Physical Therapy As Effective As Arthroscopic Knee Surgery, New Research Finds

A new study questioning the usefulness of arthroscopic surgery for osteoarthritis of the knee should encourage patients to consider physical therapy as an effective non-surgical option, according to the American Physical Therapy Association (APTA). The study was published in the New England Journal of Medicine (NEJM).



The study found that physical therapy, combined with comprehensive medical management, is just as effective at relieving the pain and stiffness of moderate to severe osteoarthritis of the knee as surgery.



"This study offers hope and encouragement to persons with osteoarthritis who would like to avoid the pain and emotional toll of surgery," said APTA President R Scott Ward, PT, PhD. "Too often, the first line of defense is surgery when it need not always be. Physical therapy can be equally effective and should be considered by not only patients themselves, but also the primary care doctors and orthopedists who are treating them."



According to physical therapist Christopher M Powers, PhD, PT, director of the Biokinesiology program and co-director of the Musculoskeletal Biomechanics Research Lab at the University of Southern California Division of Biokinesiology & Physical Therapy, "Many times knee pain is associated with abnormal movement patterns that cause increased stress on the joint. Arthroscopic surgery does little to correct the dynamic factors that may be contributing to knee pain and pathology. These findings reinforce the need for a comprehensive treatment approach for such patients."



The NEJM study adds to a growing body of evidence supporting physical therapy for treatment of osteoarthritis of the knee, including:
A report published in the January 2008 issue of the journal Physical Therapy that reviewed research on osteoarthritis of the knee from 2000 to 2007 and found "high-quality evidence that exercise and weight reduction reduce pain and improve physical function."


A study published in the Feb 1, 2000 issue of the Annals of Internal Medicine that concluded "a combination of manual physical therapy and supervised exercise yields functional benefits for patients with osteoarthritis of the knee and may delay or prevent the need for surgical intervention."

A physical therapist will perform a thorough examination and design a plan of care that may include:
A series of exercises designed to help improve motion. Activities in this phase might include water walking, swimming, and flexibility exercises.


An exercise sequence to restore strength including a functional progression, that is, a gradual return to normal activities using exercises that simulate the knee stresses of your normal activities.

A knee's tolerance for stressful activities often decreases with age and loss of conditioning. As a result, stresses that would not have caused pain or injury to the knee last year could today. A decrease in levels of activity over a period of time may also contribute to the vulnerability of knees.
















But there are steps one can take to help prevent injury in order to continue enjoying sports and exercise. Pursuing an exercise program designed by a physical therapist can be one of the best protections from injury.



The first step in designing your exercise program is an evaluation by your physical therapist. He or she can identify your predisposing factors, those body traits that may make you more or less vulnerable to a knee injury. Based on this evaluation, your physical therapist can design a program that will help you gain your optimum levels of function, strength and conditioning.



Physical therapy plays a key role in treating and rehabilitating the knee, but the patient's attitude toward recovery plays a big factor in achieving a successful outcome. For more information on taking care of your knees and to find a physical therapist, visit apta/consumer/.







APTA (apta/) is a national organization representing physical therapists, physical therapist assistants, and students nationwide. Its goal is to foster advancements in physical therapist education, practice, and research. Consumers can visit findapt.us / to find a physical therapist in their area, as well as apta/consumer/ for physical therapy news and information.



Source: Stephanie Block


American Physical Therapy Association

Joint Inflammation And Heart Disease Linked

People coping with rheumatoid arthritis or lupus already have a lot to deal with. Even so, paying attention to heart health may be especially important for this group. The August 2008 issue of the Harvard Heart Letter reports that rheumatoid arthritis doubles a person's risk of heart attack or cardiac arrest. Heart disease risk is even higher with lupus, and a new study suggests that gout, another common kind of arthritis, is also linked to cardiovascular disease.


Rheumatoid arthritis, lupus, and related autoimmune disorders are caused by a misguided immune system. Certain white blood cells, which ordinarily protect the body from infection, attack its tissues instead. Although no one knows exactly how these conditions are connected to cardiovascular disease, it is possible they all spring from the same source inflammation.


Inflammation is an essential part of the body's defenses. In people with rheumatoid arthritis and lupus, though, inflammation turns against the body and damages joints and other tissues. In heart disease, inflammation kicks off artery-clogging atherosclerosis, keeps it smoldering, and influences the formation of clots, the ultimate cause of heart attacks and many strokes.


Controlling rheumatoid arthritis or lupus with medications that calm inflammation may be a good start toward reducing the excess risk of heart disease. Some studies show that using medications like Remicade and Humira reduces the likelihood of having heart attacks. Statins and baby aspirin may also help.


For now, the Harvard Heart Letter suggests that the best way to control heart risk is by paying attention to diet, weight, exercise, blood pressure, and cholesterol.


Harvard Health Publications

Harvard Medical School 10 Shattuck St., Ste. 612

Cambridge, MA 02115

United States

health.harvard



View drug information on Humira; Remicade.

Know The Facts Before Hip Replacement

On the golf course, in the garden, or at the shopping mall, most people want to stay active, regardless of age. As the number of Americans reaching their 60s grows daily, the demand for mobility-restoring procedures, such as hip replacement, is steadily increasing.


Total joint replacement is thought to be among the most valued developments in the history of orthopedics. It has evolved into a reliable and effective way to relieve pain and restore function to joints that have been damaged or destroyed by arthritis or injury. Joint replacement makes it possible for patients to resume their active lives, say the Adult Reconstruction and Joint Replacement experts at Hospital for Special Surgery in New York, a world leader in orthopedics and rheumatology.


Although the best weight-bearing surface is human cartilage, when the damage is too great, manmade materials, in the form of an artificial joint, become an option. Before undergoing a joint replacement procedure, it's important for people to learn from their doctor, what is involved in the surgery and to have realistic expectations.


The team at Hospital for Special Surgery, whose surgeons have performed more hip replacements and knee surgeries than any other institution in the world, emphasize that it is a major operation. Hip replacement also can be life-changing for someone who is debilitated by severe joint damage.


One of the important developments in hip replacement is the number of options available for artificial joints. Patients considering hip replacement surgery should count on their surgeon to work with them in selecting the right type of implant design and material. When planning for surgery, the doctor and patient should consider a range of factors, such as the patient's age, weight, bone strength, the shape of the person's bones, as well as a patient's lifestyle and activity level.


Type of Implants


Today, a new joint can be made out of polished metal or ceramic, with some featuring a combination of plastic liner and cobalt-chrome or titanium backing.


Metal and Plastic


Metal and plastic implants are the most commonly used hip replacements. One of the most often used bearing surface combinations is metal on polyethylene, a form of plastic that provides marked durability.


Ceramic


Ceramics are used in total joint replacements, specifically to provide more wear-resistant bearing surfaces. Because of their hardness, ceramics can be polished to a very smooth finish and remain relatively scratch resistant while in use. Ceramic bearings are more subject to fracture than other materials. Most patients whose active lifestyles subject them to repetitive impact are not good candidates for ceramic bearings, nor are patients with high body weight.


Metal-on-Metal


Metal-on-metal implants have been developed to function without a plastic piece inserted between them. These implants do not wear out as quickly as the plastic/metal versions and work well with young, active patients. There is concern that normal use may result in the release of microscopic metal particles that can lead to inflammation and loosening. Tests have also found elevated levels of metal ions in the blood but so far it hasn't been shown that these levels result in harm.


Although researchers are constantly seeking ways to improve implant design and durability, today there is no clear-cut kind of implant that is viewed as superior. Most surgeons will agree that the decision about joint implant materials is individual and should be decided by the patient and doctor together.


Says Dr. Mark P. Figgie, chief of the Surgical Arthritis Service at Hospital for Special Surgery, "I always spend a lot of time with my patients going over all the options and listening to them to learn what their needs and expectations are. The patients find the time we spend together talking about their needs and expectations invaluable. Once this process is completed and I feel that they are sufficiently informed, it is always up to the patient to decide."


For more information about joint replacement. visit: hss/ARJR


Source

Hospital for Special Surgery

Many Rheumatology Patients Have Low Health Literacy

Many patients seen at a rheumatology clinic-including some with a long history of rheumatoid arthritis (RA)-don't recognize important terms related to their health and medical treatment, reports a study in the December issue of JCR: Journal of Clinical Rheumatology. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health, a leading provider of information and business intelligence for students, professionals, and institutions in medicine, nursing, allied health, and pharmacy.


"More than 10 percent of patients who had been living with RA for an average of 11 years could not read the words osteoporosis, inflammatory, rheumatologist, cartilage, and symptom correctly," according to the new research, led by Christopher J. Swearingen, Ph.D., of University of Arkansas for Medical Sciences, Little Rock. The results add to recent evidence identifying low health literacy as a common problem that may contribute to poor health outcomes.


Low Health Literacy Is Frequent, Linked to Worse Outcomes


The study included 194 patients seen at a university Rheumatology clinic. Health literacy was assessed using two word lists: one listing terms related to general health and medicine and the other including words specifically related to rheumatology and arthritis. Health literacy scores were compared with the patients' health and other characteristics.


Many patients had low health literacy, with scores indicating an eighth-grade reading level or less. This included 18 percent of patients on the general health literacy test and 24 percent on the rheumatology-specific word list. None of the patients had severely low literacy, defined as a third-grade reading level or less.


More than ten percent of patients didn't recognize common health terms like diagnose and symptom. Even though most of the patients had been seeing a rheumatologist for some time, 13 percent did not recognize common words related to rheumatology and arthritis, such as cartilage and anti-inflammatory.


