Rheumatoid Arthritis Prevalence Is Lower Among Asians And Higher Among American Indians, Compared With Blacks And Whites In The U.S.

Decision Resources, one of the
world's leading research and advisory firms focusing on pharmaceutical and
healthcare issues, finds that in the U.S. rheumatoid arthritis prevalence
is lower among Asians and higher among American Indians, compared with the
prevalence among Blacks and Whites. The new analytics tool entitled
PatientFinder: Rheumatoid Arthritis also reveals that rheumatoid arthritis
prevalence in the U.S. varies by how urban or rural the population is.



"By applying these risk factors against U.S. population demographics
one might think that a state like Alaska, whose Native Alaskans have higher
rates of rheumatoid arthritis prevalence, might have a higher than average
percentage of patients," states Amanda Wilson, M.P.H., epidemiologist at
Decision Resources. "However, Alaska's rural population is much larger than
its Native Alaskan population, which actually drives overall prevalence of
the disease in this state below the national average."



In contrast, the new tool reveals that the Eastern Seaboard has seven
of the eight regions with the highest rheumatoid arthritis prevalence in
the U.S. -- Washington D.C., Pennsylvania, New Jersey, New York,
Connecticut, Rhode Island and Massachusetts -- due to high rates of
urbanization and low Asian populations.



Why Pharmaceutical Companies Need this Information



With the type of information included in PatientFinder, pharmaceutical
organizations can identify the local markets that offer the greatest
opportunity for their branded drug. Companies can identify markets that are
underserved and determine if they should increase direct-to-consumer
advertising, work with the local managed care organizations to increase
awareness of the disease and benefits of their drug or align sales
representatives to maximize market potential.



About PatientFinder



PatientFinder is the only healthcare analytics tool that assesses local
markets for expansion opportunity by determining the number of insured
patients in each territory who have the disease but are untreated.
PatientFinder covers each of the 50 U.S. states and 318 U.S. metropolitan
statistical areas (MSAs) and provides:


-- Disease-specific prevalence numbers for each U.S. state and MSA


-- Examination of treatment rates for the disease population to create
percent treated and percent untreated estimates by state and MSA


-- Unique analysis of the untreated population examined through a filter
of prescription (Rx) benefit coverage. The end result is an estimate of
how many patients are untreated but can afford therapy within each
territory -- the true local measure of opportunity for pharmaceutical
companies



About Decision Resources



Decision Resources (DecisionResources) is a world leader in
market research publications, advisory services and consulting designed to
help clients shape strategy, allocate resources and master their chosen
markets. Decision Resources is a Decision Resources, Inc. company.



About Decision Resources, Inc.



Decision Resources, Inc. is a cohesive portfolio of companies that
offers best-in-class, high-value information and insights on important
sectors of the healthcare industry. Clients rely on this analysis and data
to make informed decisions. Please visit Decision Resources, Inc. at
DecisionResourcesInc.



All company, brand or product names contained in this document may be
trademarks or registered trademarks of their respective holders.


Decision Resources

decisionresources

UCB's Meeting With U.S. FDA Defines Path Forward For Cimzia(R) In Rheumatoid Arthritis.

UCB announced that it met the U.S. Food and Drug Administration (FDA) and clarified the requirements for the approval of the Biologics License Application (BLA) for Cimzia®, the first PEGylated anti-TNF, for the treatment of rheumatoid arthritis (RA).



During the meeting, the FDA communicated that they require further analysis of existing data and a new safety update. No additional studies (clinical or non-clinical) are needed to fulfill this request.



"UCB is working diligently with the FDA to fulfil its request and, due to the already rich database available for Cimzia® in rheumatoid arthritis, we anticipate submitting the full response for Cimzia® in the second quarter of this year," said Prof. Dr. Iris Loew-Friedrich, Chief Medical Officer of UCB.



In January this year, UCB received a Complete Response Letter from the FDA in connection with the Cimzia® BLA. The BLA, accepted for filing and review in February 2008, was based on a clinical program conducted by UCB which included more than 2,300 patients, representing more than 4,000 patient years of experience and involved several multi-centre placebo-controlled Phase III trials.



On April 22, 2008, the FDA approved Cimzia® for reducing the signs and symptoms of Crohn's disease, and maintaining clinical response, in adult patients with moderate to severe active disease that have had an inadequate response to conventional therapy. Cimzia® is also approved in Switzerland for the induction of a clinical response, and for the maintenance of a clinical response and remission, in patients with active Crohn's disease who have not responded adequately to conventional treatment.



Cimzia® is also undergoing active review by the European authorities for the treatment of RA.




About Rheumatoid Arthritis


RA is a progressive autoimmune disease that causes chronic inflammation of the joints. It is estimated that five million people suffer from RA globally with 0.3 % to 1 % of the population in industrialized countries suffering from the disease. Women are three times more likely to be affected than men. Although it can affect people of all ages, the onset of RA usually occurs between the ages of 35-55.



Traditional treatments for RA include non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and disease-modifying antirheumatic drugs (DMARDs), with biological therapies a more recent addition.



About CIMZIA®


Cimzia® is the only PEGylated anti-TNF (Tumor Necrosis Factor). Cimzia® has a high affinity for human TNF-alpha, selectively neutralizing the pathophysiological effects of TNF-alpha. Over the past decade, TNF-alpha has emerged as a major target of basic research and clinical investigation. This cytokine plays a key role in mediating pathological inflammation, and excess TNF-alpha production has been directly implicated in a wide variety of diseases. The U.S. Food and Drug Administration (FDA) has approved Cimzia® for reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderate to severe active disease who have had an inadequate response to conventional therapy. Cimzia® was approved in Switzerland for induction of a clinical response and for the maintenance of a clinical response and remission in patients with active Crohn's disease who have not responded adequately to conventional treatment in September 2007. UCB is also developing Cimzia® in other autoimmune disease indications. Cimzia® is a registered trademark of UCB PHARMA S.A.
















About UCB


UCB, Brussels, Belgium is a biopharmaceutical company dedicated to the research, development and commercialization of innovative medicines with a focus in the fields of central nervous system and immunology disorders. Employing more than 10 000 people in over 40 countries, UCB aims to achieve revenues of at least EUR 3.3 billion in 2008. UCB is listed on Euronext Brussels (symbol: UCB).



Forward looking statement


This press release contains forward-looking statements based on current plans, estimates and beliefs of management. Such statements are subject to risks and uncertainties that may cause actual results to be materially different from those that may be implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include: changes in general economic, business and competitive conditions, effects of future judicial decisions, changes in regulation, exchange rate fluctuations and hiring and retention of its employees.


UCB


View drug information on Cimzia.

Golimumab Phase 3 Data Show Significant Improvement In Physical Function In Patients With Rheumatoid Arthritis

Results from two Phase 3 studies
showed that patients receiving every four week subcutaneous injections of
golimumab (CNTO 148) 50 mg or 100 mg, an investigational therapy,
experienced significant improvements in physical function, health-related
quality of life (HRQOL) and fatigue. The data from the randomized,
double-blind, placebo- controlled studies in patients with active moderate
to severe rheumatoid arthritis (RA) were presented at the American College
of Rheumatology (ACR) Annual Scientific Meeting. The first trial was in
patients who were previously treated with anti-tumor necrosis factor (TNF)
agents and the second study was in patients who were active despite ongoing
treatment with methotrexate.



"In addition to reducing signs and symptoms, these data show
improvement in important measures of functional ability and quality of
life," said Jonathan Kay, M.D., Director, Clinical Trials, Rheumatology
Unit, Massachusetts General Hospital; Associate Clinical Professor of
Medicine, Harvard Medical School, and lead study investigator. "These data
support the potential benefit of golimumab in patients previously treated
with anti-TNF therapies or methotrexate."



In the study, GOlimumab After Former anti-TNF Therapy Evaluated in RA
(GO-AFTER), 50 mg and 100 mg doses of golimumab were studied in patients
who had active RA and who were previously treated with anti-TNF treatments,
but where anti-TNF treatment had been discontinued due to lack of efficacy
(58 percent), intolerance (17 percent) or other reasons (40 percent).
Patients continued to receive stable doses of methotrexate, sulfasalazine
and/or hydroxychloroquine if they were receiving them at baseline.
Golimumab-treated patients who had discontinued previous anti-TNF treatment
for any reason experienced significant improvements in physical function,
as measured by the Health Assessment Questionnaire (HAQ). HAQ assesses the
degree of difficulty a person has in accomplishing tasks in eight
functional areas (dressing, arising, eating, walking, hygiene, reaching,
gripping and other activities of daily living).



At week 24, the proportion of patients experiencing clinically relevant
improvement (increase in HAQ score of at least 0.25 from baseline) was
significantly greater for golimumab-treated patients compared with those
receiving placebo. More than half of patients in the combined golimumab
group (52 percent) achieved the measure, compared with 34 percent of
placebo-treated patients (P < 0.001). Also at week 24, patients receiving
golimumab experienced a mean improvement in HAQ of 0.27 +/- 0.51, compared
with an improvement of 0.05 +/- 0.51 among patients receiving placebo (P <
0.001). Importantly, among patients whose prior anti-TNF therapy was
discontinued due to lack of efficacy, golimumab-treated patients
experienced a mean improvement of 0.23 +/- 0.50 in HAQ, compared with an
average improvement of 0.06 +/- 0.51 for patients receiving placebo (P <
0.05).
















At week 24, the combined golimumab group also experienced significantly
greater mean improvement in fatigue, 6.8 +/- 11.4, compared with an
improvement of 3.0 +/- 9.7 among patients treated with placebo (P < 0.001).
Patients were evaluated with the Functional Assessment of Chronic Illness
Therapy-Fatigue (FACIT-F), a 13-item questionnaire that assesses
self-reported fatigue and its impact on daily activities and function.



