Animal Model Of Rheumatoid Arthritis (KRN-CTM) Deepens Understanding Of The Disease

Current research provides a novel model for rheumatoid arthritis research. The related report by LaBranche et al, "Characterization of the KRN cell transfer model of rheumatoid arthritis (KRN-CTM), a chronic yet synchronized version of the K/BxN mouse," appears in the September 2010 issue of The American Journal of Pathology.



Nearly 1% of the population is affected by rheumatoid arthritis, and women are affected three to five times more often then men. Although the course of disease varies greatly, daily living activities are impaired in most affected individuals and after 5 years approximately 33% of sufferers are no longer able to work.



Rheumatoid arthritis is characterized by chronic inflammation of the distal joints and is mediated in part by emigration and activation of immune cells. The restrictions of present animal models, which either mimic chronic disease or a synchronized version of early disease (but not both), have hampered scientific understanding of the specific roles immune cells and their mediators play in disease initiation and maintenance. In this regard, Dr. Paul Allen and colleagues at the Washington University in St. Louis School of Medicine, in collaboration with Dr. Timothy LaBranche and colleagues at Pfizer Global Research & Development developed and characterized a chronic yet synchronized animal model of rheumatoid arthritis (KRN-CTM). Disease in these animals developed with a uniform onset of 7 days post-initiation and was maintained chronically (through Day 42). These mice revealed a time course of rheumatoid arthritis characteristics including edema, immune cell infiltration, cartilage damage and osteoclast-mediated bone resorption.



According to Dr. LaBranche, "the main benefit of the KRN-CTM is its utility, which adds significant logistical and platform advantages to study T cell targets since the model is T cell-dependent and engages both early and late stages of innate and adaptive immune responses (a drawback of the antibody-dependent K/BxN serum transfer model). In addition, by polarizing T helper (Th) cells and/or knocking down genes prior to transfer, the KRN-CTM may enable investigators to ask how specific Th subsets and/or specific T cell genes contribute to disease. Lastly, incidence, onset, and severity of disease are highly synchronized without requiring adjuvant. The KRN-CTM presents a novel opportunity for investigators to study specific pathways and mechanisms involved in both the early and chronic phases of disease, thereby enabling the validation of targets and biopharmaceuticals for rheumatoid arthritis patients."



In future studies Dr.'s Allen and LaBranche aim to demonstrate the utility of the KRN-CTM, illustrating the roles Th subsets and particular genes have in both the model and people.

Level Of Osteoarthritis Pain May Determine Efficacy Of Glucosamine, Chondroitin Sulfate

The popular dietary supplements glucosamine and chondroitin sulfate proved no better than a placebo in relieving osteoarthritis knee pain in most participants of a major national trial. But the study, published in the Feb. 23 issue of the New England Journal of Medicine, also showed a smaller subgroup of trial patients with moderate to severe osteoarthritis knee pain taking the combination of the two supplements experienced significant pain relief.



"For the study population as a whole, supplements were found to be ineffective," said rheumatologist Daniel O. Clegg, M.D., professor of medicine at the University of Utah School of Medicine, chief of rheumatology at the George E. Wahlen Veterans Affairs Medical Center in Salt Lake City, and principal investigator for the national trial. "An exploratory analysis suggested, however, that the combination of glucosamine and chondroitin sulfate might be effective in patients who suffer from moderate to severe osteoarthritis knee pain."



Glucosamine, an amino sugar the body produces and distributes in cartilage and other connective tissue, and chondroitin sulfate, a complex carbohydrate that helps cartilage retain water, have become popular remedies among osteoarthritis sufferers in recent decades. But evidence of the supplements' ability to control pain had been anecdotal.



The five-year, $12.5 million Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) was designed to rigorously assess the efficacy and safety of glucosamine and chondroitin sulfate, taken either separately or in combination. Nearly 1,600 patients with painful knee osteoarthritis were enrolled in the trial and randomly assigned to take placebo, celecoxib (a widely prescribed arthritis pain drug), glucosamine, chondroitin sulfate, or a combination of the two supplements for 24 weeks. Of the 1,583 study patients, 78 percent were in the mild knee pain subgroup and the remaining 22 percent were in the moderate to severe subgroup.



Celecoxib served as the study's positive control because it is an approved osteoarthritis pain drug and participants would be expected to respond in a predictable way.



For all trial patients, celecoxib proved most effective in providing significant pain relief, with a 70 percent response rate, compared to 64 percent for glucosamine and 65 percent for chondroitin sulfate. Taken in combination, the supplements provided significant relief for 66 percent of patients who receive them. The response rate in those who took placebo was 60 percent.



In participants in the mild knee pain subgroup, celecoxib proved the most effective, significantly improving pain relief for 70 percent of those who took it, compared to nearly 64 percent for glucosamine, 67 percent for chondroitin sulfate, and 63 percent for the combination of the two. Placebo produced a 62 percent response rate for people with mild pain.
















"As we expected, patients who took celecoxib showed significant improvement in pain relief," Clegg said.