Eleven percent of patients didn't recognize the word rheumatologist. Even higher percentages didn't recognize the names of common arthritis drugs, such as methotrexate or Naprosyn.


Patients with lower health literacy scores tended to have lower education and to be in worse health. Scores on the two word lists were closely related to each other, suggesting that general health literacy was a good indicator of rheumatology-specific health literacy.


The results are consistent with previous studies reporting that 14 percent of U.S. adults have "below basic literacy skills." Low literacy is strongly related to low education-which in turn is associated with increased rates of RA and other rheumatic diseases.


"Low literacy may be a mutable risk factor for poor health and outcomes in rheumatic and other chronic diseases," the researchers write. They think it's likely their study underestimates the true extent of the relationship between low literacy and poor health.


What can doctors' offices do to help address the problem of low health literacy? Following the U.S. Department of Health and Human Services' National Action Plan to Improve Health Literacy may help patients to develop self-management skills and enhance their ability to access and use health information, Dr. Swearingen and co-authors believe. They conclude, "Reduction of literacy-related barriers may help to narrow widening disparities in health according to socioeconomic status."


Source:

Wolters Kluwer Health: Lippincott Williams & Wilkins

FDA Should Have Announced Conflicts Among COX-2 Inhibitor Committee Members, Editorial States

Although "there was nothing illegal" about the appointment of scientists with past financial ties to... Pfizer, Merck and Novartis to a joint FDA advisory committee on the safety of COX-2 inhibitors, the agency "can be faulted for its failure to announce the conflicts at the time of the meeting," a New York Times editorial states (New York Times, 3/4). According to a recent review conducted by the Center for Science in the Public Interest, 10 members of the committee had past financial ties to pharmaceutical companies that market COX-2 inhibitors. The committee voted to recommend that FDA allow the COX-2 inhibitors Celebrex and Bextra, both manufactured by Pfizer, to remain on the market and that the agency allow the COX-2 inhibitor Vioxx, manufactured by Merck, to return to the market (Kaiser Daily Health Policy Report, 2/28). According to the editorial, without the votes of those 10 scientists, the committee "would have favored withdrawing Bextra from the market and blocking the return of Vioxx" and would have recommended that FDA allow only Celebrex to remain on the market, the review found. However, the "deeper problem is that links between drug companies and medical researchers are pervasive," the editorial states. The editorial concludes, "Unless the FDA makes a more aggressive effort to find unbiased experts or medical researchers start severing ties with industry, a whiff of bias may taint the verdicts of many advisory panels" (New York Times, 3/4).


"Reprinted with permission from kaisernetwork kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.


View drug information on Bextra; Vioxx.

Physician-Scientist Urges Improved Drug Regulation To Ensure Heart Safety Of Non-Heart Drugs

Current regulatory policies should be strengthened to ensure acceptable cardiovascular safety of drugs developed primarily for non-cardiovascular medical problems, according to a recent presentation made by Dr. Jeffrey Borer, an authority in cardiovascular medicine and surgery at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City.


His recommendations include earlier testing of all drugs' cardiovascular effects and giving regulatory bodies the authority to mandate continuing evaluation of drug effects, even after approval for marketing.


"The importance of evaluating the cardiovascular safety of new drugs has been highlighted by recent examples of drugs - anti-arthritis drugs and others - that were withdrawn from the market when unacceptable cardiovascular risks were discovered after regulatory approval," says Dr. Borer. "It is clear that drugs intended for non-cardiovascular problems must be more fully scrutinized than in the past in order to allow doctors and patients to be assured that risks are well defined and that they do not outweigh the benefits provided by the drugs for the individual patient. The primary strategy to achieve this goal is increasing formal observations in both pre- and post-approval studies."


Specific recommendations include:


-- Cardiovascular safety assessment should be incorporated in drug development beginning with animal studies of drug effects on cardiac physiology/pharmacology, even if the drug is not intended for cardiovascular problems. Similarly, evaluation of cardiovascular effects should begin in the earliest phases of drug testing in patients. The definitions of adverse cardiovascular events like heart attacks and strokes should be standardized for all observers before the drug is administered to any patient. (Currently, for drugs not intended for heart problems, cardiovascular effects often are assessed only minimally, generally in later phases of drug development. And, the definition of adverse events is left up to each observer individually, limiting the strength of conclusions about cardiovascular safety.)


-- Regulatory bodies should be given the authority to mandate continuing evaluation of drug effects, even after approval for marketing. This will allow updates in drug labeling to increase the precision with which doctors and patients can know the relation of benefit and risk, enabling the best decisions about selection of treatment strategies.


-- Regulatory bodies should be empowered to withdraw approval if mandated post-marketing studies are not performed. Currently, the FDA, for example, does not have such authority.


-- If the drug is likely to be used by people who have relatively high cardiovascular risk (as, for example, might be the case with a drug for arthritis), at least one study of the drug's beneficial effects should be carried out among such patients, not only in low risk people as is now commonly the case.















-- Analysis plans should be designed to incorporate all data collected during development, including results of so-called observational studies (which do not employ randomization to eliminate study bias, and which do not employ "control" groups for comparison) in order to increase statistical power to find problems if they exist. Currently, this kind of analysis plan is not usually employed.


Dr. Borer's presentation was made at the recent annual meeting of the European Society of Cardiology in Vienna, and was drawn in part from his article in the Aug. 2007 issue of the European Heart Journal. This paper summarizes the conclusions of a group of co-authors - including cardiologists, biostatisticians, FDA and EMEA (European Medicines Agency Home) regulators and representatives from the NIH and the pharmaceutical industry - who had met previously at a Cardiovascular Clinical Trialists roundtable in Paris to consider these issues.


Jeffrey S. Borer has been an FDA advisor since 1977 and served three terms as Chair of the FDA's Cardio-Renal Drugs Advisory Committee between 1982 and 2004. He is director of the Howard Gilman Institute for Valvular Heart Diseases at NewYork-Presbyterian/Weill Cornell and the Gladys and Roland Harriman Professor of Cardiovascular Medicine and professor of cardiovascular medicine in cardiothoracic surgery at Weill Cornell Medical College.


The Howard Gilman Institute for Valvular Heart Diseases at NewYork-Presbyterian/Weill Cornell helps cardiologists, cardiothoracic surgeons and other physicians take advantage of the most current concepts in the evaluation and treatment of heart valve diseases and provides state-of-the-art patient care. The Institute's co-directors, Dr. Jeffrey S. Borer and Dr. O. Wayne Isom, are leaders in their fields and direct a team of clinical cardiologists, surgeons and research scientists who are at the cutting-edge of this emerging public health concern. For more information, visit gilmanheartvalve.


NewYork-Presbyterian Hospital/Weill Cornell Medical Center


NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances - from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial for gene therapy for Parkinson's disease, the first indication of bone marrow's critical role in tumor growth, and, most recently, the world's first successful use of deep brain stimulation to treat a minimally-conscious brain-injured patient. NewYork-Presbyterian, which is ranked sixth on the U.S.News & World Report list of top hospitals, also comprises NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children's Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Westchester Division and NewYork-Presbyterian Hospital/The Allen Pavilion. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree overseas and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar. For more information, visit nyp and med.cornell.

In Arthritis Patients Taking NSAIDs, NT-ProBNP Is A Predictor Of CV Risk

The role of N-terminal pro-B-type natriuretic peptide (NT-proBNP, a protein thought to be a regulator of cardiovascular function) as a robust, non-invasive predictor of cardiovascular (CV) risk in patients with arthritis taking cyclooxygenase inhibitors has been reinforced by the results of a multinational study presented at EULAR 2010, the Annual Congress of the European League Against Rheumatism in Rome, Italy.



The presence of NT-proBNP was associated with a range of CV outcomes, including CV death (p= < 0.0001), myocardial infarction (MI) (p=0.02), heart failure (HF) (p=0.004) and a composite of thrombotic events (CV death, MI, or stroke) (p= < 0.0001). This marker for CV risk remained strongly predictive of CV events after adjustment for age, sex, diabetes, hypertension, type of arthritis, body mass index (BMI), renal function and history of prior CV disease. The results of this multinational trial, which involved The Thrombolysis in Myocardial Infarction (TIMI) Study Group, evaluated 2-year CV outcomes in 6,273 patients with rheumatoid arthritis (RA) and osteoarthritis treated with the non-steroidal anti-inflammatory treatments etoricoxib or diclofenac.



"This study has validated previous research showing that NT-proBNP is a strong indicator for cardiovascular risk in arthritis patients," said Professor Kay Brune, lead author, Department of Pharmacology, University of Erlangen, Erlangen, Germany. "This means that clinically, the presence of NT-proBNP can be used to accurately assess a patients' CV risk, meaning that appropriate treatment options can be identified early on."



Furthermore, the assessment of CV disease risk in patients with Rheumatoid Arthritis (RA) was studied in a separate 15-year follow-up study of Norwegian patients. The study aimed to determine whether early markers of RA inflammatory disease activity could predict arterial stiffness, a surrogate marker of CV disease. Arterial stiffness was measured as Pulse Wave Velocity (PWV) and Augmentation Index (AIx).



"From this research, we can now say that certain inflammatory markers seem to be independent, longitudinal predictors of CV risk in RA patients. Treatment options that help manage early inflammation in patients with RA may ensure that the long-term CV risk associated with RA is managed appropriately," said Dr. Sella Provan, Diakonhjemmet Hospital, Oslo, Norway, and lead author of the study.