Improvements Seen in Patients Previously Treated with Methotrexate



A second Phase 3 study also presented at ACR evaluated 50 mg and 100 mg
doses of golimumab in RA patients who had active RA and were previously
treated with methotrexate. In GOlimumab FOR subjects With Active RA Despite
Methotrexate (GO-FORWARD), patients also indicated significant improvement
in fatigue. At week 24, the mean improvement in FACIT-F was 7.2 +/- 8.6 in
the combined golimumab group, compared with an improvement of 2.2 +/- 9.5
among patients receiving methotrexate alone (P < 0.001).



According to the Arthritis Foundation, in addition to joint pain and
swelling, RA may make daily functioning difficult and is frequently
associated with fatigue. "Patients with RA often say that fatigue is one of
their most frustrating symptoms because it makes it difficult for them to
participate in work or social activities," said Mark Genovese, M.D.,
professor of medicine at Stanford University School of Medicine, and lead
study investigator. "A reduction in fatigue would represent a tremendous
benefit and significantly impact the lives of patients with this disease."



Through week 24, patients in both dose groups receiving golimumab plus
methotrexate experienced significant improvement in physical function,
compared with patients receiving methotrexate alone. At 24 weeks, 70
percent of those receiving golimumab plus methotrexate experienced a
clinically relevant improvement in physical function, compared with 39
percent of patients receiving methotrexate alone (P < 0.0001). Also at week
24, the combined golimumab group achieved a mean improvement in HAQ of 0.46
+/- 0.53, compared with an improvement of 0.13 +/- 0.58 among patients
receiving methotrexate alone (P < 0.001).



Patients treated with golimumab also experienced significant
improvement in HRQOL, as assessed by the Physical Component Summary (PCS)
and Mental Component Summary (MCS) scores of the Short form (SF)-36
questionnaire. In the combined golimumab plus methotrexate group, the mean
improvement in PCS at week 14 was 7.7 +/- 8.1, compared with an improvement
of 2.5 +/- 8.1 in the group receiving methotrexate alone (P < 0.001).
Patients in the combined group also experienced a mean improvement in MCS
of 3.1 +/- 10.8 at week 24, compared with 0.8 +/- 9.7 among patients
receiving methotrexate alone (P < 0.05). The SF-36 is a 36-item
questionnaire that assesses impact in eight areas: physical functioning,
pain, vitality, social functioning, psychological functioning, general
health perceptions and role limitations due to physical and emotional
problems. Lower scores indicate poorer functioning and well- being.



The Biologics License Application (BLA) and Marketing Authorization
Application (MAA) for golimumab were submitted earlier in the year and are
currently under review by the U.S. Food and Drug Administration (FDA) and
European Medicines Agency (EMEA), respectively. The filings are based on
the extensive clinical development program for golimumab, including data
from five pivotal Phase 3 trials in RA, psoriatic arthritis and ankylosing
spondylitis.



About the GO-AFTER Trial



GO-AFTER was a Phase 3, multi-center, double-blind trial that included
461 patients with active RA of 8.65 years mean duration. All patients had
previously received at least one anti-TNF agent, with 25 percent (n=115)
having been treated with two therapies and 9 percent (n=43) with three.
Discontinuation of previous anti-TNF therapy was due to lack of efficacy
(58 percent), intolerance (17 percent) and other reasons (40 percent).
Patients were randomized to one of three treatment groups: subcutaneous
placebo, golimumab 50 mg or golimumab 100 mg every four weeks. At baseline,
66 percent of patients were receiving methotrexate; 5 percent and 7 percent
of patients were receiving sulfasalazine and hydroxychloroquine,
respectively. Patients continued to receive stable doses of methotrexate,
sulfasalazine and/or hydroxychloroquine if receiving them at baseline.



Golimumab was generally well tolerated in this study. Through week 24,
72 percent, 66 percent and 78 percent of patients in the placebo, golimumab
50 mg and golimumab 100 mg groups, respectively, experienced at least one
adverse event (AE). Ten percent of patients in the placebo group
experienced serious AEs, compared with 7 percent and 5 percent of patients
in the golimumab 50 mg and golimumab 100 mg groups, respectively. Serious
infections were reported in 3 percent, 3 percent and 1 percent of patients,
and injection site reactions (ISR) through week 16 occurred in 3 percent, 4
percent and 11 percent of patients in the placebo, golimumab 50 mg and
golimumab 100 mg groups, respectively. The most commonly reported ISR was
erythema, a redness of the skin due to inflammation. No serious or severe
ISRs were reported, and none led to the discontinuation of patients in the
study. Antibodies to golimumab were detected in 4 percent of
golimumab-treated patients (50 mg and 100 mg).



About the GO-FORWARD Trial



GO-FORWARD, a Phase 3, multi-center clinical trial included 444
patients with active RA. Adult patients with more than four tender and
swollen joints, despite methotrexate therapy, were randomly assigned to
receive golimumab (50 or 100 mg) plus methotrexate, golimumab 100 mg plus
placebo or placebo plus methotrexate at weeks 0, 4, 8, 12, 16 and 20. Data
were assessed at weeks 14 and 24. The co-primary endpoints were percentage
of patients achieving ACR 20 response at week 14 and improvement from
baseline in HAQ at week 24.



Through week 24, 68 percent of patients in both the combined golimumab
plus methotrexate groups and the placebo plus methotrexate group
experienced at least one AE. Nine percent of patients in the combined
golimumab plus methotrexate groups experienced a serious AE compared with 4
percent of patients receiving placebo plus methotrexate. Three percent of
patients in the combined golimumab plus methotrexate groups and 1 percent
in the group receiving placebo plus methotrexate experienced serious
infections. Rates of ISRs were 5 percent in the combined golimumab plus
methotrexate groups and 3 percent in the group receiving placebo plus
methotrexate. Two percent of golimumab-treated patients developed
antibodies. Four patients participating in the study developed
malignancies: one patient taking golimumab 100 mg plus methotrexate
developed breast cancer, one patient taking placebo plus methotrexate
developed Bowen's disease and squamous cell skin cancer, one patient taking
golimumab 100 mg plus placebo developed basal cell cancer, and one patient
taking golimumab 100 mg plus placebo developed squamous cell carcinoma. One
patient receiving golimumab 100 mg plus placebo died from diarrhea, colitis
and sepsis.



Anti-TNF therapies have been associated with serious and sometimes
fatal risks including the risk of tuberculosis and other serious
infections, malignancies, heart failure, central nervous system disorders,
reactivation of hepatitis B and other serious events.



About Rheumatoid Arthritis




RA is a chronic and debilitating disease that affects approximately 1.3
million people in the United States and more than three million people in
Europe. Signs and symptoms of RA include pain, stiffness and motion
restriction in multiple joints. Because RA is a progressive disease, it can
cause permanent joint deformity and severe disability if not diagnosed
early or if initial treatment is delayed. RA can occur at any age, but is
most common in adults 30-50 years old and is two-to-three times more
prevalent in women than in men. The cause of RA is unknown, although
genetic factors may contribute to the disease.



About Golimumab



Golimumab, the next-generation human anti-TNF-alpha monoclonal antibody
from Centocor Inc. and Schering-Plough Corporation, is currently in the
most comprehensive Phase 3 development program to date for an
anti-TNF-alpha biologic therapy. With ongoing studies for the treatment of
RA, including a study in a methotrexate-naive patient population, psoriatic
arthritis and ankylosing spondylitis, golimumab is being studied as an
every four-week subcutaneous injection and an intravenous (IV) infusion
therapy. Golimumab targets and neutralizes both the soluble and
membrane-bound forms of TNF- alpha.



Centocor discovered golimumab and has exclusive marketing rights to the
product in the United States. Pending regulatory approval, Schering-Plough
will assume exclusive marketing rights outside the United States except in
Japan, Indonesia and Taiwan where golimumab will be co-marketed by
Mitsubishi Tanabe Pharma Corporation and Janssen Pharmaceutical Kabushiki
Kaisha; Hong Kong, where golimumab will be exclusively marketed by
Janssen-Cilag; and China where golimumab will be exclusively marketed by
Xian-Janssen.



About Centocor



Centocor is harnessing the power of world-leading research and
biomanufacturing to deliver innovative biomedicines that transform
patients' lives. Centocor has already brought innovation to the treatment
of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic
arthritis, ulcerative colitis, pediatric Crohn's disease and psoriasis.



The world leader in monoclonal antibody production and technology,
Centocor has brought critical biologic therapies to patients suffering from
debilitating immune disorders. Centocor is a wholly-owned subsidiary of
Johnson & Johnson.



CENTOCOR DISCLOSURE NOTICE: This press release contains
"forward-looking statements" as defined in the Private Securities
Litigation Reform Act of 1995. These statements are based on current
expectations of future events. If underlying assumptions prove inaccurate
or unknown risks or uncertainties materialize, actual results could vary
materially from Centocor's expectations and projections. Risks and
uncertainties include general industry conditions and competition; economic
conditions, such as interest rate and currency exchange rate fluctuations;
technological advances and patents attained by competitors; challenges
inherent in new product development, including obtaining regulatory
approvals; domestic and foreign health care reforms and governmental laws
and regulations; and trends toward health care cost containment. A further
list and description of these risks, uncertainties and other factors can be
found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for
the fiscal year ended December 30, 2007. Copies of this Form 10-K, as well
as subsequent filings, are available online at sec, jnj or
on request from Johnson & Johnson. Centocor does not undertake to update
any forward-looking statements as a result of new information or future
events or developments.