In patients in the moderate-to-severe knee pain subgroup, however, the combination of the two supplements appeared to be more effective than placebo, significantly reducing pain in 79 percent of those who received it. This is compared with 69 percent who took celecoxib and 54 percent who took placebo. Because only 22 percent of the trial participants were in the moderate-to-severe subgroup, this result should be considered preliminary and further study will be required to confirm these results, according to Clegg.



Conducted at 16 U.S. academic rheumatology centers, the study was funded by the National Center for Complementary and Alternative Medicine (NCCAM) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), components of the National Institutes of Health.



Study participants were required to have both pain and X-ray evidence of osteoarthritis in their knees. They were evaluated at the beginning of the trial and at weeks four, eight, 16, and 24, with a positive treatment response defined as a 20 percent or greater decrease in knee pain compared to the start of the study.



More than 20 million Americans have osteoarthritis. Oral doses of glucosamine and chondroitin sulfate, derived from animal products, have become popular with arthritis sufferers in the past 20 or so years.



"I urge people with osteoarthritis to follow a comprehensive plan for managing their arthritis pain. Developing and maintaining a healthy lifestyle is key to the successful management of osteoarthritis--eat right, exercise regularly, lose excess weight, and consider the use of medications based on your degree of pain," Clegg said.



In a second part of the study, Clegg and other researchers will track whether taking glucosamine and chondroitin sulfate alone and in combination affects progression of knee osteoarthritis. All participants in the second part of the study had a knee X-ray at the beginning of the trial and will be imaged again at years one and two. X-rays will be compared and evaluated to assess whether these supplements affect progression of osteoarthritis. Results of the second part of the study are expected in about a year.







Contact: Phil Sahm

Phil.Sahmhsc.utah

University of Utah Health Sciences Center

Zimmer Holdings And ISTO Technologies Announce Start Of Neocartilage Clinical Trial

Zimmer
Holdings, Inc. (NYSE: ZMH; SWX: ZMH), a leader in the orthopaedics
industry, and ISTO Technologies, Inc., an innovative orthobiologic company,
today announced that the clinical trial is now underway for Neocartilage, a
living tissue-engineered graft under investigation for the restoration of
cartilage defects, reestablishment of joint function and relief of pain in
the knee. Zimmer plans to market the product as DeNovo(R) ET Engineered
Tissue Graft.


In June 2006, the U.S. Food and Drug Administration (FDA) approved
ISTO's Investigational New Drug (IND) application, allowing the companies
to move forward with human clinical trials of the novel cartilage
regeneration treatment.



Jack Farr II, M.D., an orthopaedic surgeon with OrthoIndy,
Indianapolis, performed the surgery on the first patient in November 2006.
"I have participated in a variety of projects involving cartilage repair
and regeneration, and I find the science behind DeNovo ET very compelling,"
said Dr. Farr. "The initial surgery went as we had hoped, and we look
forward to enrolling more patients into the study and serially assessing
their progress with the implant."



Kevin F. Bonner, M.D., an orthopaedic surgeon with Jordan-Young
Institute in Virginia Beach, Virginia, has also enrolled patients into the
study. "In pre-clinical studies, DeNovo ET has demonstrated the ability to
resurface cartilage defects," said Dr. Bonner. "The procedure is
straightforward and builds on earlier cartilage repair techniques."



Additional study sites for the clinical trial are being added.
Recently, Rush University Medical Center in Chicago was added; Dr. Brian
Cole, the head of Rush's Cartilage Restoration Center, will serve as the
principal investigator for the Rush location.



Zimmer and ISTO entered into a co-development agreement in 2002
granting Zimmer exclusive worldwide commercial distribution rights to the
Neocartilage technology. The two companies have since collaborated on
further development and pre-clinical testing. The potential market for
DeNovo ET is large, as each year in the United States alone approximately
500,000 cartilage lesions are treated in knee joints.



"We are delighted both to advance the Neocartilage technology into
human clinical trials, and to be collaborating with the world's leading
orthopaedic company to achieve this significant milestone," said Mitchell
Seyedin Ph.D., President and Chief Executive Officer of ISTO.



"Zimmer has made biologics the centerpiece of our innovative investment
strategy and we are pleased to have reached this very concrete milestone in
the development of our plans," said Ray Elliott, Chairman, President and
Chief Executive Officer of Zimmer Holdings. "With our investments in other
biologic repair and regeneration technologies, we intend to play a
leadership role in the next generation of treatments to address the needs
of patients with arthritis and other orthopaedic issues."
















DeNovo ET is a living tissue graft grown from juvenile chondrocytes
(cartilage cells) using ISTO's proprietary cell-based platform technology.
Studies have demonstrated that juvenile chondrocytes produce cartilage
significantly better than their adult counterparts. Cartilage works as a
low friction articulating surface to protect joints from wear and tear
experienced during motion. Articular cartilage can be damaged as a result
of injury, or can simply deteriorate over time leading to osteoarthritis.
Cartilage is known to have limited capacity to heal on its own. Most joint
replacements are performed as a result of the effects of osteoarthritis.



Zimmer is also developing another cartilage repair product in
conjunction with ISTO. The DeNovo NT Natural Tissue Graft also consists of
juvenile chondrocytes in the form of minced cartilage tissue. This living
tissue graft is also intended to support the surgical repair of damaged
articular cartilage.