In the Norwegian study, patients with elevated baseline C-reactive protein (CRP, a blood protein, levels of which may rise in response to certain types of inflammation) had a significantly higher AIx Beta co-efficient Confidence Interval (??(CI) 2.67 (0.06-5.31) p=0.045) and PWV after 15 years (??(CI) 0.08 (0.01-0.14) p=0.02) after adjustments for age, sex and mean arterial pressure (MAP). Baseline elevated CRP remained a significant predictor of increased AIx after adjustment for possible current confounders.



Abstract Numbers: OP0010 & SAT0039



Source:

Rory Berrie


European League Against Rheumatism

Three Studies Suggest Abbott's HUMIRA (adalimumab) May Improve Work Productivity In Patients With Rheumatoid Arthritis

Rheumatoid arthritis (RA) is one of the most common causes of disability in the Western world. New data released today show that rheumatoid arthritis (RA) patients treated with Abbott's HUMIRA(TM) (adalimumab) stayed working longer, had fewer absences and reported greater improvements in work performance.


Results from three studies were presented today at the European League Against Rheumatism (EULAR) annual congress in Barcelona. One groundbreaking study, PRevention Of Work Disability (PROWD), investigated the effect that HUMIRA therapy can have on the length of time RA patients remain at work. This was the first prospective, placebo-controlled, anti-tumor necrosis factor (TNF) study that investigated this effect. PROWD showed that significantly more patients taking methotrexate (MTX) alone reported job loss or imminent job loss after 56 weeks compared with those treated with a combination of HUMIRA and MTX.


A second study of patient-reported measures in paid workers and homemakers with early RA suggested that treatment with HUMIRA and MTX significantly improved their ability to perform their responsibilities at two years. A third study showed that RA patients treated with HUMIRA worked significantly longer compared with patients taking disease-modifying anti-rheumatic drugs (DMARDs).


"The data show that treatment with HUMIRA may allow patients to be more productive both at home and in the workplace," said Paul Emery, M.D., professor of rheumatology, Leeds University, UK.


Five million people worldwide - mostly between the ages of 25 and 55 - are currently living with RA, which most often affects the hands, feet and wrists. Typically, joint damage can occur within two years of the onset of the disease. RA can interfere with a person's ability to work due to joint pain, fatigue and joint tenderness and damage. Several studies have shown that patients with RA have limited employment possibilities and reduced productivity at work.


Study Highlights:


-- PROWD is a multi-center, randomized, 56-week controlled trial that examined the effect of HUMIRA plus MTX versus placebo plus MTX on job loss due to all causes and imminent job loss in 148 early RA patients. Although the changes in job loss related to all causes - not specific to disability alone - did not reach significance between weeks 16 and 56, results showed that significantly more patients on MTX alone reported job loss compared to patients taking HUMIRA plus MTX during the entire period of 56 weeks (40 percent vs. 19 percent). The investigators concluded that HUMIRA plus MTX reduced RA-related job loss and reduced work time lost in patients with early RA more than MTX alone.
















-- DE032 is an economic companion study to PREMIER, a two-year, double-blind controlled study that compared the effectiveness of HUMIRA, MTX and the combination of the two drugs in treating early RA. The DE032 study compared HUMIRA plus MTX (n=219) to MTX alone (n=214) on patient-reported measures of work performance in both paid workers and homemakers. Results showed that after two years, paid workers and homemakers taking MTX alone missed significantly more workdays than patients taking HUMIRA plus MTX
(26 vs. 15 and 14 vs. 7, respectively). In addition, patients on HUMIRA plus MTX were 21 percent more likely to gain or retain employment compared to patients on MTX alone at the end of two years.



-- DE033, an open label DMARD registry controlled study, examined the
long-term impact on employment tenure and likelihood of stopping work over
24 months for RA patients on HUMIRA versus those on a DMARD. Multivariate regression analyses controlled for the baseline characteristic differences between the two populations while comparing the outcomes. Over the two-year period, patients working at the time of study enrollment in the HUMIRA group worked more than seven months longer and were 36 percent less likely to stop working than the patients in the DMARD registry.


"Rheumatoid arthritis can have a profound impact on the lives of patients. Within three years of diagnosis some people who develop the condition have to give up
full-time employment," said Rebecca Hoffman, M.D., divisional vice president, Immunology Development, Abbott. "The results of the studies suggest the benefit of HUMIRA combined with MTX extends beyond the clinical scope."


HUMIRA is approved to treat adult patients with moderately to severely active rheumatoid arthritis. More than 190,000 patients worldwide are currently being treated with HUMIRA.



About Rheumatoid Arthritis


Unlike osteoarthritis, the most common form of arthritis, RA is an autoimmune disease where joints are inflamed, which may lead to damage of the joints' interior and the surrounding bone. The joints most commonly affected during the beginning of the disease are the smaller joints of the fingers, feet and wrists. The elbows, knees, ankles and hips can be affected, but less often. Although there is no cure for RA, people continue to seek treatments that not only alleviate the pain and inflammation but also slow disease progression, thereby inhibiting the joint damage that can hinder patients from performing daily activities.


More information on RA and current treatment options can be found at RA.


Important Safety Information About HUMIRA


Globally, prescribing information varies; refer to the individual country product label for complete information. For U.S. safety information, visit HUMIRA.


Serious infections, sepsis, rare cases of tuberculosis (TB), and opportunistic infections, including fatalities, have been reported with the use of TNF antagonists, including HUMIRA. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy that, in addition to their RA could predispose them to infections. Patients must be monitored closely for infections, including tuberculosis, before, during and after treatment with HUMIRA. Treatment should not be initiated in patients with active infections until infections are controlled. HUMIRA should not be used by patients with active TB or other severe infections such as sepsis and opportunistic infections. Patients who develop new infections while using HUMIRA should be monitored closely. HUMIRA should be discontinued if a patient develops a new serious infection until infections are controlled. Physicians should exercise caution when considering use of HUMIRA in patients with a history of recurring infection or with underlying conditions that may predispose patients to infections.


TNF-blocking agents have been associated with reactivation of hepatitis B (HBV) in patients who are chronic carriers of the virus. Some cases have been fatal. Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating HUMIRA.


The combination of HUMIRA and anakinra is not recommended.


TNF antagonists, including HUMIRA, have been associated in rare cases with demyelinating disease and serious allergic reactions. Rare reports of pancytopenia including aplastic anemia have been reported with TNF-blocking agents. Adverse events of the haematologic system, including medically significant cytopenia have been infrequently reported with HUMIRA.


More cases of malignancies including lymphoma have been observed among patients receiving a TNF antagonist compared with control patients in clinical trials. The size of the control group and limited duration of the controlled portions of studies precludes the ability to draw firm conclusions. Furthermore, there is an increased background lymphoma risk in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, which complicates the risk estimation. During the long-term open-label trials with HUMIRA, the overall rate of malignancies was similar to what would be expected for an age, gender and race matched general population. With the current knowledge, a possible risk for the development of lymphomas or other malignancies in patients treated with a TNF antagonist cannot be excluded.


In clinical studies with another TNF antagonist, a higher rate of serious congestive heart failure (CHF) related adverse events including worsening CHF and new onset CHF have been reported. Cases of worsening CHF have also been reported in patients receiving HUMIRA. Physicians should exercise caution when using HUMIRA in patients who have heart failure and monitor them carefully. HUMIRA should not be used in patients with moderate or severe heart failure.


The most frequently reported adverse event (>1/10 patients) at least possibly causally related to HUMIRA is injection site reaction (including pain, swelling, redness or pruritus). Other common adverse events (reported by >1/100 patients) at least possibly causally related to HUMIRA include lower respiratory infections (including pneumonia, bronchitis), viral infections (including influenza, herpes infections), candidiasis, bacterial infection (including urinary tract infections), upper respiratory infection, lymphopenia, dizziness (including vertigo), headache, neurologic sensation disorders (including paraesthesias), infection, irritation or inflammation of the eye, cough, nasopharyngeal pain, diarrhea, abdominal pain, stomatitis and mouth ulceration, nausea, hepatic enzymes increased, rash, dermatitis and eczema, pruritus, hair loss, musculoskeletal pain, pyrexia, fatigue (including asthenia and malaise).


About HUMIRA


HUMIRA is the only fully human monoclonal antibody approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS, an arthritis of the spine) and Crohn's disease in the U.S. and Europe. HUMIRA resembles antibodies normally found in the body. It works by blocking tumor necrosis factor alpha (TNF-?±), a protein that when produced in excess, plays a central role in the inflammatory responses of immune-mediated diseases. To date, HUMIRA has been approved in 67 countries with more than 190,000 people worldwide currently treated with HUMIRA. Clinical trials are currently under way evaluating the potential of HUMIRA in other immune-mediated diseases.


In Europe, HUMIRA, in combination with methotrexate (MTX), is indicated for the treatment of moderate to severe, active RA in adult patients when the response to disease-modifying anti-rheumatic drugs (DMARDs) including MTX has been inadequate, and for the treatment of severe, active and progressive RA in adults not previously treated with MTX. HUMIRA can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. HUMIRA has been shown to reduce the rate of progression of joint damage as measured by x-ray and to improve physical function, when given in combination with MTX. Additionally, HUMIRA is indicated for the treatment of active and progressive PsA in adults when the response to previous DMARD-therapy has been inadequate and for the treatment of severe, active AS in adults who have had an inadequate response to conventional therapy.


About Abbott


Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs 65,000 people and markets its products in more than 130 countries.


Abbott's news releases and other information are available on the company's Web site at abbott


View drug information on Humira.