About Schering-Plough



Schering-Plough is an innovation-driven, science-centered global health
care company. Through its own biopharmaceutical research and collaborations
with partners, Schering-Plough creates therapies that help save and improve
lives around the world. The company applies its research-and-development
platform to human prescription and consumer products as well as to animal
health products. Schering-Plough's vision is to "Earn Trust, Every Day"
with the doctors, patients, customers and other stakeholders served by its
colleagues around the world. The company is based in Kenilworth, N.J., and
its Web site is schering-plough.



SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press
release includes certain "forward-looking statements" within the meaning of
the Private Securities Litigation Reform Act of 1995, including statements
relating to the potential market for Golimumab. Forward-looking statements
relate to expectations or forecasts of future events. Schering-Plough does
not assume the obligation to update any forward-looking statement. Many
factors could cause actual results to differ materially from
Schering-Plough's forward-looking statements, including market forces,
economic factors, product availability, patent and other intellectual
property protection, current and future branded, generic or
over-the-counter competition, the regulatory process, and any developments
following regulatory approval, among other uncertainties. For further
details about these and other factors that may impact the forward-looking
statements, see Schering-Plough's Securities and Exchange Commission
filings, including Item 8.01 of Schering-Plough's Form 8-K filed October
21, 2008.


Centocor

centocor/centocor/index.html

Factors Causing Cartilage, Bone Destruction In Arthritis Suppressed By Green Tea Compound

In rheumatoid arthritis, a person's own immune system attacks the joints by activating the synovial tissue that lines the body's movable joints, causing inflammation, swelling, pain and eventually erosion of the bone and cartilage and deformation of the joint. It is among the most debilitating forms of arthritis, often making difficult even the simplest of daily activities.



In a study presented at Experimental Biology 2007, University of Michigan Medical School scientist Dr. Salah-uddin Ahmed reported that a compound derived from green tea was able to inhibit production of several immune system molecules involved in inflammation and joint damage. The compound, named epigallocatechin-3-gallate (EGCG), an active principal of green tea extract, is a potent anti-inflammatory molecule, and also was able to inhibit production of interleukin-6 (IL-6) and prostaglandin E2, the inflammatory products found in the connective tissue of people with rheumatoid arthritis.



Dr. Ahmed's Experimental Biology presentation was part of the scientific program of the American Society for Nutrition.



Synovial fibroblasts (cells that form a lining of synovial tissue surrounding the capsule of the joints) were isolated from the joints of the patients suffering from rheumatoid arthritis, cultured in growth medium, and incubated with EGCG. Synovial fibroblasts were then stimulated with pro-inflammatory cytokine IL-1??, a protein of the immune system known to play an important role in causing joint destruction in rheumatoid arthritis.



In an earlier study published by Dr. Ahmed's research group last fall, the researchers showed some interesting and novel findings when EGCG pretreated synovial fibroblasts were stimulated with the cytokine IL-1?? to study the protective effect of this green tea compound. Compared to untreated synovial fibroblasts, the cells treated with EGCG markedly blocked IL-1??'s ability to produce the proteins and enzymes that infiltrate the joints of persons with rheumatoid arthritis causing cartilage degradation.



The scientists decided to extend their study to see if the green tea compound also has the capability to block the activity of two other potent molecules, IL-6 and cyclooxygenase-2 (COX-2), actively involved in causing bone erosion in the RA joint. In the new study presented at Experimental Biology, the scientists once again isolated synovial fibroblasts taken from the joints of patients suffering from rheumatoid arthritis and incubated these cells with the green tea compound. When untreated cells were stimulated with IL-1??, a sequence of molecular events occurred that resulted in production of the bone-destructive molecules. But the scientists found that pre-incubation with EGCG was capable of blocking the production of these molecules in a dose-dependent manner. Furthermore, EGCG also inhibited the production of prostaglandin E2, which causes inflammation in the joints.



The cell signaling pathways that regulate levels of these immune system molecules under both normal and rheumatoid arthritis situations is well established, and the researchers were able to trace the effects of the green tea compound infusion to see that it worked by inhibiting these pathways.



Dr. Ahmed says that these studies suggest that EGCG or molecules that could be derived synthetically from the EGCG found in green tea may be of therapeutic value in inhibiting the joint destruction in this challenging disease. The laboratory now is focused on the inhibitory role of EGCG in gene expression. The scientists plan to give EGCG orally to mice genetically bred to be animal models of rheumatoid arthritis to see if it provides similar therapeutic or preventive effects. Dr. Ahmed believes these studies will form a strong foundation for future testing of green tea compounds in humans with rheumatoid arthritis.






Co-authors of the study are Dr. Angela Pakozdi and Dr. Alisa Koch of the University of Michigan and the Veterans Affairs Medical Center in Ann Arbor.



This research was supported by NIH grants and Veteran Administration Medical Research Service funds to Dr. Alisa Koch.



Contact: Sylvia Wrobel


Federation of American Societies for Experimental Biology

Orthopedic Researchers Study Knee Injuries And Degeneration

The sort of swelling that occurs when a joint is damaged by injury or degeneration is normally essential to the healing process, but when it comes to the knee, that inflammation can actually interfere with healing.



These findings in experiments with pigs may lead to treatments for injuries or osteoarthritis in the knee, according to Duke University Medical Center orthopedic researchers. There are drugs that can block the action of these immune system proteins that trigger joint inflammation.



The Duke researchers report in the September issue of the journal Arthritis & Rheumatism that two immune system proteins, interleukin-1 (IL-1) and tumor necrosis factor (TNF), block the healing of the damaged pig meniscus, an important layer of buffering tissue within the joint. When agents that counteract the effects of these two proteins were administered directly to the damaged meniscus, the repair process resumed.



The primary function of the meniscus -- a type of cartilage located within the knee joint between the thigh bone (femur) and the lower leg bone (tibia) -- is to act as a shock absorber and a distributor of weight within the joint. Nearly 15 percent of all athletic injuries to the knee involve the meniscus, and the breakdown and loss of this tissue ultimately leads to osteoarthritis, the so-called "wear-and-tear" form of the disease.



The researchers, led by Duke postdoctoral fellow Amy McNulty, Ph.D., said there is a need for a new approach to treat these injuries. The most common meniscus injury is a tear. If the tear is small and occurs on the outside of the meniscus, it can be repaired surgically. However, these repairs don't often work well. If the tear is large, surgeons often have no choice but to remove the torn portion, and sometimes the entire meniscus, which leads to painful movement and ultimately osteoarthritis.



Duke researchers exposed pig knees to various concentrations of IL-1 and TNF. They found that as they increased the amounts of the proteins, the meniscus tissue was less able to repair itself. The range of concentrations of IL-1 and TNF used in the experiment match those found in the joint fluid of humans with rheumatoid arthritis and osteoarthritis, providing further evidence that these proteins could play a role in the disease process.



According to Farshid Guilak, Ph.D., senior member of the research team and director of orthopedic research at Duke, these findings should theoretically help physicians repair knee joints damaged by injury or osteoarthritis.



"There already is a drug that blocks the effects of TNF that is used widely and effectively in patients with rheumatoid arthritis, the form of the disease caused by body's own immune system attacking the joint," Guilak said. "Another drug also exists that blocks IL-1 that is being used for rheumatoid arthritis and is currently undergoing clinical trials for osteoarthritis."



These drugs are administered to the entire body. However, the key to the possible new approach would be to deliver these agents directly into the site of meniscus damage, Guilak said.







The research was funded by the V.A. Research Service, the National Institutes of Health and the Arthritis Foundation, which is sponsoring McNulty's research. Duke's Frank Moutos and J. Brice Weinberg were also members of the team.



Source: Richard Merritt


Duke University Medical Center

News From The March 2008 Journal Of The American Dietetic Association

The March 2008 issue of the Journal of the American Dietetic Association contains articles and research studies you may find of interest. Below is a summary of some of this month's articles.



How Do Dietary Guides Match Up?



Since advice about what to eat for optimal health has evolved over time with advances in nutrition science, dietary recommendations are sometimes seen as contradictory. However, a review of three leading dietary guides by researchers at the National Cancer Institute found their essential recommendations are consistent despite the different methodologies used to create the guides.



The NCI researchers compared recommendations and nutrient values of the United States Department of Agriculture's MyPyramid; the National Heart, Lung and Blood Institute's DASH Eating Plan and Harvard's Healthy Eating Pyramid. The study showed that, even though the guides were derived from different types of nutrition research, they share consistent messages: Eat more fruits, vegetables, legumes and whole grains; eat less added sugar and saturated fat; and emphasize plant oils.



Recommendations are similar regarding almost all food groups for both types and amounts of foods people should eat. Primary differences were seen in the types of recommended vegetables and protein sources and the amount of recommended dairy products and total oil. Overall nutrient values were also similar for most nutrients, except vitamin A, vitamin E and calcium.



The researchers conclude: "The evidence base for optimal diets continues to evolve. However, inherent in these guides is a pattern of eating that focuses on nutrient-rich foods and limited calories from added sugar and solid fat."



Connections between Chronic Disease and Supplement Use



With cancer survivors increasingly turning to complementary and alternative medicine to manage the short-term and long-term effects of their conditions, a study from the National Cancer Institute concludes that having a chronic medical condition such as cancer is the primary factor in a person's decision to use dietary supplements.



The researchers studied records of more than 9,000 people. They found adults with cancer or other chronic conditions were more likely to use supplements than people reporting no illness.



According to the researchers, cancer was most closely associated with use of vitamins, while people living with other chronic conditions tended to use a wide variety of supplements.