About Zimmer



Founded in 1927 and headquartered in Warsaw, Indiana, Zimmer is the
worldwide #1 pure-play orthopaedic leader in designing, developing,
manufacturing and marketing reconstructive and spinal implants, trauma and
related orthopaedic surgical products. Zimmer has operations in more than
24 countries around the world and sells products in more than 100
countries. Zimmer's 2006 sales were approximately $3.5 billion. The Company
is supported by the efforts of nearly 7,000 employees worldwide.



About ISTO Technologies, Inc.



ISTO Technologies, Inc. is an orthobiologic company focused on
developing differentiated products for sports medicine and spinal therapy.
ISTO's products are intended for repair and regeneration of damaged
cartilage in joints and spinal discs.



Visit Zimmer on the worldwide web at zimmer



Zimmer Safe Harbor Statement



This press release contains forward-looking statements within the safe
harbor provisions of the Private Securities Litigation Reform Act of 1995
based on current expectations, estimates, forecasts and projections about
the orthopaedics industry, management's beliefs and assumptions made by
management. Forward-looking statements may be identified by the use of
forward-looking terms such as "may," "will," "expects," "believes,"
"anticipates," "plans," "estimates," "projects," "assumes," "guides,"
"targets," "forecasts," and "seeks" or the negative of such terms or other
variations on such terms or comparable terminology. These statements are
not guarantees of future performance and involve risks, uncertainties and
assumptions that could cause actual outcomes and results to differ
materially. These risks and uncertainties include, but are not limited to,
our ability to successfully integrate acquired businesses, the outcome of
the Department of Justice investigations announced in March 2005 and June
2006, price and product competition, rapid technological development,
demographic changes, dependence on new product development, the mix of our
products and services, supply and prices of raw materials and products,
customer demand for our products and services, control of costs and
expenses, our ability to conduct a successful search for a new chief
executive officer and the ability of the new chief executive officer to
gain proficiency in leading our company, our ability to form and implement
alliances, international growth, governmental laws and regulations
affecting our U.S. and international businesses, including tax obligations
and risks, product liability and intellectual property litigation losses,
reimbursement levels from third-party payors, general industry and market
conditions and growth rates and general domestic and international economic
conditions including interest rate and currency exchange rate fluctuations.
For a further list and description of such risks and uncertainties, see our
periodic reports filed with the U.S. Securities and Exchange Commission. We
disclaim any intention or obligation to update or revise any
forward-looking statements, whether as a result of new information, future
events or otherwise, except as may be set forth in our periodic reports.
Readers of this document are cautioned not to place undue reliance on these
forward-looking statements, since, while we believe the assumptions on
which the forward-looking statements are based are reasonable, there can be
no assurance that these forward-looking statements will prove to be
accurate. This cautionary statement is applicable to all forward-looking
statements contained in this document.


Zimmer Holdings, Inc.

zimmer

Actemra Approved In Japan To Treat Patients With Rheumatoid Arthritis

Roche announced that their alliance partner company Chugai has received approval in Japan for the use of its innovative treatment, Actemra (tocilizumab), in patients suffering from rheumatoid arthritis (RA).


Actemra was approved by the Japanese authorities for the indication of rheumatoid arthritis (including prevention of structural damage of joints) and two forms of the disease that affect children, know as juvenile idiopathic arthritis and systemic-onset juvenile idiopathic arthritis.


Japan is the first market worldwide to get access to Actemra for the treatment of RA. The approval is based on compelling data from clinical trials conducted in Japan that showed Actemra was highly effective in controlling the symptoms and progression of this serious disease.


"Today's approval represents a significant milestone for rheumatologists and patients in Japan. The Japanese authorities have recognized that Actemra is a breakthrough drug which addresses an unmet medical need for patients suffering from the debilitating effects of this disease" said William Burns, CEO Roche Pharmaceuticals Division.


Actemra is the first of a new class of drug with a novel mechanism of action that brings new hope to RA patients. It is a humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody, which works by suppressing the activity of IL-6, an important trigger of the inflammatory process. This novel mode of action reduces inflammation of the joints and relieves the systemic effects of RA.


Since 2005, Actemra has been marketed in Japan for the treatment of patients with a rare auto-immume condition known as Castleman's disease. Actemra licence applications have also been filed for treatment of RA in the Unites States and the European Union in 2007, and are currently under review.


Rheumatoid Arthritis - A High Unmet Medical Need


Rheumatoid arthritis is a progressive autoimmune disease characterized by inflammation of the membrane lining in the joints throughout the body. This inflammation causes distortion of the joint and impaired function accompanied by pain, stiffness and swelling and ultimately leading to irreversible joint destruction and disability. In addition, the systemic symptoms of RA include fatigue, anaemia, osteoporosis and may contribute to shortening life expectancy by affecting major organ systems. Sadly after 10 years, less than 50% of patients can continue to work or function normally on a daily basis.















Juvenile idiopathic arthritis is the collective term for diseases with unknown cause associated with symptoms in joints occurring in children aged below sixteen. While clinical findings of pJIA have many similarities to rheumatoid arthritis, sJIA is accompanied by systemic symptoms, mostly remittent fever, and is considered a very severe disease.