Significant Improvement In Asthma And Osteoarthritis After Bariatric Surgery - Most No Longer Require Steroids Within 18 Months

Most patients with asthma and osteoarthritis were able to stop taking steroids within 18 months of bariatric surgery, according to a new study presented here at the 25th Annual Meeting of the American Society for Metabolic & Bariatric Surgery (ASMBS).



Researchers from The Western Pennsylvania Hospital, a teaching hospital of Temple University School of Medicine in Pittsburgh, studied 49 morbidly obese patients who were taking steroids and other immunosuppressive medications to treat chronic inflammatory diseases including asthma and osteoarthritis, and autoimmune diseases such as rheumatoid arthritis and myasthenia gravis. These patients, with an average body mass index (BMI) of 47, had bariatric surgery sometime between 1999and 2008.



Eighteen months after bariatric surgery more than half of the patients had so much improvement in their inflammatory or autoimmune disease, they were able to stop taking or significantly reduce the use of oral steroids or immunosuppressive medications, powerful treatments that manage disease but also produce numerous adverse effects, particularly after prolonged use. Patients had an average excess weight loss of 65.2 percent and other obesity-related diseases including type 2 diabetes and obstructive sleep apnea were resolved or improved in more than 80 percent of patients. There were 8 early complications and no deaths.


"Patients with compromised immune systems or taking steroids for chronic inflammatory diseases may have been excluded from bariatric surgery because they are at higher risk for complications related to their disease or immunosuppressant medications," said Daniel J. Gagn?©, MD, the study's lead author and Director of Bariatric Surgery and Laparoscopic and Minimally Invasive Surgery at The Western Pennsylvania Hospital. "However, this study shows not only can these patients safely have bariatric surgery, but they can achieve significant improvements or elimination of many diseases."



Study Results - Highlights



All nine patients with asthma or chronic obstructive pulmonary disease (COPD) were able to discontinue use of oral steroids after surgery. Seven more were able to discontinue use of inhaled steroids, one had reduced frequency and one was unchanged after 18 months. Five patients with osteoarthritis were able to discontinue use of oral steroids and one was able to decrease dosage and two of the four patients with rheumatoid arthritis were able to stop taking oral steroids and two others required lower doses of other medications. Of the six patients with psoriasis, two were able to discontinue the use of topical steroid cream and one discontinued the use of cyclosporine. Two others decreased dosages of other psoriasis medications and one remained unchanged.The four patients with Myasthenia Gravis had improvement in their condition after bariatric surgery and were able to decrease the frequency of treatment or immunosuppressant dosage. Researchers found that not all patients with immunosuppressive diseases saw changes. The patients with Lupus or Multiple Sclerosis had no change in their immunosuppressive diseases or medications. Resolution or improvement of other obesity-related diseases was consistent with previous studies. Type 2 diabetes was improved or resolved in 95 percent of patients; high blood pressure in 80 percent; obstructive sleep apnea in 96 percent; and GERD in 85 percent.
















Dr. Gagn?© says immunocompromised patients can present special challenges and surgeons must carefully evaluate individual patient risk factors, disease severity, and type of medication before surgery.


In 2007, the ASMBS reported that an estimated 205,000 people in the U.S. had bariatric surgery. According to guidelines issued by the National Institutes of Health (NIH), bariatric surgery is indicated for people with a body mass index (BMI) of 35 or more with an obesity-related condition or a BMI of 40 or more. People who are morbidly obese are generally 100 or more pounds overweight.



The most common methods of bariatric surgery are laparoscopic gastric bypass and laparoscopic adjustable gastric banding (LAGB). In gastric bypass, the stomach is reduced from the size of a football to the size of a golf ball and food is made to bypass part of the small intestine. In LAGB, a silicone band is wrapped around the upper part of the stomach to restrict the amount of food the stomach can hold. The amount of restriction is adjusted by adding or removing saline from the band.



Two landmark studies, published in the New England Journal of Medicine in August 2007, showed patients with morbid obesity who had bariatric surgery lost significant weight and are significantly less likely to die from heart disease, diabetes and cancer seven to 10 years following the procedure than those who did not have surgery. [1], [2]



A 2004 study in the Journal of the American Medical Association showed that bariatric surgery resolved or improved type 2 diabetes in 86 percent of patients and resolved sleep apnea in more than 85 percent of patients [3].



The Agency for Healthcare Research and Quality (AHRQ) recently reported that bariatric surgery is safer than ever. The risk of death from bariatric surgery has declined from 0.89 percent in 1998, to 0.19 percent in 2004. [4]



About 64 million or 32 percent of adults in the U.S. are considered obese, which is associated with many other diseases and conditions including type 2 diabetes, heart disease, sleep apnea, hypertension, asthma, cancer, joint problems and infertility. The direct and indirect costs to the healthcare system associated with obesity are about $117 billion annually.



The ASMBS is the largest organization for bariatric surgeons in the world. It is a non-profit organization that works to advance the art and science of bariatric surgery and is committed to educating medical professionals and the lay public about bariatric surgery as an option for the treatment of morbid obesity, as well as the associated risks and benefits. It encourages its members to investigate and discover new advances in bariatric surgery, while maintaining a steady exchange of experiences and ideas that may lead to improved surgical outcomes for morbidly obese patients. For more information on the ASMBS, visit asmbs.

References

1. Sj?¶str?¶m L, Narbro K, Sj?¶str?¶m CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007; 357:741-52.


2. Adams TD, Gress RE, Smith SC, et al. Long-term mortality after gastric bypass surgery. N Engl J Med 2007:357:753-61.


3. Buchwald Henry, et al. Bariatric Surgery: A Systematic Review and Meta-Analysis. JAMA. 2004; 292: 1724-1737.


4. Zhao, Y. (Social and Scientific Systems, Inc.), and Encinosa, W. (AHRQ). Bariatric Surgery Utilization and Outcomes in 1998 and 2004. Statistical Brief #23. January 2007. Agency for Healthcare and Research Quality, Rockville, Md.hcup-us.ahrq/reports/statbriefs.sb23.pdf.

American Society for Metabolic & Bariatric Surgery

Endo Licenses U.S. Rights For Voltaren(R) Gel -- The First FDA-Approved Topical Treatment For Relief Of Osteoarthritis Pain

Endo Pharmaceuticals Inc., a wholly owned subsidiary of Endo Pharmaceuticals Holdings Inc. (NASDAQ: ENDP) and a market leader in pain management, announced that it has entered into a licensing agreement with Novartis to obtain the exclusive U.S. marketing rights for the prescription medicine Voltaren® Gel (diclofenac sodium topical gel) 1%.


Voltaren Gel received regulatory approval in October 2007 from the U.S. Food and Drug Administration, becoming the first topical prescription treatment for use in treating pain associated with osteoarthritis and the first new product approved in the U.S. for osteoarthritis since 2001. Voltaren Gel has been granted marketing exclusivity in the U.S. as a prescription medicine until at least October 2010.


Voltaren Gel, which is a nonsteroidal anti-inflammatory (NSAID) medication, is indicated for use in treating pain associated with osteoarthritis in joints amenable to topical treatment, such as the knees and those of the hands. Osteoarthritis is a chronic, painful condition characterized by the breakdown of cartilage in the joint, often leading to working limitations and reduced overall health.


Clinical trials have demonstrated Voltaren Gel to be highly effective in treating osteoarthritis pain in the hands and knees, which are the body's most commonly affected joints. Voltaren Gel delivers effective pain relief with a favorable safety profile as its systemic absorption is on average 6% of the systemic exposure from a comparable dose of an oral form of diclofenac sodium.


"Voltaren Gel is an ideal strategic and commercial fit for Endo. It is an approved product that we plan to launch in the U.S. as soon as possible," said Nancy J. Wysenski, Chief Operating Officer of Endo Pharmaceuticals. "We believe it will further enhance our leadership position in pain management by extending our reach into the mild-to-moderate segment of the osteoarthritis pain market while adding growth and diversification to our revenue base. In addition, Voltaren Gel will allow us to leverage our established expertise in marketing topical pain therapies. As a result, we expect market availability and momentum behind Voltaren Gel to build rapidly and provide broader access to patients in the U.S. suffering from pain associated with osteoarthritis."


Voltaren Gel will compete in the emerging topical NSAID market, which is expected to grow given the aging U.S. population. Of the estimated 84 million NSAID and Cox-II prescriptions written annually in the U.S., about 40% are osteoarthritis-related. The dollar value of this market is approximately $3.3 billion, with roughly half of the value coming from NSAIDs and the remainder from Cox-IIs. Endo estimates U.S. peak annual sales for Voltaren Gel in treating osteoarthritis pain in the range of $250-300 million.


Endo expects to commercialize Voltaren® Gel without delay, initially using one of its two specialty sales forces, consisting of 160 representatives, prior to executing a full physician launch in late May with an additional 275 contract sales representatives targeting primary care physicians who prescribe NSAIDs and Cox-IIs.















Under the terms of the five-year agreement with Novartis, Endo will make an upfront cash payment of $85 million. Novartis is also eligible to receive a one-time milestone payment of $25 million if annual sales exceed $300 million. Novartis will receive royalties on the net sales of Voltaren Gel in the U.S. and will supply this product to Endo.


As a result of today's announcement, Endo is revising its guidance for 2008. Net sales are now projected to be between $1.245 billion and $1.280 billion, up from the previous projections of $1.225 billion to $1.250 billion. Adjusted diluted earnings per share (excluding estimated milestone payments to partners and the expensing of stock-based compensation charges) for 2008 are now expected to be between $2.03 and $2.07, down from the prior adjusted diluted EPS guidance of $2.18 to $2.22. The change in EPS guidance reflects the impact of the additional field force, expected launch costs and amortization of the upfront payment associated with Voltaren Gel. Expectations are that Voltaren Gel will begin to be accretive to earnings in 2009, according to Charles A. Rowland, Jr., Chief Financial Officer.