"A diagnosis of cancer by itself does not have an independent effect on supplement use," the researchers write, adding that most supplement use among cancer survivors appears intended to prevent or lessen related conditions.



The researchers conclude: "These results indicate that having a chronic medical condition is the major factor associated with supplement use??¦. Consumers and health professionals should be aware that there is limited information on the effects of dietary supplements taken concurrently with prescription and other over-the-counter medications."
















Additional research articles in the March Journal of the American Dietetic Association include:



* Using Biomarker Data to Adjust Estimates of the Distribution of Usual Intakes for Misreporting: Application to Energy Intake in the U.S. Population



* Elevated Plasma Homocysteine and Low Vitamin B6 Status in Non-Supplementing Older Women with Rheumatoid Arthritis



* Relative Validity of the Iowa Fluoride Study Dietary Questionnaire and the Block's Kids' Food Questionnaire for Estimating Beverage, Calcium and Vitamin D Intakes by Children



* Country of Birth and Language Are Uniquely Associated with Intakes of Fat, Fiber and Fruits and Vegetables among Mexican-American Women in the United States



* Complementary and Alternative Medicine and the Management of the Metabolic Syndrome



* Probiotics and Prebiotics in Dietetic Practice.







The Journal of the American Dietetic Association is the official research publication of the American Dietetic Association and is the premier peer-reviewed journal in the field of nutrition and dietetics.



With more than 67,000 members the American Dietetic Association is the nation's largest organization of food and nutrition professionals. ADA serves the public by promoting optimal nutrition, health and well-being. To locate a registered dietitian in your area, visit the American Dietetic Association at eatright/.



Source: Jennifer Starkey


American Dietetic Association

Lower Levels Of Anti-inflammatory Proteins May Contribute To Chronic Widespread Pain

Chronic widespread pain, a common medical condition, can be difficult to treat and is often associated with fatigue, poor sleep and depression. A connection between fibromayalgia (FM) and cytokines (proteins that act as messengers between cells) was suspected after cancer patients treated with the cytokine interleukin -2 developed FM-like symptoms. Since then, other studies have shown contradictory results. A new study published in the August 2006 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis) examined cytokine profiles in patients with chronic widespread pain and found that they had significantly lower levels of the anti-inflammatory cytokines IL-4 and IL-10.



Led by Nurcan Uceyler of Julius-Maximilians University in Wurzburg, Germany, researchers analyzed cytokines in 40 patients with chronic widespread pain (26 of whom had FM), 40 controls and an additional group of 15 patients. The 40 pain patients had received intravenous immunoglobulin (IVIG) as a novel treatment for pain that was not responsive to standard therapy, while the additional 15 patients did not receive this treatment. Blood samples were analyzed for both pro-inflammatory and anti-inflammatory cytokines. In addition, patients were asked to rate their pain, fatigue, mood, cognitive function and sleep quality on a scale of 1 to 10.



Patients in the pain group did not differ in the expression of the pro-inflammatory cytokines IL-2, IL-8 and TNFα, but did have significantly lower levels of the anti-inflammatory cytokines IL-4 and IL-10 compared with the healthy control group. The 15 patients in the additional group showed similar findings, although the difference in IL-10 between this group and the controls was not statistically significant.



The authors point out that there may be several factors involved in the cause of low cytokine levels and how they might be linked to pain. Previous studies have shown that IL-10, administered as a protein or via gene transfer, reduces sensitivity to pain. Similarly, IL-4 has been shown to dull the pain response. "Signals arising through physiologic stimulation of the opioid receptor system may be reduced in patients with low IL-4 levels with subsequent increase in pain perception and the common relative opioid resistance seen in patients with chronic widespread pain," the authors note. In addition, genetic variations in different cytokine genes are associated with distinct diseases, such as the association between IL-4 gene variations and asthma, Crohn's disease, and chronic polyarthritis. "The low levels of IL-4 and IL-10 we observed in the patients with chronic widespread pain might therefore also be caused by genetic alterations either in the cytokine genes themselves or in regulatory elements, although other factors may be involved," the authors state.



The authors acknowledge that this study on 6 key cytokines does not exclude the possibility that other cytokines may play a role in chronic widespread pain. While they acknowledge that low levels of anti-inflammatory cytokines may be a consequence of chronic widespread pain and its treatment, they favor the hypothesis that these proteins actually play a role in the pathophysiology of chronic widespread pain. "Once confirmed and validated in further studies," they conclude, "cytokine expression patterns may eventually help in supporting the diagnosis of chronic widespread pain and in guiding the appropriate treatment approach."







Article: "Reduced Levels of Antiinflammatory Cytokines in Patients With Chronic Widespread Pain," Nurcan Uceyler, Regine Valenza, Michael Stock, Robert Schedel, G?nter Sprotte, Claudia Sommer, Arthritis & Rheumatism, August 2006; (DOI: 10.1002/art.22026).



Contact: Amy Molnar

John Wiley & Sons, Inc.

NICE Draft Guidance Set To Help People With Rheumatoid Arthritis

Final draft guidance published today (Thursday 21st January 2010) by the National Institute for Health and Clinical Excellence (NICE) will enable another therapy to be considered for some people in England, Wales and Northern Ireland suffering with rheumatoid arthritis.


In the draft, certolizumab pegol is now recommended as a treatment option for some patients with the disease.


Rheumatoid arthritis (RA) is a long-term disease in which joints in the body become inflamed, causing pain, swelling and stiffness. It often affects the small joints of the hands and the feet, and usually both sides equally and symmetrically. Around 400,000 people in the UK have RA and people of all ages can develop the disease. Over twice as many women as men suffer from the condition.


Certolizumab pegol is a type of treatment known as a TNF (tumour necrosis factor) inhibitor. It is recommended for the same use as the other TNF inhibitors: adalimumab, etanercept and infliximab, as outlined in existing NICE technology appraisal guidance 130.


This draft recommendation has been made possible after the manufacturer, UCB Pharma, supplied more detailed information on the clinical and cost effectiveness of its treatment, certolizumab pegol, for the treatment of RA. In the first draft guidance for certolizumab pegol (published in October 2009), the Appraisal Committee was minded not to recommend the drug unless additional information could be provided for their consideration.


The manufacturer (UCB Pharma) will also provide the first 12 weeks of certolizumab pegol free to all patients starting treatment through a patient access scheme agreed with the Department of Health.. Under the scheme, people will receive these first 12 weeks of therapy (currently 10 pre-loaded syringes of 200 mg each) of certolizumab pegol free of charge.


In line with the NICE technology appraisals process, this final draft of the guidance is now with consultees who have the opportunity to appeal against the proposed recommendation. NICE has not yet issued final guidance to the NHS.


Dr Carole Longson, Director, Health Technology Evaluation Centre said: "Rheumatoid arthritis can be extremely painful and therefore, very debilitating, not only for the thousands of people in the UK with the disease, but also their families and carers. I am pleased that, having considered the further information we requested, the independent Appraisal Committee has been able to make a positive draft recommendation for certolizumab pegol to be a treatment option for some patients."

Source
NICE

Pioneering Bristol Academic Raises $2.3 Million Investment For 'Cell Bandage'

A company co-founded by Professor Anthony Hollander, an academic from the University of Bristol, has raised over ??1.6 million to fund trials, including the first human study, of its pioneering 'cell bandage' technology, which aims to save thousands of patients from the type of knee surgery that currently leads to premature osteoarthritis.



Professor Hollander came to national prominence as part of the academic team that saved the life of Claudia Castillio, after developing the first tissue-engineered trachea (windpipe) using the patient's own stem cells. This fully functioning airway was transplanted into the patient and saved her life.



Azellon is now developing the first commercially practical applications of that same fundamental technology to create 'cell bandages' that can be transplanted into a damaged knee meniscus, helping to regenerate the joint, and saving the patient from future surgery and potentially debilitating osteoarthritis.



Azellon will develop a 'cell bandage' grown from the patient's own stem cells, and transplant it in the patient's knee joint within three weeks of extracting the stem cells from bone marrow.



The technology is believed to be the world's first adult and autologous (patient's own) stem cell treatment of meniscal tears. More than 1.7 million people globally are estimated to have a part of or the full meniscus removed per annum making it a common orthopaedic procedure. Partial or full removal of the meniscus (menisectomy) can provide significant pain relief within 3-5 months in most patients. It is, however, also well documented that 4-6 years after menisectomy, osteoarthritic changes are noticeable in the knee of many patients, often leading to further joint surgery including total knee replacement.



Company co-founder and Managing Director Troels Jordansen said:



'Azellon's technology is unique and has the potential to change the long term clinical outcome for thousands of patients who have parts of or the full meniscus removed with dire long term outcome. A unique element of the Azellon technology is that no tissue will be removed.'



Olympic swimmer Sharron Davies, MBE, a past sufferer of a torn meniscus agrees:



'If a stem cell treatment had been available for my injury, I might not have suffered the pain and discomfort that has become steadily worse over the past few years. As an athlete I am very excited about the possibility of this common sporting injury being healed with the patient's own stem cells.'



Azellon has raised the money from a consortium of funders that includes the Wellcome Trust, the Technology Strategy Board, IP Group, the Wyvern Fund, Oxford Technology Management and the Universities of Bristol and Bath.



The ??1.6 million raised will be invested in 3 pre-clinical trials covering safety, bio-distribution and cell fate, which will be carried out by University College London (UCL). In 2010 Azellon will initiate a human pilot study in Bristol.



'The cell bandage is a rare example of fundamental university research being developed for the benefit of patients,' said Azellon Chief Scientific Officer Professor Anthony Hollander.