About Actemra


Actemra is the result of research collaboration by Chugai and is being co-developed globally with Chugai. Actemra is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody. An extensive clinical development program of five Phase III trials was designed to evaluate clinical findings of Actemra. Four studies are completed and have reported meeting their primary endpoints. A fifth trial, a two-year study called LITHE (TociLIzumab safety and THE prevention of structural joint damage), is currently underway and is expected to report preliminary first-year data in 2008. Actemra is awaiting approval in the United States and Europe. In Japan, Actemra was launched by Chugai in June 2005 as a therapy for Castleman's disease; in April 2008, additional indications for rheumatoid arthritis, juvenile idiopathic arthritis and systemic-onset juvenile idiopathic arthritis were also approved in Japan.


Actemra is generally well tolerated. The overall safety profile of Actemra is consistent across all global clinical studies. The most common, non-serious, adverse events reported are upper respiratory tract infection, nasopharyngitis, headache and hypertension. As with other biological disease modifying anti-rheumatic drugs (DMARDs), serious infections and hypersensitivity reactions including a few cases of anaphylaxis, have been reported in some patients treated with Actemra. Increases in liver transaminases (ALT and AST) were seen in some patients; these increases were generally mild and reversible, with no hepatic injuries or any observed impact on liver function.


About Roche in rheumatoid arthritis


One of the most important drivers for growth at Roche over the next few years is expected to be the company's emerging franchise in autoimmune diseases with rheumatoid arthritis as the first indication. Following the launch of MabThera (rituximab) there are a number of projects in development, potentially allowing Roche to build on further opportunities. MabThera is the first and only selective B-cell therapy for RA, providing a fundamentally different treatment approach by targeting B cells, one of the key players in the pathogenesis of RA. Actemra is Roche's second novel medicine and is a humanised monoclonal antibody to the interleukin-6 (IL-6) receptor, inhibiting the activity of IL-6 , a protein that plays a major role in the RA inflammation process. Additional projects creating a rich pipeline include compounds in Phase I, II and III clinical trials. Notably, ocrelizumab, a humanised anti-CD20 antibody, has entered phase III development for RA.


About Roche


Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world's biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, and is a market leader in virology. It is also active in other major therapeutic areas such as autoimmune diseases, inflammatory and metabolic disorders and diseases of the central nervous system. In 2007 sales by the Pharmaceuticals Division totalled 36.8 billion Swiss francs, and the Diagnostics Division posted sales of 9.3 billion francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invested over 8 billion Swiss francs in R&D in 2007. Worldwide, the Group employs about 79,000 people. Additional information is available on the Internet at roche.


All trademarks used or mentioned in this release are protected by law.


Further information


- Roche & Autoimmune diseases

- Chugai


roche


View drug information on Actemra.

NEXIUM(R) Shown To Reduce Gastric Ulcers In At-Risk Patients Using Long-Term NSAIDs

Results from two
clinical trials, to be published in the April 2006 edition of the American
Journal of Gastroenterology, indicate that NEXIUM(R) (esomeprazole magnesium)
can reduce the incidence of gastric (stomach) ulcers in patients at risk of
developing gastric ulcers and who regularly take either non-selective
nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2-selective NSAIDs.(1)
NSAIDs are a class of pain relief medications that include traditional,
non-selective drugs, such as ibuprofen, naproxen and aspirin, and newer COX-2-
selective agents. Non-selective NSAIDs are known for increasing the risk of
gastric ulcers, particularly among older patients who take them regularly or
who have a history of gastric ulcers.


Pooled data from the double-blind, randomized, six-month trials showed
that significantly fewer patients taking either NEXIUM 20 mg or NEXIUM 40 mg,
in addition to their regular non-selective NSAID/COX-2-selective therapy,
developed an ulcer at six months, compared to those taking a placebo (5.2
percent and 4.6 percent, respectively, vs. 17 percent, p







AstraZeneca R&D, Sweden, funded the study through a research grant.


About NSAID-ulcer Risk


Chronic NSAID use is a common cause of gastric ulcers and has been
associated with side effects ranging from indigestion to potentially life-
threatening stomach bleeding.(2) Of the more than 14 million Americans who
use NSAIDs regularly to treat chronic pain,(3) up to 25% may be affected by
NSAID-related ulcers.(4) Each year, there are an estimated 103,000
hospitalizations and 16,500 deaths in the United States attributed to
complications from NSAID-associated gastric ulcers.(5) Among the elderly,
NSAID use accounts for nearly one third of gastric-ulcer-related
hospitalizations,(6) with an associated four-fold increased risk of death.(7)


About NEXIUM(R) (esomeprazole magnesium) Delayed-release Capsules


NEXIUM is indicated for reducing the risk of gastric ulcers developing
among at-risk patients on continuous NSAID therapy. Patients are considered
to be at risk if they are age 60 plus or if they have a history of previous
gastric ulcer. NEXIUM also is approved for treating frequent, persistent
heartburn and other symptoms associated with acid reflux disease, as well as
for the healing and maintenance of erosive esophagitis, a condition in which
stomach acid begins to wear away the inner lining of the esophagus. Most
erosions heal in four to eight weeks. Individual results may vary, and only a
doctor can determine if erosions to the esophagus have occurred. Symptom
relief does not rule out the existence of other serious stomach conditions.
The most frequently reported adverse events with NEXIUM include headache,
diarrhea and abdominal pain. For full prescribing information for NEXIUM,
please visit nexium-us.