The efficacy and safety of Voltaren Gel were studied in more than 900 patients with knee or hand osteoarthritis. The U.S. approval was based on several studies, including the results of two randomized, double-blind, placebo-controlled efficacy studies and a 12-month safety study. Voltaren Gel was shown to significantly reduce pain in hand and knee osteoarthritis, with pain relief sustained through the end of treatment. After six weeks of treatment in an efficacy study of patients with osteoarthritis of the hand, results showed that pain levels were reduced by nearly half (46%). In a 12-week study in patients with osteoarthritis of the knee, Voltaren Gel demonstrated a 51% reduction in pain.


Approximately 21 million people in the U.S. have osteoarthritis, [1] and the aging population in the U.S. means 72 million more may be at risk for developing the condition by 2030. [2]


About Osteoarthritis


Osteoarthritis is a chronic condition characterized by the breakdown of cartilage in the joint. Cartilage cushions the ends of the bones in joints -- such as knees, hands, elbows, wrists, ankles and feet -- which allows for easy movement. When cartilage erodes, bones can rub together, resulting in pain and loss of free movement in the joint. [3] The most common symptoms include pain, joint soreness, stiffness and deterioration of overall coordination, posture and walking.


Osteoarthritis is the leading cause of disability in the U.S., and the overall patient population for osteoarthritis and chronic joint pain is comparable in size to that of hypertension. Arthritis and related conditions, such as osteoarthritis, cost the U.S. economy nearly $128 billion per year in medical care and indirect expenses, including lost wages and production. [4] Despite the high prevalence of osteoarthritis, there is no cure for this disease, which tends to progressively reduce mobility and the overall health state in the affected patients.


About Voltaren® Gel


Voltaren Gel provides 1% diclofenac sodium in a topical gel formulation. It is a non-steroidal anti-inflammatory (NSAID) medication indicated for the pain of osteoarthritis in joints amenable to topical treatment, such as the knees and those of the hands. Voltaren Gel delivers highly effective pain relief with a favorable safety profile. The amount of diclofenac sodium that is systemically absorbed from Voltaren Gel is on average 6% of the systemic exposure from a comparable dose of an oral form of diclofenac sodium.


Important Safety Information


The most common adverse reactions reported in Voltaren® Gel clinical trials were application site reactions in 7% of treated patients. With all NSAIDs there may be an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. The use of Voltaren Gel is contraindicated in patients with a known hypersensitivity to diclofenac. Voltaren Gel should not be administered to patients who have experienced asthma, urticaria or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients. Voltaren Gel is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.


Voltaren Gel should not be used in combination with other oral NSAIDs or aspirin because of the potential for increased adverse effects. Similarly, combined use of Voltaren Gel with other topical products, such as sunscreens and cosmetics, on the same skin area has not been tested and should be avoided because of the potential to alter local tolerability and absorption.


About Endo


Endo Pharmaceuticals Holdings Inc. is a specialty pharmaceutical company with market leadership in pain management. Through its wholly owned Endo Pharmaceuticals Inc. subsidiary, the company is engaged in the research, development, sale and marketing of branded and generic prescription pharmaceuticals used primarily to treat and manage pain. More information, including this and past press releases of Endo Pharmaceuticals Holdings Inc., is available at endo.


Forward-Looking Statements


This press release contains information that includes or is based on "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, or the Securities Act, and Section 21E of the Securities Exchange Act of 1934, as amended, or the Exchange Act. These statements, including estimates of future net sales, future expenses, future net income and future earnings per share, are subject to risks and uncertainties. Forward-looking statements include the information concerning the company's possible or assumed results of operations. Also, statements including words such as "believes," "expects," "anticipates," "intends," "estimates," "plan," "will," "may" or similar expressions are forward-looking statements. Endo has based these forward-looking statements on its current expectations and projections about the growth of its business, its financial performance and the development of its industry. Because these statements reflect Endo's current views concerning future events, these forward-looking statements involve risks and uncertainties. Investors should note that many factors could affect Endo's future financial results and could cause its actual results to differ materially from those expressed in forward-looking statements contained in this press release. Important factors that could cause its actual results to differ materially from the expectations reflected in the forward-looking statements in this press release include, but are not limited to: its ability to successfully develop, commercialize and market new products; timing and results of pre-clinical or clinical trials on new products; its ability to obtain regulatory approval of any of its pipeline products; competition for the business of its branded and generic products, and in connection with its acquisition of rights to intellectual property assets; market acceptance of its future products; government regulation of the pharmaceutical industry; its dependence on a small number of products; its dependence on outside manufacturers for the manufacture of its products; its dependence on third parties to supply raw materials and to provide services for certain core aspects of its business; new regulatory action or lawsuits relating to its use of narcotics in most of its core products; its exposure to product liability claims and product recalls and the possibility that the company may not be able to adequately insure itself; its ability to protect its proprietary technology; the successful efforts of manufacturers of branded pharmaceuticals to use litigation and legislative and regulatory efforts to limit the use of generics and certain other products; its ability to successfully implement its acquisition and in-licensing strategy; regulatory or other limits on the availability of controlled substances that constitute the active ingredients of some of its products and products in development; the availability of third-party reimbursement for its products; the outcome of any pending or future litigation or claims by the government; its dependence on sales to a limited number of large pharmacy chains and wholesale drug distributors for a large portion of its total net sales; significant litigation expenses to defend or assert patent infringement claims; any interruption or failure by its suppliers, distributors and collaboration partners to meet their obligations pursuant to various agreements with Endo; a determination by a regulatory agency that Endo is engaging in inappropriate sales or marketing activities, including promoting the "off-label" use of its products; existing suppliers become unavailable or lose their regulatory status as an approved source, causing an inability to obtain required components, raw materials or products on a timely basis or at commercially reasonable prices; the loss of branded product exclusivity periods and related intellectual property; and its exposure to securities that are subject to market risk.


The company does not undertake any obligation to update its forward-looking statements after the date of this Report for any reason, even if new information becomes available or other events occur in the future. You are advised, however, to consult any further disclosures we make on related subjects in our 10-K, 10-Q and 8-K reports to the Securities and Exchange Commission (or SEC). Also note that Endo provides the preceding cautionary discussion of risks, uncertainties and possibly inaccurate assumptions relevant to its business. These are factors that, individually or in the aggregate, the company believes could cause its actual results to differ materially from expected and historical results. Endo notes these factors for investors as permitted by the Private Securities Litigation Reform Act of 1995. You should understand that it is not possible to predict or identify all such factors. Consequently, you should not consider the preceding to be a complete discussion of all potential risks or uncertainties.


References


[1] U.S. Centers for Disease Control and Prevention (CDC). Arthritis Related Statistics. Available here. Accessed on October 17, 2007.


[2] National Institute of Arthritis Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, U.S. Department of Health and Human Services. Handout on Health: Osteoarthritis. Available here. Accessed on October 17, 2007.


[3] Arthritis Foundation. Available at: arthritis. Accessed on October 17, 2007.


[4] U.S. Centers for Disease Control and Prevention (CDC). [CDC (2007) Update: National and State Medical Expenditures and Lost Earnings Attributable to Arthritis and Other Rheumatic Conditions-United States, 2003. MMWR Morb Mortal Wkly Rep, 56(01):4-7].

Endo Pharmaceuticals Inc.

Rheumatoid Arthritis Patients Have Double The Risk Of Heart Failure

Mayo Clinic researchers have found that rheumatoid arthritis patients have twice the risk of heart failure, or a
weakening of the heart's ability to pump blood, as those without rheumatoid arthritis, according to a new study to be
published in the February edition of the journal Arthritis & Rheumatism???.rheumatology. About one-third of the rheumatoid arthritis patients studied developed heart failure
over 30 years of the disease.


"We decided to undertake this study because we knew that patients with rheumatoid arthritis die earlier than the general
population, and mostly from heart disease," says Paulo Nicola, M.D., Mayo Clinic research fellow in the Department of Health
Sciences Research and study author. "We thought heart failure could be a reason for early mortality in these patients.
However, we were not expecting that the incidence of heart failure would be so high."


The study found that patients with rheumatoid arthritis are at an increased risk for heart failure soon after the onset of
arthritis and that this elevated risk follows them throughout the course of the arthritis, a chronic disease. The researchers
also found that the factors putting them at this increased risk for heart failure seem to be unrelated to heart attacks and
to the traditional cardiovascular risk factors: diabetes; alcohol abuse; and elevated cholesterol, blood pressure and body
mass index. The source of the increased risk remains a mystery, however.


"We expected heart attacks and traditional cardiac risk factors to contribute to the increased risk of heart failure in
rheumatoid arthritis patients, but they did not," says Dr. Nicola. "This suggests another mechanism is at work. We suspect
that it has something to do with the underlying inflammation that occurs in people with rheumatoid arthritis. Another
possibility is that patients with rheumatoid arthritis are particularly vulnerable to develop heart disease through a
mechanism that we don't yet understand. These observations may also suggest the potential presence of a common susceptibility
for developing rheumatoid arthritis or cardiac heart failure, or a shared origination of these diseases."


The study's researchers also noted little difference between rates of heart failure in men and women with rheumatoid
arthritis.