'We are grateful not only to our investors, but to the funders of our research programme. The possibilities for tissue engineering from adult stem cells are enormous, and the University of Bristol is one of the world leaders in this field.'



Source:
Dara O'Hare


University of Bristol

Women Are Not Only More Predisposed To RA, The Disease May Also Be More Aggressive Compared To Men

Dr Bjorn Svensson, Rheumatology, University of Lund, Sweden, will today present a study which shows significant differences in the remission rates between women and men diagnosed with rheumatoid arthritis (RA).



Remission means a condition with little or no evidence of ongoing disease and as there is no cure to rheumatoid arthritis, this is currently the treatment goal of the disease. Dr Svensson and his research team analyzed the frequencies and predictors of remission in a large patient group observed for five years in a structured follow-up programme. During the period September 1995 to September 1999, 689 patients were included in a multicentre follow-up programme for patients with recent onset RA (disease duration < 1 year). The frequency of remission was studied after 2 and 5 years respectively.



In patients overall, 37.9% were in remission after the 2-year follow-up, while 38.5% were in remission after 5 years. However, only 32% and 31% of the women were in remission at 2 and 5 years respectively, versus 49% and 52% of the men.



Importantly, the female group in the study did not have explicitly different disease activity at treatment start compared to the male group. The results could not be explained by different treatment approaches as DMARDs and glucocorticoids were given similarly and as early to women as to men. Nor did patients age influence since the younger women and men were in remission as often as the older.



The causes of rheumatoid arthritis are unknown, but are predicted to be rather complex. However some of the factors that might play a role in the development of the disease are infections, genetics and gender, as shown in this study.



"The study showed that the disease course of the women examined was considerably worse than for the men. The reason for this gender discrepancy found in this study are at present unclear and will need further investigations", said Dr Svensson. "However, the data seems solid enough to call for reinforced attention in the frequency and quality of follow-up in order to achieve an optimal suppression of the inflammatory process in all patients, regardless of gender", he added.







For further information on this study, or to request an interview with the study lead, please do not hesitate to contact the EULAR congress press office on:



Email: eularpressofficeuk.cohnwolfe



Jim Baxter

Jo Spadaccino

Mia Gannedahl



Abstract number: OP0098



About EULAR



* The European League Against Rheumatism (EULAR) is the organization which represents the patient, health professional and scientific societies of rheumatology of all the European nations.

* The aims of EULAR are to reduce the burden of rheumatic diseases on the individual and society and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with musculoskeletal diseases by the governing bodies in Europe.

* Diseases of bones and joints, such as rheumatoid arthritis and osteoarthritis cause disability in 4 - 5 % of the adult population and are predicted to rise as people live longer.

* As new treatments emerge and cellular mechanisms are discovered, the 7th Annual European Congress of Rheumatology in Amsterdam (EULAR 2006) brings together more than 10,000 experts - scientists, clinicians, healthcare workers, pharmaceutical companies and patients - to share their knowledge in a global endeavour to challenge the pain and disability caused by musculo-skeletal disorders.

* To find out more information about the activities of EULAR, visit: eular/



Contact: Mia Gannedahl



European League Against Rheumatism

NicOx Completes Enrollment In Second Pivotal Phase 3 Study For Naproxcinod And Provides Development Update

NicOx S.A.
(Eurolist: COX) announced it has successfully completed the
enrollment of 1020 patients in the 302 pivotal phase 3 study for
naproxcinod, in-line with projections. Naproxcinod is the Company's lead
investigational drug product and the first compound in the COX-Inhibiting
Nitric Oxide-Donating (CINOD) class. The 302 study is designed to assess
naproxcinod's efficacy for treating the signs and symptoms of
osteoarthritis and provide additional blood pressure data, which is a key
factor for differentiating naproxcinod from existing anti-inflammatory
treatments. Efficacy results from this study are anticipated in the third
quarter of 2008.


The 302 study represents the largest of the three pivotal phase 3
trials for naproxcinod (the 301, 302 and 303 studies). The 301 study is
complete and results were recently presented at the 71st annual meeting of
the American College of Rheumatology (ACR), which showed that naproxcinod
met all three co-primary efficacy endpoints and demonstrated a similar
effect on systolic blood pressure to placebo and a reduction compared to
naproxen, a commonly used anti-inflammatory agent. The third and final
study (303) is a 13-week trial in patients with osteoarthritis of the hip.
Patient enrollment in this trial is well underway, following its initiation
in June 2007. Current timelines are that the 303 study should complete
enrollment in the second quarter of 2008, with results expected by the end
of 2008. NicOx now anticipates the filing of a New Drug Application (NDA)
for naproxcinod with the US Food and Drug Administration (FDA) in mid-2009.




"The 302 study is the largest and longest duration trial in our program
for naproxcinod and our clinical team has proved its effectiveness in
successfully recruiting the targeted number of patients in-line with
projected timelines," said Pascal Pfister, Chief Scientific Officer of
NicOx. "The 302 study will provide 13 and 26-week efficacy results and
supportive safety data for the regulatory filing of naproxcinod, in
addition to blood pressure data to aid its market differentiation. The
completion of patient enrollment in the 303 study is now a top priority and
together with the contract research organization for this trial, Covance
Inc., we have taken the step of opening additional clinical centers in
Europe to accelerate the recruitment in this study."



302 study design



The 302 study for naproxcinod was initiated in April, 2007 and is being
conducted by Premier Research Group plc. This study is a 53-week,
randomized, double-blind, efficacy and safety trial in which 1020 patients
with osteoarthritis of the knee have been enrolled at 150 clinical sites
throughout the United States. Patients have been randomized to one of the
following treatment groups: naproxcinod 375 mg bid (52 weeks), naproxcinod
750 mg bid (52 weeks), naproxen 500 mg bid (52 weeks) and placebo bid
during the first 13 weeks. After 13 weeks, the placebo treated patients are
being randomized to either naproxcinod 375 mg bid or naproxcinod 750 mg bid
for the remainder of the trial (39 weeks). Patients have primary
osteoarthritis of the knee of at least 3 months duration. The trial has
recruited both hypertensive and non-hypertensive patients, although
patients with uncontrolled hypertension have been excluded.
















The two doses of naproxcinod (750 mg and 375 mg bid) will be compared
to placebo on three co-primary efficacy endpoints, based on the mean change
between baseline and week-13 in the following scores: the WOMAC(TM) pain
subscale, the WOMAC(TM) function subscale and subject's overall rating of
disease status. These are the standard endpoints used to demonstrate the
efficacy of drugs for treating the signs and symptoms of osteoarthritis and
are the same as those used in the other two pivotal phase 3 studies for
naproxcinod. A secondary endpoint of the trial is to compare the efficacy
of naproxcinod and naproxen at 26 weeks. The general safety and
tolerability of naproxcinod are assessed until week-52 and the trial has a
1-week post-treatment safety period.



Patients' blood pressure is being assessed during each visit to the
treatment center, using controlled Office Blood Pressure Measurements
(OBPM). The blood pressure effect of naproxcinod will be assessed in the
overall population and a sub-group of hypertensive subjects. Various
secondary endpoints will compare the different treatments in terms of the
mean change from baseline in systolic and diastolic blood pressure, at a
range of time points. Additional secondary endpoints will assess the
appearance of new hypertension or worsening of pre-existing hypertension.



NicOx (Bloomberg: COX:FP, Reuters: NCOX.PA) is a product-driven
biopharmaceutical company dedicated to the development of nitric
oxide-donating drugs to meet unmet medical needs. NicOx is targeting the
therapeutic areas of inflammation and cardio-metabolic disease. Resources
are focused on two lead compounds, naproxcinod (formerly HCT 3012); in
phase 3 development for the treatment of signs and symptoms of
osteoarthritis, and NCX 4016, in phase 2 for type 2 diabetes.



NicOx has strategic partnerships with some of the world's leading
pharmaceutical companies, including Pfizer Inc and Merck & Co., Inc.



NicOx S.A. is headquartered in Sophia-Antipolis, France, and is a
public company listed on the Eurolist of Euronext(TM) Paris (segment: Next
Economy).



This press release contains certain forward-looking statements.
Although the Company believes its expectations are based on reasonable
assumptions, these forward-looking statements are subject to numerous risks
and uncertainties, which could cause actual results to differ materially
from those anticipated in the forward-looking statements.



For a discussion of risks and uncertainties which could cause actual
results, financial condition, performance or achievements of NicOx SA to
differ from those contained in the forward-looking statements, please refer
to the Risk Factors ("Facteurs de Risque") section of the document de
reference filed with the AMF, which is available on the AMF website
(amf-france) or on NicOx S.A.'s website
(nicox).


NicOx S.A.

nicox

63 Percent Of RA Patients Suffer Psychiatric Disorders, With Depressive Spectrum Conditions Most Likely

Over half (63%) of patients with rheumatoid arthritis (RA) also suffer from psychiatric disorders, with the majority of these (87%) occurring in the depressive spectrum, according to the results of a new study presented recently at EULAR 2009, the Annual Congress of the European League Against Rheumatism in Copenhagen, Denmark. Interestingly, over half (52%) of the patients studied indicated that they had experienced stress events before the onset of their RA.



The study also revealed a number of other interesting findings about the emotional burden of RA:



* Cognitive dysfunction was diagnosed in 23% of patients, with 16% of this attributed to depression


* A third (33%) suffered from sleep disorders


* Those with depression also exhibited more severe RA (measured by X-ray), greater functional insufficiency and pain, as well as having received less aggressive treatment than patients without depression. (No significant differences in age, duration of illness, gender or DAS28* scores were noted between the two groups)


* Significantly, cognitive impairments were found more often (p=0.02) in patients older than 50 years (39% vs. 9%)


* The age of the first prednisone intake was significantly higher (p

Arthritis May Be Treated With Umbilical Cord Cells

Umbilical cord stem cells may be useful in the treatment of rheumatoid arthritis (RA). Animal and in vitro experiments, described in BioMed Central's open access journal Arthritis Research and Therapy, have shown that mesenchymal stem cells (MSCs) taken from umbilical cord blood can suppress inflammation and attenuate collagen-induced arthritis.