About AstraZeneca


AstraZeneca (NYSE: AZN) is a major international healthcare business
engaged in the research, development, manufacture, and marketing of
prescription pharmaceuticals and the supply of healthcare services. It is one
of the world's leading pharmaceutical companies with healthcare sales of
$23.95 billion and leading positions in sales of gastrointestinal,
cardiovascular, neuroscience, respiratory, oncology, and infection products.
In the United States, AstraZeneca is a $10.77 billion healthcare business with
more than 12,000 employees. AstraZeneca is listed in the Dow Jones
Sustainability Index (Global) as well as the FTSE4Good Index.
For more information about AstraZeneca, please visit:
astrazeneca-us.


This press release contains forward-looking statements with respect to
AstraZeneca's business. By their nature, forward-looking statements and
forecasts involve risks and uncertainties because they relate to events and
depend on circumstances that will occur in the future. There are a number of
factors that could cause actual results and developments to differ materially.
For a discussion of those risks and uncertainties, please see the company's
Annual Report/Form 20-F for 2005.


References


1 Scheiman JM, et al. (2006) Prevention of Ulcers by Esomeprazole in At-
Risk Patients Using Non-Selective NSAIDs and COX-2 Inhibitors. Am J
Gastroenterology 0 (0), -.doi: 10.1111/j.1572-0241.2006.00499.x.


2 Scheiman JM and Fendrick AM. Practical approaches to minimizing
gastrointestinal and cardiovascular safety concerns with COX-2 inhibitors
and NSAIDs. Arthritis Research & Therapy 2005, 7(Suppl 4):S23-S29.


3 The Dangers of Aspirin and NSAIDs. American College of
Gastroenterology. Available at:

acg.gi/patients/women/asprin.asp.


4 Blower AL. Scand J Rheumatol 1996;25(suppl 105):13-26.

Singh G. Am J Med 1998;105:31S-38S.


5 Wolfe M, Lichtenstein R, Singh G. Gastrointestinal toxicity of
nonsteroidal anti-inflammatory drugs. N Engl J Med 1999;340:1888-1899.


6 Griffin MR et al. Nonsteroidal anti-inflammatory drug use and
increased risk for peptic ulcer disease in elderly persons. Ann Intern
Med 1991;114:257-263.


Griffin MR et al. Nonsteroidal anti-inflammatory drug use and death
from peptic ulcer disease in elderly persons. Ann Intern Med
1988;109:359-363.


Laine L et al. Gastrointestinal health care resource utilization with
chronic use of COX-2-specific inhibitors versus traditional NSAIDs.
Gastroenterology 2003;125:389-395.


(All citations above from Abraham NS et al. National adherence to
evidence-based guidelines for the prescription of nonsteroidal anti-
inflammatory drugs. Gastroenterology 2005;129:1171-1178.)


7 Griffin MR et al. Nonsteroidal anti-inflammatory drug use and death
from peptic ulcer disease in elderly persons. Ann Intern Med
1988;109:359-363. From Abraham NS et al. National adherence to evidence-
based guidelines for the prescription of nonsteroidal anti-inflammatory
drugs. Gastroenterology 2005;129:1171-1178.


AstraZeneca

astrazeneca-us

nexium-us


View drug information on Nexium.

Improved Rheumatoid Arthritis Remission With Combined Therapy

For
patients with active, early stage, moderate-to-severe rheumatoid
arthritis, a combination treatment with methotrexate and etanercept can
improve remission and radiographic non-progression rates within one
year in comparison with just methotrexate. Additionally, more patients
are also able to remain employed. These conclusions are published in an
article released early Online on July 16, 2008 in The Lancet.




Rheumatoid
arthritis is an autoimmune disorder in which the immune system attacks
the joints, causing arthritic inflammation and damage. It can also
extend to other parts of the body. Early in therapy, successful
treatments induce remission, usually by reducing or eliminating
inflammation. If progression of the disease is caught at an early
stage, when it can be most destructive, serious joint damage could be
prevented.



To investigate potential treatment methods for
rheumatoid arthritis, Paul Emery, Professor of Rheumatology, University
of Leeds, UK and Leeds Teaching Hospitals Trust, UK, performed the
COMET study, a randomized trial comparing combination treatment with
individual treatment. A total 542 patients with early
moderate-to-severe RA for 3-24 months who had not been treated with
methotrexate were randomle assigned to one of the following groups:
only methotrexate (268 patients), or methotrexate and etanercept (274
patients). Methotrexate was administered with a starting dose of 7.5 mg
per week to a maximum 20 mg per week at the end of 8 weeks. The
entanercept was administered at 50 mg per week. A disease activity
score (DAS28) was evaluated with a radiographic non-progression measure
(Sharp score) after one year.