"This is quite different from what you'd find in the general population, where rates of heart failure are significantly
higher among men than in women," says Dr. Nicola. "This suggests that whatever protects women from heart failure compared
with men in the general population is not the same in patients with rheumatoid arthritis."















Heart failure is a serious disease, according to Dr. Nicola, causing a survival as short as most cancers. He indicates that
in the general population, about one-half of heart failure patients die within three to five years.


At present, the study investigators cannot prescribe preventive measures for rheumatoid arthritis patients to take in order
to avoid heart failure; they suggest that this is a subject for further study. The Mayo researchers also are conducting
studies to find out which rheumatoid arthritis patients are at highest risk for heart failure and to identify whether
arthritis medications are protective or contributors to heart failure.


In the meantime, Dr. Nicola says, "Patients with rheumatoid arthritis should be vigilant regarding reducing their traditional
cardiac risk factors. Their physicians should have a high degree of suspicion of heart failure -- for example, they should be
suspicious when rheumatoid arthritis patients relate that they are more tired than normal."


The Mayo Clinic study utilized the resources of the Rochester Epidemiology Project, mayoresearch.mayo/mayo/research/rep, which
allowed the researchers to study a broad spectrum of individuals from the Rochester, Minn., area with all ranges of
rheumatoid arthritis severity. The arthritis patients' experiences were measured against other study subjects who did not
have rheumatoid arthritis but who matched the arthritis patients in age and gender. The arthritis patients were initially
diagnosed between 1955 and 1995, and all individuals in the study were followed until death, heart failure, moving from
Rochester, or Jan. 1, 2001. The researchers found that rheumatoid arthritis increased an individual's risk of heart failure
1.9 times the risk of those without the disease.


This study's senior investigator is Sherine Gabriel, M.D., Mayo Clinic rheumatologist, epidemiologist and chair of the
Department of Health Sciences Research. Other Mayo Clinic study collaborators include: Hilal Maradit Kremers, M.D.; Veronique
Roger, M.D., Steven Jacobsen, M.D., Ph.D.; Cynthia Crowson; and Karla Ballman, Ph.D.


The paper detailing these findings is entitled, "The Risk of Congestive Heart Failure in Rheumatoid Arthritis: A
Population-Based Study Over 46 Years."


Note for reporters: As the subjects in which the present analysis was conducted 1) have no direct patient relationship with
the investigators and 2) participated in this study under strict confidentiality agreements, the participants are not
available for news media interviews. The lead investigator, Dr. Gabriel, is available to speak to news media.


To obtain the latest news releases from Mayo Clinic, go to mayoclinic/news. MayoClinic (mayoclinic) is available as a resource for your health stories.


Lisa Lucier - newsbureaumayo

Mayo Clinic

New Risk Gene For Rheumatoid Arthritis And Lupus Opens Door To More Effective Treatments

Scientists at The
Feinstein Institute for Medical Research have identified a critical gene
that increases a person's risk for rheumatoid arthritis and systemic lupus
erythematosus, and may be involved with other autoimmune diseases.


The genetic link, described in the September 6th issue of the New
England Journal of Medicine, was a collaborative effort led by Peter K.
Gregersen, MD, head of The Feinstein Institute's Robert S. Boas Center for
Genomics & Human Genetics. A decade ago, Dr. Gregersen helped bring
together scientists from a dozen institutes to pool patients and add
strength in numbers as they collectively hunt for genes. More recently, the
North American Rheumatoid Arthritis Consortium (NARAC) studied a region
identified on chromosome 2 in previous linkage studies conducted by the
same team. In the latest study, they analyzed DNA from 2,500 patients with
rheumatoid arthritis (RA) or lupus. Genetic mapping enabled them to
identify STAT4 as a culprit in susceptibility to both diseases.



"This work required the collection and genotyping of thousands of RA
and lupus patients and volunteers, a task that would have been difficult to
accomplish without the strong partnerships we forged," said Stephen I.
Katz, MD, PhD, director of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS). The federal institute has
supported NARAC since its inception.



"Identifying STAT4 as the relevant gene on chromosome 2 is very
exciting," added Elaine Remmers, PhD, a lead author in the NEJM study on
STAT4 and a staff scientist in the NIAMS's Genetics and Genomics Branch.
"We now are faced with trying to figure out how this variant of STAT4
increases a person's risk."



About 22 percent of people in the United States inherit this particular
form of STAT4. Having this variant of STAT4 confers a 30 percent increased
risk for developing rheumatoid arthritis. People with two copies of STAT4
have a 60 percent increased risk, Dr. Gregersen said. Rheumatoid arthritis
is a painful inflammatory condition of the joints. It is an autoimmune
disease, which means the body's immune system recognizes a product in the
lining of the joint as foreign and wages an attack. Patients with lupus,
also an autoimmune disease, have about double the risk compared to people
without this variant of STAT4.



In a companion study by Dr. Gregersen and his colleagues, STAT4 popped
up as an important risk gene in a population of patients in Korea. This
paper is published this month in Molecular Medicine.



One percent of people will develop rheumatoid arthritis. There are
probably dozens of genes, perhaps more, involved in triggering complex
diseases like rheumatoid arthritis.



"Identifying this risk gene is important because it points us in the
right direction," said Dr. Gregersen, who also just completed a whole
genome-wide association study of rheumatoid arthritis that will appear
later this month in the NEJM. The study is online as of September 6th with
an accompanying editorial. In this paper, the scientists identified another
risk gene -- TRAF1-C5.
















"The identification of these two new autoimmunity genes has profound
significance for our understanding of these complex diseases and our
ability to develop more specific diagnostic tests and therapies," said
Lindsey Criswell, MD, PhD, professor of medicine at UCSF and a
co-investigator on both studies.



A lot is known about the STAT4 gene and the protein it makes. STAT4 is
a signaling molecule that mediates the effects of immune system cytokines
such as IL12 and some types of interferon. STAT4 controls the
differentiation of T- cells into TH1 cells and may contribute to the
development of TH17 cells, both of which seem to have a role in maintaining
chronic inflammation in the body.



Inhibiting STAT4 can prevent or ameliorate arthritis in animal models
of rheumatoid arthritis, suggesting that STAT4 could be a target for new
therapies. The discovery of STAT4 can ultimately help scientists unravel
the triggers for the disease, help in the development of a test to confirm
a diagnosis and perhaps even help predict who will respond to treatments.



The NARAC and collaborators at Celera Diagnostics previously identified
PTPN22 as another risk gene in 2004. PTPN22 influences the "trigger point"
for activation of T-cells -- immune cells normally called on to wage battle
against infection. In autoimmune diseases like rheumatoid arthritis, PTPN22
appears to put people at higher risk of a wayward T-cell response. Dr.
Gregersen said that the two genes -- PTPN22 and STAT4 -- appear to work
independently to increase the risk for rheumatoid arthritis.



These are the first RA genes to be discovered since the 1980s when
scientists reported detailed association with genetic variants in the HLA
region known as the "shared epitope," work for which Dr. Gregersen is still
widely recognized. The key to the new genetic discoveries, Dr. Gregersen
said, is to have "more patients and controls. With higher numbers of
volunteers, we will have more power to pull out additional new genes and
figure out what they do in triggering these diseases. Continued
international collaboration with colleagues at the Karolinska Institute in
Stockholm will be critical for these efforts."



In addition to Drs. Gregersen, Criswell and Remmers, the NARAC
investigators on the STAT4 study include Christopher Amos, PhD, of The
University of Texas M.D. Anderson Cancer Center; Daniel Kastner MD, PhD, of
NIAMS's Genetics and Genomic Branch; Michael F. Seldin MD, PhD, of the
University of California, Davis; and Robert M. Plenge, MD, PhD, of the
Brigham and Women's Hospital. Timothy W. Behrens, MD, senior director of
immunology, tissue growth & repair at Genentech, Inc. was a key
collaborator on the lupus research.



The NARAC team is also part of the whole genome association study to be
published later this month in the NEJM. Other collaborators on this study
include Lars Klareskog of the Karolinska Institute; Mark Seielstad of the
Genome Institute of Singapore; and John Carulli, PhD, and Evan Beckman, MD,
of Biogen Idec in Cambridge, Ma.



Headquartered in Manhasset, NY, The Feinstein Institute for Medical
Research is home to international scientific leaders in Parkinson's
disease, Alzheimer's disease, psychiatric disorders, rheumatoid arthritis,
lupus, sepsis, inflammatory bowel disease, diabetes, human genetics,
leukemia, lymphoma, neuroimmunology, and medicinal chemistry. The Feinstein
Institute, part of the North Shore-LIJ Health System, ranks in the top 6th
percentile of all National Institutes of Health grants awarded to research
centers. Feinstein researchers are developing new drugs and drug targets,
and producing results where science meets the patient.


The Feinstein Institute for Medical Research

FeinsteinInstitute

ACZ885 Phase III Data Show Rapid, Sustained Clinical Remission In Children And Adults Suffering From A Group Of Rare Autoinflammatory Diseases

New Phase III data demonstrate that ACZ885 (canakinumab), a biological drug in development, achieved rapid and long-lasting clinical remission after just one dose in children and adults with a group of rare but potentially life-threatening autoinflammatory diseases called Cryopyrin-Associated Periodic Syndromes (CAPS)1. Due to the long duration of response, patients only needed further treatment every two months1.


In addition, preliminary results of a Phase I/II study in Systemic Juvenile Idiopathic Arthritis (SJIA), the most severe form of arthritis in children, showed that most patients treated with ACZ885 achieved substantial clinical improvement within 15 days2.