Professor Zhan-guo Li worked with a team of researchers, from Peking University People's Hospital, China, to carry out the study. He said, "Very little is known about umbilical cord MSCs, and there has been no previous report about their use in the treatment of RA. MSCs can exert profound immunosuppression, which encourages their use in the treatment of autoimmune diseases, such as RA. At present, the most common source of MSCs has been bone marrow. However, aspirating bone marrow is an invasive procedure and the number and the differentiating potential of bone marrow MSCs decrease with age. In contrast, the collection of umbilical cord MSCs does not require any invasive procedure".



The researchers took immune cells from RA patients and showed that the umbilical MSCs were able to suppress the cells' proliferation, invasive behavior and inflammatory responses. Systemic infusion of the umbilical MSCs into mice was shown to significantly reduce the severity of collagen-induced arthritis. Speaking about the results, Professor Li said, "RA imparts a massive burden on health services worldwide and none of the currently used agents reaches long term drug-free remission. Therefore, a new and more effective therapy for RA will be very welcome".



Notes:


Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis

Yanying Liu, Rong Mu, Shiyao Wang, Li Long, Xia Liu, Ru Li, Jian Sun, Jianping Guo, Xiaoping Zhang, Jing Guo, Ping Yu, Chunlei Li, Xiangyuan Liu, Zhenyu Huang, Dapeng Wang, Hu Li, Zhifeng Gu, Bing Liu and Zhanguo Li

Arthritis Research & Therapy (in press)



Source:

Graeme Baldwin


BioMed Central

Gender Differences In Experience Of Rheumatism

Rheumatoid arthritis is often a more painful experience for women than it is for men, even though the visible symptoms are the same. Scientists are now saying that doctors should take more account of these subjective differences when assessing the need for medication. This and other findings are being presented at a congress currently in progress on gender medicine arranged by Karolinska Institutet.



For reasons yet unknown, rheumatoid arthritis is roughly three times more common amongst women than men. Moreover, several studies also suggest that rheumatoid arthritis eventually impairs the life quality of female suffers more than it does that of male sufferers. Here, too, the underlying reasons are unclear, but scientists have speculated that the medicines used affect women and men differently.



Researchers at Karolinska Institutet are now to present a study that gives vital clues as to why the prognosis is gender-specific. They have shown that men who undergo standard therapy for rheumatism respond significantly better than women having the same treatment - both objectively, such as in the degree of swelling in the joints, and subjectively in terms of their own experience of the disease.



"Purely objectively, the drug had a somewhat better effect on the men than on the women," says associate professor Ronald van Vollenhoven, who led the study. "But the greatest difference was of a subjective nature. The women in the study felt sicker even when their joints showed the same improvements."



According to Dr van Vollenhoven, it is important to take into account subjective difference when judging the severity of the disease. If doctors only consider the physical symptoms, people with severe pain might be deprived of the most effective medicine, which, owing to high costs and the risk of side-effects, is only given to the worst sufferers.



In a follow-up analysis, scientists compared the degree of disease in men and women who had received 'biological' medicines, which are only given to people who are considered seriously ill. The results of their study showed that while women and men who had been put on a course of treatment were at the same level as regards the objective manifestations of the disease, women felt themselves to be sicker than the men.



"Women and men have been treated on equal terms from the perspective of the doctors, but it's possible that no one has been aware of the fact that the pain can be worse for women than for men," says Dr van Vollenhoven. "Since our objective is to reduce suffering, we should try to take more account of the subjective aspects of rheumatoid arthritis."



Karolinska Institutet is one of the leading medical universities in Europe. Through research, education and information, Karolinska Institutet contributes to improving human health. Each year, the Nobel Assembly at Karolinska Institutet awards the Nobel Prize in Physiology or Medicine.

Karolinska Institutet

New Book For Parents Of Children With Juvenile Arthritis

The Arthritis Foundation announces the publication of a new book for
parents of children with juvenile arthritis (JA). Released in conjunction with Juvenile Arthritis
Awareness Month in July, the all-new Raising a Child with Arthritis addresses many of the concerns
parents have about JA - from diagnosis and treatments to family and financial issues.


From the editors of the Arthritis Foundation's Kids Get Arthritis Too award-winning national
newsletter, the book is written in easy to understand terms and offers solutions for the challenges
parents face when their child has arthritis. Raising a Child with Arthritis provides facts about various
types of JA and information about new treatments such as biologic drugs, while also providing
practical information on giving shots, navigating the education system, coping with flares and
managing daily activities without pain. In addition, parents and young adults who grew up with the
disease share their experiences and tips for success throughout the book.


"It is important for all parents of children with arthritis to gain knowledge about the disease
so it doesn't overshadow their child's life," says Patience H. White, M.D., M.A., Arthritis
Foundation chief public health officer and a pediatric rheumatologist. "With one in 250 children
diagnosed with arthritis or related conditions, it is essential for parents to feel empowered to assist
their child. This book can help them understand more about their child's disease and treatment
options to improve the quality of life for their child and family."


With nearly 300,000 children and teenagers under the age of 18 affected by arthritis or other
rheumatologic conditions, JA is one of the most common childhood diseases in the U.S. A study
conducted by the Centers for Disease Control and Prevention (CDC) shows that children diagnosed
with JA and other rheumatologic conditions account for approximately 827,000 doctor visits each
year, including an average of 83,000 emergency department visits.


In an ongoing effort to help youth with JA and their families, the Arthritis Foundation
recognizes Juvenile Arthritis Awareness Month each July and works to promote programs and
projects that bring attention to this over-looked disease. In addition to the release of Raising a Child
with Arthritis, the following Arthritis Foundation activities will take place in July during Juvenile
Arthritis Awareness Month:


- National JA Conference - The Arthritis Foundation hosts the National JA
Conference each year to bring together children with arthritis and their families along
with health professionals who are knowledgeable about JA. The goal is to help
families understand their treatment options, better cope with JA and find strength
from others living with arthritis. This year's conference will be held in Costa Mesa,
Calif. from July 10-13.















- Juvenile Arthritis Alliance Web Site Launch - In effort to provide more clear and
concise information to families living with JA, the Arthritis Foundation introduced
the Juvenile Arthritis Alliance Web site this month. The new site offers content
aimed at the entire community of people interested and involved in the lives of those
who have JA including parents, young adults, caregivers, teachers, health care
providers, researchers and advocates.


Raising a Child with Arthritis will be released on July 18. The Arthritis Foundation thanks
Amgen and Wyeth for underwriting the development of this book. Pre-order sales will begin on July
10. To order a copy of Raising a Child with Arthritis or for more information about Juvenile Arthritis
Awareness Month activities, visit arthritis/ja-information.


About the Arthritis Foundation


The Arthritis Foundation is the leading health organization addressing the needs of some 46
million Americans living with arthritis, the nation's most common cause of disability. Founded in
1948, with headquarters in Atlanta, the Arthritis Foundation has multiple service points located
throughout the country.
The Arthritis Foundation is the largest private, not-for-profit contributor to arthritis research
in the world, funding more than $380 million in research grants since 1948. Celebrating its 60th
anniversary this year, the foundation helps individuals take control of arthritis by providing public
health education; pursuing public policy and legislation; and conducting evidence-based programs to
improve the quality of life for those living with arthritis. Information is available 24 hours a day,
seven days a week at 1-800-283-7800 or arthritis.

The Arthritis Foundation

Natural Compounds Block Autoimmune Response In Diabetes, Arthritis

Natural compounds derived from a sea anemone extract and a shrub plant have been found to block the autoimmune disease response in type-1 diabetes and rheumatoid arthritis, according to University of California, Irvine researchers.



The study shows both in human and animal tests how these compounds work to deter the effect of autoimmune T-cells, white blood cells that attack the body. The goal, according to UCI researchers, is to develop new treatments from these compounds that will target these destructive T-cells while allowing other white blood cells to fight disease and infection.



Study results appeared Nov. 6-10 in the Early Online Edition of the Proceedings of the National Academy of Sciences.



The study, led by UC Irvine School of Medicine researchers George Chandy and Christine Beeton, identifies how these compounds work against a type of white blood cells called effector memory T lymphocytes, which play a major role in autoimmunity. Both compounds block an ion channel in these cells that prevents the cells from proliferating and producing chemicals called cytokines that attack the body during autoimmune disease states.



"Autoimmune diseases affect millions of Americans, and any new therapies that can aid them will have great significance," Chandy said. "What's promising about this study is that we identified a protein target on the T-cells that promote autoimmune activity and the compounds that can selectively block the target and shut down the destructive cells."



White blood cells patrol the body to fight against cancer and infections, but if some of these cells turn against the body they are meant to protect, they cause autoimmune diseases. Millions of people worldwide are afflicted with disabling autoimmune disorders. Two examples of this large class of diseases are type-1 diabetes, in which white blood cells attack the pancreas, and rheumatoid arthritis, in which the joints are attacked.



In their study, the UCI researchers used modified compounds derived from the rue plant (PAP-1) and a Cuban sea anemone extract (SL5), both of which block the ion channel in the destructive T-cells.



In one set of tests using blood samples from type-1 diabetes patients and joint fluid from people with rheumatoid arthritis, the researchers found that both compounds suppressed the function of the autoimmune T-cells without affecting other T-cells that fight infections.