It was found that 50% of patients who were given the combined treatment
achieved remission, while 94% of this group had a good to moderate
response. In comparison, the methotrexate only group had a 28%
remission rate, making the combined group members almost twice as
likely to achieve remission. In a comparison of radiographic
non-progression, 80% of combined treatment patients achieved the mark,
while only 58% achieved this in the only methotrexate group. The
serious adverse events were similar in the two groups.



The authors summarize their findings while making a statement about the
increased functionality of patients who are able to bring rheumatoid
arthritis into remission early. "The COMET trial showed that patients
who received combination therapy have a nearly three-fold reduction in
work stoppage compared with those who took high- dose methotrexate
alone. The ability to remain a productive member of the workforce has
implications for patients, employers, and society as a whole. The
effect of RA is especially significant for women aged 55-64 years,
because they have a high incidence of stopping work early...nearly a
quarter of patients who were in employment at baseline in the COMET
trial had stopped working at least once by the end of 1 year compared
with about a tenth in the combination group."



According to the authors, this is data is evidence for the combined
treatment. "The results of the COMET trial suggest that remission is an
achievable goal in patients with early severe RA within the first year
of therapy with etanercept plus methotrexate....The positive clinical
outcomes in the combination treatment group also seem to determine the
ability of patients to remain in employment. Furthermore, these
outcomes appear to be achieved without exposing patients to significant
additional risk."



Dr Joel Kremer, Center for Rheumatology, Albany Medical College,
Albany, NY, USA, contributed an accompanying comment stating that there
must be a specific system for ensuring that this kind of therapy is
cost effective and efficiently implemented. "Experts in health
economics can apply rigorous formulae to quality of life and
disability, while factoring in cost of drugs and their toxic effects,
to establish whether the promising data in these investigations are
sustained, and whether the new biological agents are cost effective."
He says.



Comparison
of methotrexate monotherapy with a combination of methotrexate and
etanercept in active, early, moderate to severe rheumatoid arthritis
(COMET): a randomised, double-blind, parallel treatment trial

Paul
Emery, Ferdinand C Breedveld, Stephen Hall, Patrick Durez, David J
Chang, Deborah Robertson, Amitabh Singh, Ronald D Pedersen, Andrew S
Koenig, Bruce Freundlich

Published Online The Lancet July 16, 2008

DOI:10.1016/S0140- 6736(08)61000-4

Click Here For Journal



COMET's path, and the new biologicals in rheumatoid arthritis

Joel M Kremer

Published Online The Lancet July 16, 2008

DOI:10.1016/S0140- 6736(08)61001-6

Click Here For Journal



Written by Anna Sophia McKenney

Northwestern Memorial Study Tests Cancer Drug On Scleroderma Patients

Physicians at Northwestern
Memorial Hospital are studying the effects of an anti-cancer drug to treat
patients with scleroderma, a rare, incurable autoimmune rheumatic disease
that leads to hardening and tightening of the skin and connective tissues.
Scleroderma affects an estimated 300,000 people in the United States and
can often attack the lungs, heart, kidneys and intestinal tract, and
sometimes lead to death.


The study is the first of its kind to examine if Gleevec, a cancer drug
commonly used to treat leukemia, will treat the skin thickness in
scleroderma patients by blocking the pathway that causes fibrosis. Patients
enrolled in the clinical trial will receive daily oral doses of Gleevec for
six months and will be evaluated initially on a weekly basis at
Northwestern Memorial, one of only three centers nationwide participating
in the study. Others include Johns Hopkins and Boston University Medical
Center.



John Varga, MD, rheumatologist at Northwestern Memorial, John and Nancy
Hughes Distinguished Professor in Rheumatology at Northwestern University's
Feinberg School of Medicine and principal investigator of the study, said
this could be a big step forward for people diagnosed with scleroderma.
"Based on recent research performed by investigators at the Feinberg
School, Gleevec shows potential efficacy in reducing the abnormal skin
changes associated with scleroderma."



The exact cause of Scleroderma, a chronic disease most commonly found
in women between the ages of 30 and 40, remains unknown. Through continued
research, Northwestern Memorial physicians hope to identify treatments to
target the disease and improve the quality of life for patients living with
Scleroderma.



"We hope that the use of Gleevec for a sustained period of time will
decrease the symptoms of skin hardening, and potentially slow the
progression of this devastating disease," adds Dr. Varga.



About Northwestern Memorial Hospital



Northwestern Memorial Hospital is one of the country's premier academic
medical centers and is the primary teaching hospital of the Northwestern
University Feinberg School of Medicine. Northwestern Memorial and its
Prentice Women's Hospital and Stone Institute of Psychiatry have 897 beds
along with 1,424 affiliated physicians and 6,464 employees. Northwestern
Memorial is recognized for providing state-of-the-art patient care and
exemplary clinical and surgical advancements in the areas of cardiothoracic
and vascular care, gastroenterology, neurology and neurosurgery, oncology,
organ and bone marrow transplantation, and women's health. Northwestern
Memorial received the prestigious 2005 National Quality Health Care Award
and is listed in eight specialties in U.S. News & World Report's 2007
rankings for "America's Best Hospitals." For seven years running,
Northwestern Memorial has been rated among the nation's "100 Best Companies
for Working Mothers" by Working Mother magazine and has been chosen by
Chicagoans for more than a decade as their "most preferred hospital"
according to the National Research Corporation's annual survey.
Northwestern Memorial carries the Magnet status designation in nursing, the
highest recognition possible for patient care and nursing excellence.