The data, presented at the American College of Rheumatology (ACR) meeting in San Francisco, confirm the potential of ACZ885 to fulfill an unmet medical need in the treatment of autoinflammatory diseases, which can cause life-long debilitating symptoms and potentially fatal complications3.


"The results for ACZ885 are exciting for patients and for the medical community," said Professor Philip Hawkins of the National Amyloidosis Centre at the Royal Free and University College Medical School, London. "Current treatments are not always effective, and are also short-acting and often poorly tolerated by patients. The rapid and long-lasting remission induced by ACZ885 is an important and much-needed development for both children and adults with CAPS."


The significant findings are based on the selective mechanism of action of ACZ885, a fully human monoclonal antibody. Unlike other agents, ACZ885 solely blocks interleukin-1?? (IL-1??), the form of the interleukin-1 protein that sustains autoinflammatory diseases such as CAPS.


CAPS, including Muckle-Wells Syndrome, are characterized by a single gene mutation that activates excessive production of IL-1??. This leads to symptoms such as fever, fatigue, skin rash, painful joints and muscles, and severe headache. In addition, patients can suffer from more debilitating complications like hearing loss and amyloidosis, which may lead to accumulations of amyloidosis (a protein) in kidneys causing dialysis or transplantation3.


IL-1?? is also thought to play a pivotal role in Systemic Juvenile Idiopathic Arthritis (SJIA)4, causing symptoms such as destructive arthritis, fever and rash. Suboptimal treatment can lead to growth retardation and joint and bone disability, as well as developmental and social consequences and life-threatening complications such as Macrophage Activated Syndrome, mostly caused by infections and requiring immediate intensive care4.















"Children and adults affected by these inflammatory diseases have to cope daily with very distressing and debilitating symptoms," said Trevor Mundel, MD, Head of Global Development Functions at Novartis Pharma AG. "We are extremely encouraged by these results that highlight the potential of ACZ885 to address the enormous unmet need in patients with these conditions."


The potential of ACZ885 is reflected in its broad development program. In addition to the studies in CAPS and SJIA, it is also being investigated in more common inflammatory diseases such as rheumatoid arthritis (RA), which affects up to 1% of the world's population5. Studies are currently under way in RA using an innovative tailored approach with biomarkers to predict response to treatment. If successful, these will give suitable patients a personalized approach to the treatment of their disease.


The six-month CAPS clinical trial presented at ACR involved patients aged nine to 74 years old and was divided into three parts. In the first part lasting two months, 35 patients received a single dose of ACZ885 by subcutaneous injection. All but one patient (97.1%) showed a rapid and long-lasting clinical and biochemical response1.


After this, 31 patients who maintained their response proceeded to part two, a randomized six-month, double-blind, placebo-controlled withdrawal design study. Patients were treated every two months and if a relapse occurred, they discontinued and entered part three1.


Part two of the study included the primary endpoint, a comparison between the number of patients treated every two months with ACZ885 who experienced disease outbreaks or 'flares' vs. those on placebo. Results showed that no patients in the ACZ885 group experienced a disease flare compared to 81% (13 out 15 patients) in the placebo group (p

Growing Cartilage From Stem Cells

Damaged knee joints might one day be repaired with cartilage grown from stem cells in a laboratory, based on research by Professor Kyriacos Athanasiou, chair of the UC Davis Department of Biomedical Engineering and his colleagues.



Using adult stem cells from bone marrow and skin as well as human embryonic stem cells, Athanasiou and his group have already grown cartilage tissue in the lab. Now they are experimenting with various chemical and mechanical stimuli to improve its properties.



Cartilage is one of the very rare tissues that lacks the ability to heal itself. When damaged by injury or osteoarthritis, the effects can be long-lasting and devastating.



"If I cut a tiny line on articular cartilage (the cartilage that covers the surfaces of bones at joints), it will never be erased," Athanasiou said. "It's like writing on the moon. If I go back to look at it a year later, it will look exactly the same."



Work that Athanasiou's group began in the early 1990s at Rice University has resulted in the only FDA-approved products for treatment of small lesions on articular cartilage. (In total, Athanaisou's patents have resulted in 15 FDA-approved products.)



"This will be live, biological cartilage that will not only fill defects, but will potentially be able to resurface the entire surface of joints that have been destroyed by osteoarthritis," Athanasiou said. Currently, joint replacements using metal and plastic prosthetics are the only recourse for the one in five adults who will suffer major joint damage from osteoarthritis.



Source:
Andy Fell


University of California - Davis

Novel Mouse Model Reveals Role Of Hyaluronic Acid In Skeletal Growth And Could Enhance Future Research

Investigators at Burnham Institute for Medical Research (Burnham) and the University of Connecticut Health Center (U.C.H.C.) have gained new understanding of the role hyaluronic acid (HA) plays in skeletal growth, chondrocyte maturation and joint formation in developing limbs. Significantly, these discoveries were made using a novel mouse model in which the production of HA is blocked in a tissue-specific manner. The Yamaguchi laboratory genetically modified the Has2 gene, which is a critical enzyme for HA synthesis, so that the gene can be "conditionally" disrupted in mice. This is the first time a conditional Has2 knockout mouse has been created, a breakthrough that opens vast possibilities for future research. The paper was published online in the journal Development on July 24.



HA is a large sugar molecule that is produced by every cell in the body and has been thought to play a role in joint disease, heart disease and invasive cancers. Yu Yamaguchi, M.D., Ph.D., a professor in the Sanford Children's Health Research Center at Burnham and Robert Kosher, Ph.D., a professor in the Center for Regenerative Medicine and Skeletal Development at U.C.H.C. and colleagues showed that transgenic mice, in which Has2 was inactivated in the limb bud mesoderm, had shortened limbs, abnormal growth plates and duplicated bones in the fingers and toes.



"Because hyaluronic acid is so prevalent in the body, it has been difficult to study," said Dr. Yamaguchi. "Systemic Has2 knockout mice died mid-gestation and could not be used to study the role of HA in adults. By inactivating Has2 in specific tissues, we give ourselves the opportunity to study the many roles HA plays in biology. This mouse model will be useful to study the role of HA in various age-related diseases and conditions, such as arthritis and skin aging, as well as cancer."



To create the conditional knockout mice, the Yamaguchi laboratory genetically engineered the Has2 gene to create the Has2flox allele. The team then added the Prxl1-Cre transgene, which is associated with early limb bud mesenchyme to produce the conditional Has2 knockout mice.



The research was funded by grants from the National Institutes of Health.



Source:
Josh Baxt


Burnham Institute

Long-Term Data Shows No Increase In Cancer Cases From Biologic Therapy

Data from one large U.S. registry indicate that biologic therapy does not appear to increase overall risks of cancers other than skin cancers in patients with rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Washington, DC.


Genetically-engineered biologic agents are often prescribed to counter abnormalities in the immune system that can cause joint inflammation. Typically, however, biologics such as adalimumab, etanercept, infliximab, anakinra and abatacept, are used only as a second line therapy because of their costs as well as possible side effects. Most significantly, concern centers on the perceived added risk for serious infections and cancers as biologic agents are used to treat rheumatoid arthritis.


To assess these possible risks, researchers studied 13,000 individuals participating in the National Data Bank of Rheumatic Disease between 1998 and 2005. Participants reported on all drug use, including biologics, as well as all cancers semi-annually. Of these, 48% had taken biologics. Those reporting new cases of non-melanotic skin cancer totaled 623, while 537 new cases were reported for other cancers.


Comparing these cases with the National Cancer Institute's SEER Database, which tracks cases across the general population, researchers found an increased risk for new melanoma and non-melanotic skin cancer cases in those using biologics. However, there were no significant differences in the risks for all other cancers in this population. Longer follow-up may be required to be certain of the non-association of biologic therapy and tumors other than skin cancers.


"These reports, which confirm registry data studies conducted in Europe, offer valid measurements of cancer rates in rheumatoid arthritis," explains Frederick Wolfe, MD, Project Director, National Data Bank for Rheumatic Disease, Wichita, Kansas, and an investigator in the study. "While longer follow-up may be required, this data shows the use of biologic therapy is not associated with increased risks of lymphoma, lung cancer or other cancers among those with rheumatoid arthritis."


The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see rheumatology/annual.















Presentation Number: 1321


The Association of New Cases of Cancer with Biologic Therapy


Frederick Wolfe, Kaleb Michaud. National Data Bank for Rheumatic Diseases, Wichita, KS


PURPOSE. Some studies of biologic therapy in randomized trials have suggested the possibility of an increase in lymphoma and/or lung cancer among persons with rheumatoid arthritis (RA) treated with biologics. Possible mechanisms include induction of lymphomas and acceleration of latent solid tumors. However, the number of cases in individual trials is small and confounded by differential severity. We used a longitudinal RA registry to compare biologic and non-biologic users with respect to cancer development.


METHODS. We studied incident cases of cancer among 13,001 subjects participating in a study of RA outcomes during 49,000 patient years of observation and 13 semiannual assessments in the years 1998-2005. Cancer reports were validated by hospital, physician and death records, except for non-melanotic skin cancer that was based on self-report and follow-up interview. Subjects were characterized as ever or never users of biologic therapy prior to the development of the cancer or the end of the follow-up period, and then further characterized by duration of individual biologic and total biologic use. Cancer rates were compared with overall population rates using the U.S. National Cancer Institute SEER data bank. Tests of treatment effect used conditional logistic regression to calculate odds ratios as estimates of the relative risk of the various cancers. In addition to conditioning on semiannual entry and exit period, we included six factors as an a priori set of confounders in all models. The included factors were age, sex, education level, smoking history, illness severity and prednisone use.