In another set of tests using rats, the compound from the rue shrub plant delayed the onset and reduced the incidence of disease in diabetic rats, while the venom compound stopped the progression of the disease and improved the joint function of rats with experimental autoimmune arthritis. In these rat tests, the compounds were nontoxic.
















The Chandy laboratory previously discovered that SL5 compound was effective in treating rats with an experimental model of multiple sclerosis, another devastating autoimmune disease. Preclinical safety studies on PAP-1 and SL5 are under way in collaboration with AIRMID, a biotech company in the San Francisco Bay Area.



"We began our work on these natural products many years ago when we came across a report that described the beneficial effect of a scorpion sting on a patient with multiple sclerosis," Beeton said. "This work also speaks to the importance of protecting our plant and animal biodiversity -- you never know where a new medicine will come from."



Heike Wulff from University of California, Davis is a co-lead author, and other authors from UCI, UC Davis, Johns Hopkins University, Bachem Biosciences and the Benaroya Research Institute in Seattle are noted in the study text. The National Institutes of Health, American Diabetes Association, Juvenile Diabetes Research Foundation, National Multiple Sclerosis Society, Arthritis National Research Foundation and David Israelsky provided support for this study.



About type-1 diabetes and rheumatoid arthritis: The American Diabetes Association estimates that type-1 diabetes mellitus, also known as juvenile diabetes, affects one in every 400 or 600 children and adolescents in the U.S. It is characterized by a destruction of the cells that produce insulin in the pancreas. Without enough insulin, the body cannot correctly regulate levels of blood glucose, a major source of energy for the body. Type-1 diabetes can lead to serious complications such as heart disease, blindness, and nerve or kidney damage.



In rheumatoid arthritis, white blood cells induce inflammation in the joints, leading to muscle and joint aches, stiffness, and fatigue. According to the Arthritis Foundation, rheumatoid arthritis is one of the most serious and disabling types, affecting mostly women. An estimated 2.1 million people in the U.S. have rheumatoid arthritis. Some recent studies have suggested that the overall number of new cases of rheumatoid arthritis actually may be going down.






today.uci/news/release_detail.asp?key=1540



About the University of California, Irvine: The University of California, Irvine is a top-ranked university dedicated to research, scholarship and community service. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 24,000 undergraduate and graduate students and about 1,400 faculty members. The second-largest employer in dynamic Orange County, UCI contributes an annual economic impact of $3.3 billion. For more UCI news, visit today.uci/.



Contact: Tom Vasich


University of California - Irvine

Act On Official Audit, Arthritis Care Challenges 'Half-Hearted' Health Services, UK

Arthritis Care, the UK's largest support charity for people with arthritis, welcomes the National Audit Office report into rheumatoid arthritis services and urges health chiefs to implement its recommendations as swiftly as possible.



The audit highlights 'minimal' GP training in rheumatoid arthritis (RA) and poorly co-ordinated services, which the charity says means thousands of people with this devastating disease are failed by the system.



'The NAO report echoes what people with RA have been telling Arthritis Care for years - that it takes too long to get diagnosed. Early diagnosis and referral for suitable treatment is crucial as it can literally stop this debilitating condition in its tracks. We applaud the audit's recommendations that the Department of Health and Primary Care Trusts (PCTs) replace their often scattergun delivery with joined-up services. If actioned, the recommendations in this report should dramatically improve life for people with RA as well as save the country millions of pounds', said Neil Betteridge, Arthritis Care's chief executive.



44 year-old Elizabeth Ogg from West Sussex developed rheumatoid arthritis 6 years ago after the birth of her son. Elizabeth, who used to work as a management consultant, said: "It was terrifying when I started getting unbearable pains in my arms and legs. My mother urged me to see my doctor straight away - my father had RA and she recognised the potential symptoms immediately. Even with the private health care I had through my job, it still took over 6 months to get the correct diagnosis and start treatment.'



'After I was diagnosed, it became very clear that my GP at the time had very little understanding of RA, how severe it was or the medication that I would need to use. I didn't have any guidance or support and I was never referred to any specialist services, not even a physiotherapist - it was a disaster. Thankfully, I recently moved to West Sussex and since then I cannot praise the support I've had enough. My GP is wonderful - she has a special interest in rheumatology and I see a specialist nurse regularly as well as a physiotherapist and podiatrist. I'm finally getting the support I need to live with my condition. I can't believe the difference in service I've experienced - it just shouldn't be this way."



Arthritis Care believes that the key to addressing the majority of the problems identified by the NAO lies in the proper implementation of the Department of Health's Musculoskeletal Services Framework. The framework, launched in 2006 is a strategy for the delivery of integrated musculoskeletal services for England.



'The Musculoskeletal Services Framework was devised to improve services but any implementation has been intermittent and half-hearted. As the audit says, 73% of PCTs have not even undertaken any assessment to establish the number of people with RA in their areas. Arthritis Care is calling on the government and Strategic Health Authorities, plus every PCT, to respond to the audit by prioritising proper implementation of the framework. We also want to see a National Clinical Director for musculoskeletal services appointed to drive through improvements in services, just in the same way as one exists in the areas of mental health, diabetes and heart disease', says Betteridge.



Source
Arthritis Care

European Medicines Agency concludes action on COX-2 inhibitors

Concluding its review of the class of COX-2 inhibitors, the European Medicines Agency (EMEA) has recommended the
suspension of the marketing authorisation for Bextra (valdecoxib) and recommended new contraindications and warnings for
other COX-2 inhibitors that continue to be available in the European Union (EU). This builds on earlier regulatory actions
taken in February 2005.


COX-2 inhibitors are part of a broader class of medicines called non-steroidal anti-inflammatory drugs (NSAIDs), whose safety
profile will now also be examined.


At its 20-23 June 2005 meeting the Agency's Committee for Medicinal Products for Human Use (CHMP) said that additional
warnings and contraindications are necessary for all COX-2 inhibitors due to the cardiovascular risks, but concluded that the
additional risks of serious and potentially fatal skin reactions associated with the use of Bextra outweigh its benefits. The
suspension of Bextra will be reviewed within one year, during which time Pfizer has the opportunity to provide further safety
and other relevant data before the Committee can consider the re-introduction of the product in the EU. At the request of the
EMEA, Pfizer voluntarily agreed in April 2005 to withdraw the product from the market in the EU.


For the other COX-2 inhibitors (celecoxib, etoricoxib, lumiracoxib and parecoxib), the Committee agreed that the available
data show an increased risk of thrombotic adverse cardiovascular reactions, such as heart attacks and strokes. The CHMP
confirmed its February 2005 finding of an association between duration and dose of intake and the probability of suffering
such cardiovascular reactions. The Committee also confirmed that serious skin reactions occur with other COX-2 inhibitors,
but have been reported at lower rates than with Bextra. In concluding its review, the CHMP recommended the following
contraindications and precautions for these products:


-- Contraindications stating that COX-2 inhibitors must not be used in patients with established ischaemic heart disease
and/or cerebrovascular disease (stroke), and also in patients with peripheral arterial disease


-- Reinforced warnings to healthcare professionals to exercise caution when prescribing COX-2 inhibitors to patients with
risk factors for heart disease, such as hypertension, hyperlipidaemia (high cholesterol levels), diabetes and smoking















-- Given the association between cardiovascular risk and exposure to COX-2 inhibitors, doctors are advised to use the lowest
effective dose for the shortest possible duration of treatment


-- Additional or strengthened warnings to healthcare professionals and patients that hypersensitivity reactions and rare, but
serious and sometimes fatal, skin reactions can occur with all COX-2 inhibitors. In the majority of cases these occur in the
first month of use, and prescribers are warned that patients with a history of drug allergies may be at greater risk.
When prescribed in accordance with these additional contraindications and precautions, the Committee concluded that the
balance of benefits and risks remains positive for these COX-2 inhibitors used in their target patient populations. In
addition to any ongoing studies, the CHMP emphasised the importance for the authorisation holders for COX-2 inhibitors in the
EU (Merck Sharp & Dohme, Novartis and Pfizer) to continuously and carefully monitor and assess cardiovascular safety and
serious skin reactions.


The Committee assessed safety data for COX-2 inhibitors versus some conventional NSAIDs during the course of the review
procedure for the COX-2 inhibitors. On the basis of these data and following a request from the European Commission, the
Committee has now decided to look at the safety profile of NSAIDs to determine the need for further steps. This will build on
a review already started by the Committee's Pharmacovigilance Working Party on the safety of the most commonly used NSAIDs.



It is unclear if the findings for COX-2 inhibitors are also relevant for conventional NSAIDs. Pending any future
recommendations, healthcare professionals and patients should closely follow the product information for conventional NSAIDs
(whether prescription or non-prescription products) and COX-2 inhibitors. Patients who have concerns or questions should talk
to their doctor or pharmacist.


emea.eu.int


View drug information on Bextra.

Important Control Mechanism Behind Autoimmune Diseases Discovered

Researchers at the Swedish medical university Karolinska Institutet have discovered a new control mechanism in our immune system. The discovery is of potential significance to the treatment of serious diseases such as MS (multiple sclerosis), rheumatoid arthritis, and SLE (Systemic lupus erythematosus).


"Now that we've started to understand the regulatory mechanisms involved in these autoimmune diseases, we are hopeful that new treatments can be found," says Mikael Karlsson, associate professor at the Department of Medicine at Karolinska Institutet in Solna, and one of the team behind the study now published in the highly reputed periodical, The Journal of Experimental Medicine.