Northwestern Memorial Hospital

nmh


View drug information on Gleevec.

Study Of Hip Pain And Total Hip Replacement

Osteoarthritis (OA) of the hip is a growing problem that will continue to increase as the population ages. Previous studies have reported on risk factors for developing OA, but few have examined the factors that might predict its prognosis. A new study published in the December issue of Arthritis Care & Research examined patients with hip pain to determine their disease progression and to find out how many underwent total hip replacement (THR) over the course of several years.



Led by Sita M.A. Bierma-Zeinstra and Annet M. Lievense of Erasmus Medical Center, Rotterdam, The Netherlands, the study included 227 patients who visited their general practitioners in 1996 because of hip pain. Patients were questioned about the severity of their hip pain and their general health, underwent a physical exam, had X-rays of the pelvic area and sonograms of the hip area. Three years later, the same patients underwent follow-up, during which they were interviewed in person about the progression of their hip pain and whether or not they received a THR. In addition, their OA was assessed using the WOMAC Osteoarthritis Index. After another three years, a comparable follow-up was carried out using a survey that was mailed to the patients.



The results showed that after three years, 12 percent of the patients underwent a THR because of severe pain and/or disability due to hip OA. After six years, this number increased to 36 percent. In addition, another 3 percent to 5 percent had severe pain or disability due to the condition. Being at least 60 years old, morning stiffness, pain in the groin, restricted extension and painful rotation of the hip joint were all associated with an increased risk for undergoing THR.



The researchers note that while an earlier analysis of their data did not indicate an association between age and progression of hip pain, the current study did find the two were connected. "The difference might be attributed to selection for surgery: if a patient is relatively young, physicians tend to postpone surgery to avoid the risk of re-surgery after 10-20 years," the authors point out. Earlier studies reported a connection between baseline hip pain and progression of OA, but the current study did not find this to be the case. The authors suggest this may be because all of the patients in their study already had hip pain. Also, obese patients tended to have a decreased risk of THR after three years, which may be attributable to the fact that these patients are typically advised to lose weight before undergoing the surgery.



"With information obtained from history taking, physical examination, and radiology, we are now better able to identify persons who are at high risk for progression of hip OA," the authors conclude. "This can be helpful not only to inform patients more precisely about the course of their hip pain, but also for future clinical trials."







Article:


"Prognosis of Hip Pain in General Practice: A Prospective Followup Study," Annet M. Lievense, Bart W. Koes, Jan A.N. Verhaar, Arthur M. Bohnen, Sita M.A. Bierma-Zeinstra, Arthritis Care & Research, December 2007.



Source: Amy Molnar

Wiley-Blackwell

The Unknown Risks Of Arthritis

Arthritis, in particular rheumatoid arthritis (RA), has devastating effects on the body, causing many debilitating effects and leaving many patients immobile or able to function normally. However, there are also some additional effects associated with the disease which are less well known, but just as threatening. A number of studies presented at the Annual European Congress of Rheumatology provide new data on the risks of cardiovascular diseases for RA patients, as well as some of the risks associated with the new therapies in the area, that are just beginning to emerge.



INCREASED HEART ATTACK RISKS IN RA PATIENTS DESPITE CHANGES IN DISEASE MANAGEMENT



On 23 June 2006, Dr. Ulf Bergstr?m presented the results of a study showing that, despite changes in the management of rheumatoid arthritis in the last 20 years, there is no significant impact on co-morbidity related to cardiovascular diseases, in particular, related to myocardial infarction (heart attack).



As recognized by the investigators, patients with rheumatoid arthritis (RA) have a shortened lifespan when compared to people with same gender and similar age and recent studies suggest that this is largely due to increased mortality from premature cardiovascular disease, in particular myocardial infarction. As the medical field has gained a better understanding of rheumatoid arthritis, the management of it has changed significantly in terms of medical treatments and physiotherapy.



The study evaluates the effects of the changes in management of RA on the cardiovascular morbidity and mortality in patients with established RA during 1978 to 2002, by analyzing two separate patient studies from 1978 and 1995 (with an 8 year follow-up), and compared to the corresponding background population. The study found no significant changes in the cardiovascular morbidity between the two studies (standardized mortality ratios: 158 (CI: 111-225) and 168 (CI: 118-232) for the 1978 and 1995 cohorts respectively).



"The management of the disease has changed significantly over the decades and this study gives excellent measurement into whether this has had an improvement on cardiovascular events experienced by RA patients", said Dr. Bergstr?m. "It shows that further action is necessary in order to reduce additional mortality in RA".



This study also highlights the need for further data on whether newer treatment options, such as TNF inhibitors that were introduced in Europe at the beginning of the millennium and therefore did not have a significant role in this study, will have an effect on cardiovascular events for RA patients in the future.
