RESULTS. Biologic use was 48%. There were 623 incident cases of non-melanotic skin cancer and 537 other cancers. The standardized incidence rates (SIR) and 95% CI were: all cancers 1.0 (0.9-1.0), breast 0.7 (0.6-0.9), lung 1.1 (1.0-1.3), colon 0.5 (0.4-0.6), non-Hodgkin's lymphoma 1.6 (1.2-2.1). As shown in Table 1, biologic therapy was unassociated with major cancers, including lung cancer (odds ratio 1.1 (0.7-1.8)) and lymphoma (odds ratio 1.0 (0.5-2.0)). However, melanoma and other skin cancers occurred more frequently among biologic users including users of infliximab and etanercept.


CONCLUSIONS. This report confirms the results of European studies and shows an overall increase in lymphoma and lung cancer and decrease in breast and colon cancer in persons with RA, as well as non-increase when all cancers are considered simultaneously. Biologic therapy was associated with increased rate in melanotic and non-melanotic skin cancer, but not with any other form of cancer, including lymphoma and breast cancer. However, longer follow-up may be required to be certain of the non-association of biologic therapy and tumors other than skin cancers.


Disclosure Block: F. Wolfe, Research support from Amgen, Aventis, Bristol-Myers-Squibb, Centocor, 2; K. Michaud, None.


American College of Rheumatology (ACR)

1800 Century Place, Ste 250

Atlanta, GA 30345-4300

United States

rheumatology/

Rheumatoid Arthritis Patients Want Pain-Free Shopping Days At Christmas

A survey of women in the United Kingdom (U.K.) reveals that rheumatoid
arthritis (RA) has a severe emotional and physical impact on people living
with the disease and their families. Feelings of detachment and isolation
from those closest to them due to RA are especially prevalent at Christmas,
which should be one of the happiest times of the year. The survey findings of
300 women with RA living in the U.K. suggest that 33% feel the disease
impacts on their enjoyment of family events like Christmas, which increases
to 39% for women with moderate RA.





The survey, sponsored by biopharmaceutical company UCB, highlights that
more than a quarter (26%) of women with RA find it always more painful to
attend parties and celebrations or have stopped attending altogether; this
increases to 67% for women with severe RA. Additionally, RA is impacting on
personal relations, with more than a quarter of women believing the condition
affects their closest relationships for the worse, and 61% feeling that
friends and family do not understand their pain.





"Three quarters of UK women living with RA experience pain every day,
which can be more intense during busy times of the year, such as Christmas,
and this can seriously impact a patient's enjoyment of the festive season.
More than half of patients included in the survey are not talking to their
physician about pain control options, which is imperative to enable them to
take control of their pain, especially around Christmas when pain can be a
considerable issue. This will ensure that more patients achieve a pain free
'good day' and ultimately improve their quality of life." Said Professor Paul
Emery, Professor of Rheumatology, University of Leeds.





Pain is a huge issue for women living with RA in the U.K., as 76% of
respondents report experiencing pain daily. This can be exacerbated by the
dexterity needed for even the simplest of Christmas tasks which is
illuminated by the survey with 65% of severe RA respondents finding it
difficult to write Christmas cards.





Shopping for gifts, preparing food, writing cards and going to parties
are four festive activities that women living with RA in the U.K find most
difficult to do. Among women with severe RA, more than three quarters (78%)
experience difficulty when shopping for gifts, and 71% report it painful to
prepare Christmas food, with more than a quarter (27%) of these women having
stopped Christmas cooking altogether.





"So many women with RA in the UK have to live with the pain associated
with this debilitating disease, and the survey highlights that this is
particularly difficult to deal with during the Christmas period," said Ailsa
Bosworth, CEO of the National Rheumatoid Arthritis Society. "The pain
associated with RA is undertreated in the UK in our experience; we need to do
a better job of getting people's disease under control more rapidly to enable
people to enjoy more 'good days', particularly at this time of year."


















In light of the 'Good Days' survey findings, UCB and the National
Rheumatoid Arthritis Society have collaborated to develop the '12 Tips of
Christmas' with information to help people with RA manage and enjoy the
hectic holiday season. Please visit nras.uk/12Tips or email
12Tipsfleishman for the full guide that details ways to embrace and
enjoy the countdown to Christmas.





The U.K. survey findings are part of a global 'Good Days' survey which
evaluated the impact of RA on 1,958 women with RA from seven countries
worldwide. The survey findings suggest that women in the U.K. experience
greater difficulty and pain due to their condition than women living with RA
in the rest of the world. Whereas 76% of women in the U.K. experience pain
caused by their disease on a daily basis, on average only 63% of women
worldwide report daily pain from their RA. The global survey shows that the
feelings of isolation due to RA are universal and all women with RA report
that they conceal pain from family and friends, and worry about losing their
independence.





About the 'Good Days' Survey





The 'Good Days' Survey was conducted in August 2009 as part of a global
initiative assessing the lifestyles of women with rheumatoid arthritis in
seven major industrialized countries: Canada, France, Germany, Italy, Spain,
the United Kingdom and the United States. Objectives of the Survey included
identification of the physical and emotional impact of RA on day-to-day lives
of women living with the disease. A component of the Survey examined the
affects of the disease on people living with RA during the festive season.





Nearly 2,000 women aged between 25-65 years living with RA for six months
or more were interviewed online about the impact of the disease on their
lives. Of those interviewed in the 'Good Days' survey, 300 women with RA were
from the U.K.





About Rheumatoid Arthritis





It is estimated that 5 million people suffer from RA globally, with 0.8
percent of the U.K. adult population being affected. Prevalence is not split
evenly between genders, since women are three times more likely to be
affected than men3. Although RA can affect people of all ages, the onset of
the disease usually occurs between 30-50 years of age.





RA symptoms often lead to restricted mobility and permanent damage and
disfigurement of the joints and bones. People living with RA are at a higher
risk of developing other conditions, including heart disease, stroke,
depression, infections, lung problems and osteoporosis.






Source
UCB

Predicting The Risk Of Rheumatoid Arthritis For Early Arthritis Patients

Nine clinical variables help determine the need for early aggressive treatment



Marked by chronic inflammation of the joints and tissue, rheumatoid arthritis (RA) is a painful and potentially disabling autoimmune disease. A wealth of research supports early aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) as the best course for preventing joint damage and avoiding the fate of a wheelchair. Still, the use of DMARDs, even the widely prescribed and generally safe methotrexate, brings the risk of liver damage and other serious complications.



Among those who seek out a doctor's help for joint pain and stiffness, the most common diagnosis is undifferentiated arthritis (UA), or arthritic symptoms that do not add up to a specific arthritic disease. Spontaneous remission occurs in 40 to 50 percent of UA sufferers, while about one-third develop RA. Physicians often face the tough choice of whether to initiate DMARD therapy immediately or to wait and see. To guide individual treatment decisions, researchers with the Early Arthritis Clinic at Leiden University Medical Center, The Netherlands, have found a formula to help determine whether patients who present with UA are likely to progress to RA. The February 2007 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis) features their simple, reliable prediction rule for disease outcome.



Starting with clinical data for over 1,700 arthritis patients, the Leiden team identified 570 patients with recent-onset UA and monitored their disease for one year. At the culmination of follow-up, 177 of the original UA patients fulfilled the diagnostic criteria for RA and 150 had achieved remission; the remaining 94 had been diagnosed with another rheumatologic disease. Through a combination of questionnaires, physical examination, and blood samples, the team identified 9 clinical variables with independent predictive value for RA: sex, age, localization of symptoms, morning stiffness, the tender joint count, the swollen joint count, the C-reactive protein level, rheumatoid factor positivity, and the presence of anti-cyclic citrullinated peptide antibodies. Then, using the area under the curve (AUC), the diagnostic performance of the prediction rule was evaluated.



A prediction score, ranging from 0 to 14, was calculated for every patient in the group, with a higher score indicating a greater risk of developing RA. None of the patients who had a prediction score of less than 3 progressed to RA during the year-long observation. In contrast, all of the patients who had a prediction score of 11 or greater did experience progression to RA. Among the patients with scores between 4 and 10 who experienced progression to RA, the frequency of such progression increased with rising scores.



The percentage of patients in whom RA developed was also assessed according to several cutoff values of the prediction score. For example, when the scores 5.0 and 9.0 were chosen as cutoff values, 97 percent of patients with UA who had a score equal to or less than 5.0 did not develop RA, and a score of equal to or greater than 9.0 was associated with progression to RA in 84 percent of the patients.



"Because the prediction rule is accurate and can be easily determined in daily clinical practice, the present model is an important step forward in achieving individualized treatment in patients with recent-onset UA," notes team spokesperson Dr. Tom W. J. Huizinga. "Although the validation cohort is relatively small and the current prediction rule should be evaluated in other early-arthritis cohorts, we believe that the current model allows physicians and patients to make an evidence-based choice regarding whether or not to initiate DMARDs, in the majority of patients presenting with UA."







Article: "A Prediction Rule for Disease Outcome in Patients With Recent-Onset Undifferentiated Arthritis: How to Guide Individual Treatment Decisions," Annette H.M. van der Helm-van Mil, Saskia le Cessie, Henrike van Dongen, Ferdinand C. Breedveld, Rene E. M. Toes, and Tom W. J. Huizinga, Arthritis & Rheumatism, February 2007; (DOI: 10.1002/art.22380)



Contact: Amy Molnar


John Wiley & Sons, Inc.