An important component of our immune defence is a type of cell called a B cell. Normally, the job of these cells is to produce antibodies, which in turn bind to and neutralise invasive microorganisms, such as bacteria and viruses. In people with an autoimmune disease, explains Dr Karlsson, these B cells actually have an injurious effect and instead of serving the body, are activated against its own tissues, which they start to break down.


Patients with SLE and other autoimmune diseases have lower levels of so-called NKT cells. Previously, it was not known what part these cells play in the origin and development of the disease; now, however, the research group at KI has shown that this deficiency is a contributory pathogenic factor.


"We've demonstrated that NKT cells can regulate how B cells become activated against healthy tissue, and that a lack of NKT cells results in greater misguided B cell activation," says Dr Karlsson. "So now we can mechanically link the NKT cell defect in patients to the disease."


The study also shows that the NKT cells directly impede faulty B cell activation, and that they do so early in the misdirected process. The team managed to inhibit the activity of pathogenic B cells by adding NKT cells - a result that may one day lead to new types of treatment.


"This means that new treatments specifically targeting the protective NKT cells can help this patient group," concludes Dr Karlsson.


Source: Karolinska Institutet

Obesity In Early Adulthood Associated With Increased Risk Of Psoriatic Arthritis

Among persons with psoriasis, those who reported being obese at age 18 had an increased risk of developing psoriatic arthritis, according to a report in the July 19 issue of Archives of Dermatology, one of the JAMA/Archives journals.



Psoriatic arthritis is a specific type of arthritis that develops in the joints of some patients who have psoriasis. According to background information in the article, "obesity has emerged as a significant risk factor for psoriasis," and "psoriatic arthritis affects 6 percent to 42 percent of people with psoriasis." Additionally, "psoriatic arthritis shares some clinical features with rheumatoid arthritis, both leading to joint destruction and significant morbidity."



Razieh Soltani-Arabshahi, M.D., of the University of Utah School of Medicine, Salt Lake City, and colleagues studied a volunteer sample of patients with dermatologist-diagnosed psoriasis enrolled in the Utah Psoriasis Initiative from November 2002 to October 2008. Of the 943 participants, 50.2 percent were women and psoriatic arthritis was present in 26.5 percent of participants with psoriasis (250 persons).



The study found that body mass index (BMI) at age 18 was predictive of psoriatic arthritis. Other predictors included younger age at psoriasis onset, being female and having larger body surface areas affected with psoriasis. Additionally, the findings show "the obese group having an earlier onset of psoriatic arthritis, followed by the overweight group and finally the normal BMI group." Twenty percent of the overweight or obese group developed psoriatic arthritis by age 35 years while 20 percent of those individuals in the normal BMI group developed psoriatic arthritis by age 48.



The authors conclude that their findings, "support a growing concept that patients more prone to psoriatic arthritis might benefit from more frequent and meticulous screening measures for early detection and treatment of psoriatic arthritis, i.e., before the development of irreversible joint destruction."
Arch Dermatol 2010;146[7]:721-726.


Source
Archives of Dermatology

Clinical Practitioners Not Adhering To Evidence-based Guidelines For Osteoarthritis

New research found clinicians who care for patients with osteoarthritis (OA) are likely not following standard care guidelines that are based on current medical evidence. Researchers noted physicians were prescribing medications for pain and inflammation, or opting for surgical interventions rather than recommending weight loss plans or exercise programs to OA patients. Details of the this study are available in the January 2011 issue of Arthritis Care & Research, a journal published by Wiley-Blackwell on behalf of the American College of Rheumatology.


A 2002 report by the World Health Organization (WHO) estimated OA to be the fourth leading cause of years lost due to disease (YLD) worldwide. OA disability is quickly becoming a major public health concern with experts suggesting that by 2020 the number of people with OA will have doubled due to growing obesity prevalence and the aging of the "baby boomer" generation. According to the Centers for Disease Control and Prevention (CDC), arthritis and other rheumatic conditions cost the U.S. $128 billion in 2003 a 24% increase since 1997. Much of the cost burden in arthritis care can be attributed to OA which accounts for a large volume of surgical procedures including total joint replacements.


Dr. David Hunter from the University of Sydney in Australia and New England Baptist Hospital in Boston, Massachusetts and colleagues reviewed how standard clinical practice diverges from evidence-based recommendations in the management of OA. "We present a potential roadmap for optimizing the quality of OA healthcare for those developing and enforcing policy decisions, and for clinicians on the frontlines of OA management to enact practice change," commented Dr. Hunter.


Current clinical practice does not reflect recommendations based upon medical evidence. The authors report that therapeutic interventions are primarily aimed at reducing pain and improving joint function by using therapies that target symptoms, but do not facilitate improvement in joint structure or long-term betterment of the disease. Frequently, physicians do not recommend conservative non-pharmacologic management therapies which leads to unnecessary diagnostic imaging and inappropriate referrals to orthopedic surgeons.


Many individuals with OA are overweight or obese. The authors support medical evidence which recommend a conservative non-pharmacologic management for OA patients. "Weight management and exercise programs tend to be overlooked by clinicians," said Dr. Hunter. "These conservative approaches are beneficial to patients who adhere to weight-loss and exercise programs."


Researchers further suggest that surgery be resisted when symptoms can be well managed by other treatment methods. The typical indications for a surgical approach in treating OA are debilitating pain and major limitation of functions such as walking, working, or sleeping. However, prior studies have shown that up to 30% of some surgical procedures are inappropriate and recent recommendations suggest routine arthroscopy for knee OA management should be avoided something not reflected in clinical practice.


The study team also noted an overuse of inappropriate diagnostic imaging instead of clinical diagnosis based on history and physical examination. Based on current guidelines imaging should be reserved for instances where a diagnosis is unclear and radiography could rule out other diseases that may produce similar symptoms. Research studies estimate there are 95 million high-tech scans (CT, MRI, PET) done annually in the U.S representing a $100 billion industry, of which $14 billion has been shouldered by Medicare and 20% to 50% of these scans were unnecessary as the results failed to help treat or diagnose the patient's symptoms.


"Eliminating unproven procedures and reducing needless costs is necessary to improve the quality and lower the cost of healthcare in the U.S.," concluded Dr. Hunter. "The management of OA should focus on a patient-centered and provider integrated approach that improves quality and reduces cost by following evidence-based recommendations."


Sources: Wiley - Blackwell, AlphaGalileo Foundation.

Increase Of Hip And Knee Replacements In The U.S.

With the graying of America's Baby Boomer generation, arthritis is a growing health concern. Traditionally associated with the elderly, this common joint disease currently afflicts over 20 million men and women in the United States. To aggravate matters, arthritis is also prevalent among the overweight - which describes nearly 65 percent of our nation's adult population. Fortunately, treating the pain and disability of arthritis has been revolutionized by surgical joint replacements of the hips and knees. Unfortunately, as hip and knee replacements have become a more popular option, the toll on Medicare, private insurers and hospitals has escalated. Despite its huge implications for the healthcare system, the projected impact of joint replacements has attracted scant study.



To assess and address this issue, Sunny Kim, PhD, a researcher with the Robert Stempel School of Public Health at Florida International University, started with one of the largest databases of hospital procedures available: the Nationwide Inpatient Sample (NIS). Using the latest revision of international procedure coding, Dr. Kim identified joint replacement cases throughout the US and analyzed increases in surgeries and costs between 1997 and 2004. The April 2008 issue of Arthritis Care & Research (interscience.wiley/journal/arthritis) presents hard-hitting numbers to back her conclusion: "the burden resulting from hip/knee joint replacement is not only substantial but also increasing at a steep rate."



Among Dr. Kim's significant, distressing findings:

In 2004, approximately 431,485 primary knee replacements were performed - a 53 percent increase from the year 2000. 225,900 primary hip replacements were performed in the US - marking a 37 percent increase for the same period.



In 1997, about 60 of primary hip replacements and 69 percent of primary knee replacements were performed on individuals between the ages of 65 and 84 years. Although elderly patients remained the main recipients, the number of joint replacement surgeries among the middle-aged, patients between 45 and 64 years, increased excessively - 71 percent for hip replacements and 83 percent for knee replacements - in 2004.



Between 1997 and 2004, the hospital charges for joint replacements, both primary and revision surgeries, increased faster than the rate of inflation. While Medicare continued to provide the principal source of payment, compared with other sources of payment, the relative burden decreased. The burden on private insurance more than tripled in that 7-year span - from $1.1 billion to $3 billion for hip replacements and from $1.46 billion to $4.64 billion for knee replacements.



If current trends persist, nearly 600,000 hip replacements and 1.4 million knee replacements will be performed in the year 2015.

Reflecting on the rise in the numbers of joint replacements and in surgeries among younger patients, Dr. Kim raises decreased lack of tolerance for pain and increased acceptance of surgical safety, as well as the impact of obesity, as possible explanations. She also acknowledges the study's inability to track the rates and costs of a less-invasive surgery for hip and knee replacements, performed on an outpatient basis for selected patients.



Calling for the creation of a national joint replacement registry as one key step, Dr. Kim stresses the need for urgent attention to the problems that come with the territory of this popular, radical arthritis treatment. "Public health education is critically important to reduce the proportion of people who are overweight as well as to manage arthritis at earlier stages," she notes. "At the same time, given the steeply increasing trends of joint replacements and the expected number of joint revisions needed, the health care community should be prepared for this upcoming demand of surgical loads and its economic burden on government and private insurance systems."



Article: "Changes in Surgical Loads and Economic Burden of Hip and Knee Replacements in the US: 1997-2004," Sunny Kim, Arthritis & Rheumatism (Arthritis Care & Research), April 15, 2008; 59:4, pp. 481-488.







Source: Sean Wagner


Wiley-Blackwell