESS FOR ARTHRITIS DRUG
By Ted Griffith, CBS.MarketWatch.com

CHICAGO -- Abbott Labs' new treatment for rheumatoid arthritis has shown considerable promise in combating the debilitating disease, according to data released by the company. In an announcement released late Friday, its experimental drug, called Humira, halted bone destruction and improved quality of life in late-stage testing on patients with rheumatoid arthritis.

Doctors are detailing the results at a meeting of the American College of Rheumatology. Humira is seen by analysts as Abbott's most promising experimental drug and it could become a serious competitive threat to rheumatoid arthritis treatments now marketed by Amgen and Johnson & Johnson. The Abbott drug is expected to win U.S. Food and Drug Administration clearance next year.

Humira, also called D2E7, works in a way that's similar to J&J's Remicade and Amgen's Enbrel. All three drugs are designed to quiet the body's inflammatory response by interfering with an enzyme known as TNF.

Rheumatoid arthritis is an inflammatory condition that occurs when the immune system goes haywire and starts attacking healthy tissue. The painful, swelling condition can leave sufferers unable to work and care for themselves.

Humira appears to have an advantage over rival therapies because of more convenient dosing. The drug is taken by injection twice a month, while Amgen's Enbrel must be injected twice a week. Remicade is given by intravenous infusion and therefore is generally administered in a doctor's office, hospital or clinic.

Abbott said one study of Humira found that 62 percent of patients who received the drug "experienced no new bone erosions." The company said another late-stage study found a "statistically significant" improvement in quality of life among patients who received the experimental therapy.

However, some patients withdrew from the Humira trials because of " adverse events," including infections, Abbott acknowledged. In one study, withdrawals due to adverse events were 10 percent among Humira-treated patients compared with 6.5 percent for those getting a placebo.

More than 5 million people worldwide suffer from rheumatoid arthritis, according to statistics cited by Abbott. But the condition is much less prevalent than osteoarthritis, which doesn't involve the immune systems and affects most people in some way as they age.

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INFECTIONS MORE COMMON WITH RHEUMATOID ARTHRITIS
NEW YORK (Reuters Health)

People with rheumatoid arthritis (RA) have a higher-than-average rate of a wide variety of infections, particularly those affecting the joints, bones and skin, according to new study findings.

Frequent infections associated with RA have been reported for years, with patients showing a particular vulnerability to lung infections and septic arthritis--joint inflammation caused by invading bacteria. But because these reports have been based on hospitalized patients, the overall infection risk among people with RA has been unclear, the study authors point out.

In their look at people with and without RA living in Rochester, Minnesota, the researchers found that those with the disease were 70% more likely to acquire any infection over the study period.

The most frequent infections were septic arthritis, a bone infection called osteomyelitis and infections of the skin and soft tissue, such as wound infections and shingles.

Dr. Sherine E. Gabriel and colleagues at the Mayo Clinic in Rochester reported the findings in a recent issue of the journal Arthritis & Rheumatism.

Rheumatoid arthritis occurs when the immune system, for unknown reasons, mistakenly attacks the joints, leading to inflammation, swelling and pain. Over time, this process erodes the bone and soft tissue within the joints. Because of the abnormal immune assault, drugs that suppress components of the immune system are central in RA treatment.

According to Gabriel's team, these drugs, the disease itself, or RA-related factors such as the need for joint surgery could be responsible for the heightened infection rate.

"These results," the study authors write, "underscore the need for additional research to discover the determinants of this increased infection risk in RA."

For the study, the researchers reviewed the medical records of 609 adults with RA diagnosed between 1955 and 1994, and compared each patient with an adult the same age and sex without RA. Participants, more than 73% of whom were women, were followed for 13 to 15 years, on average.

The researchers found that septic arthritis was 15 times more common among RA patients. Osteomyelitis was nearly 11 times more common, and skin and soft-tissue infections more than three times as common. Increased risks were also found for infections of the lungs and abdominal organs, among others.

SOURCE: Arthritis & Rheumatism 2002 Copyright © 2002 Reuters Limited.

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HUMANIZED OKT3 MONOCLONAL ANTIBODY MAY BE USEFUL FOR PSORIATIC ARTHRITIS By Megan Rauscher NEW YORK (Reuters Health)

Results of a phase I/II clinical trial indicate that treatment with a humanized derivative of OKT3, the anti-CD3 monoclonal antibody (Mab), is safe and may be efficacious in patients with psoriatic arthritis.

The non-Fc receptor (FcR)-binding derivative, designated huOKT3-gamma-1(ala-ala), "is a modification of Mab OKT3 with decreased immunogenicity and inability to bind FcR, resulting in less toxicity than conventional OKT3," Dr. Marcus R. Clark of the University of Chicago and colleagues explain in the Journal of Rheumatology for September.

In comments to Reuters Health, Dr. Clark said, "huOKT3gamma1(ala-ala) specifically targets immunological processes which may redirect the immune response away from autoimmunity and holds the promise of inducing drug-free remissions. In contrast, most therapies currently used to treat autoimmune diseases, such as psoriatic arthritis, are immunosuppressives. You take the drug away and the disease recurs."

Dr. Clark's team treated 7 patients with psoriatic arthritis with escalating doses of huOKT3 for 12 to 14 days. While initiating doses differed, all subjects received 8 to 10 days of treatment at the maximum dose of 4.0 mg/day.

Thirty days after treatment, 6 of the 7 patients had at least 75% improvement in the number of inflamed joints and an average 63% improvement on the patient pain scale. Despite this "remarkable initial clinical response," symptoms recurred in 4 of 6 responders by 90 days.

No patient developed severe symptoms associated with "cytokine release syndrome" as has been the case in studies of conventional OKT3 therapy.

These findings suggest that huOKT3-gamma-1(ala-ala) "may provide some lasting benefit to patients with psoriatic arthritis," Dr. Clark told Reuters Health. "This is to be tested in a multicenter phase II, placebo-controlled trial that should be starting early next year."

Dr. Clark said the current trial is "one of the first uses of non-FcR binding antibodies in the treatment of a chronic autoimmune disease. It also has been used to treat diabetes."

J Rheumatol 2002;29:1907-1913.

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Keep the faith. There are many dedicated individuals in the worlds' scientific, medical, and pharmaceutical communities, working every day to find answers to Psoriasis, Psoriatic Arthritis, and the countless other related diseases that affect our daily lives.

Good Health to All

Jack Nicholas
Newsletter Editor
Cornishpro@aol.com
Issue 2002 10/31/02-23