TNF INHIBITORS REDUCES THE RISK OF SERIOUS CARDIOVASCULAR EVENTS IN RHEUMATOID ARTHRITIS PATIENTS



Dr. William Dixon presented the results of a new study on 23 June 2006 at the Annual European Congress of Rheumatology in Amsterdam, which shows encouraging data that treatment with TNF inhibitor reduces the risk of Myocardial Infarction (MI) and Cerebrovascular Accidents (CVA) in rheumatoid arthritis (RA) patients, when compared to patients treated with traditional DMARDs.



Recent studies suggest that the excess of deaths in rheumatoid arthritis patients is largely due to increased mortality from premature cardiovascular disease. Dr. Dixon comments, "It is already known that TNF inhibitors reduce the risk of cardiovascular events in RA patients, including less serious events. But this study has suggested that they specifically reduce the risk of myocardial infarction and cerebrovascular accidents, which are two of the most serious cardiovascular events, often leading to death". He added, "This study shows encouraging results for people with RA which could potentially reduce the mortality amongst these patients."



TNF inhibitors are a new class of drugs available for the treatment of severe rheumatoid arthritis. The drugs work by blocking the action of TNF (tumour necrosis factor), a molecule responsible for increasing levels of inflammation in people with rheumatoid arthritis. "The reason why the TNF inhibitors have shown to reduce the risk of MI and CVA could be that the events are caused by inflammatory factors, which is reduced by the TNF inhibitors' anti-inflammatory effects", said Dr. Dixon.



INCREASED RISK OF SERIOUS INFECTIONS WITH TNF INHIBITOR TREATMENT



Treatment with TNF inhibitors might increase the risk of common serious infections, according to a new study, presented at the Annual European Congress of Rheumatology in Amsterdam by Dr. Johan Askling on 23 June 2006.



As recognized by the investigators of the study, it is already established that TNF inhibitors increases the risk for intracellular infections such as TB. The risk for much more common, yet still serious, infections remains less clear. Studies from clinical practice have shown mixed results, and taken together, clinical trials indicate the possibility for a risk increase of clinical significance.



The infections that were included in the study were respiratory, septicaemia, articular, gastrointestinal, cutaneous, or other infections leading to hospitalisation.



Based on 422 hospitalizations with infection, the study concluded that, if treated with TNF inhibitors, the patients experienced a 20 to 30%-increase in risk of hospitalizations related to infections.



"The reason for this drug-related increase in risk of infections is not yet clear, although our results demonstrate a lower degree of risk increase than what was recently suggested based on trial data. However, since part of the drugs' very action is to interfere with the body's normal defense against infections, some degree of risk increase is fully conceivable", Dr. Askling said. "TNF inhibitors drugs have showed great effectiveness for many patients and is an excellent example that raises the discussion of whether, or when, the benefits the drugs outweighs any risks associated with them", Dr. Askling added.







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



Email: eularpressofficeuk.cohnwolfe



Jim Baxter

Jo Spadaccino

Mia Gannedahl



Abstract number: OP0137, OP0181, OP0182



References:


1. emedicine/radio/topic836.htm (Medicinal news from WebMD)



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

Smoking and the risk of rheumatoid arthritis

Rheumatoid arthritis (RA), like many chronic diseases of the immune system, likely results from a combination of genetic
susceptibility and environmental triggers. Recently, a team of researchers in Sweden set out to investigate the interaction
of two specific risk factors: the presence of a gene encoding protein sequence called the shared epitope (SE), the major
genetic risk factor so far defined for RA, and cigarette smoking. The results, published in the October 2004 issue of
Arthritis & Rheumatism (interscience.wiley/journal/arthritis), indicate that smoking significantly increases the
risk of RA among men and women with a genetic predisposition for the disease.


Conducted by a research team in Sweden, this population-based study focused on a large sample of patients with a confirmed
diagnosis of the disease--858 individuals, 612 women and 246 men, with an average age of 49 years. The researchers also
recruited 1,048 healthy individuals to serve as controls. Participants donated blood samples for DNA genotyping. Every
participant also completed lifestyle questionnaires, including smoking habits. Since former smokers tend to have a wide
variation in their cumulative smoking history, the researchers chose to restrict their analysis to current smokers and men
and women who had never smoked.


The DNA samples of the RA patients were studied for evidence of genes for the SE. The SE is a protein sequence found in cell
surface molecules that regulate specific immune responses. The blood samples were also tested for rheumatoid factor, a
hallmark of this disease. Then, analyzing women and men together, the researchers compared current smokers with never smokers
for the risk of rheumatoid factor positive RA. For people with the SE gene who never smoked, the increased risk for RA was
assessed at 2.8 times.


For current cigarette smokers without the SE gene, the risk factor was comparable--2.4 times. These findings affirm the SE
gene and smoking as independently related to the development of rheumatoid factor positive RA. Among current smokers with the
SE gene, however, the disease risk increased to 7.5 times. "The interaction was even more pronounced in smoking subjects with
double SE genes, whose relative risk of rheumatoid factor positive RA was 15.7 times higher," observes one of the authors
Leonid Padyukov, M.D., Ph.D. However, no risk was found for rheumatoid factor negative RA in this study.


Beyond strengthening the case against cigarette smoking as a health hazard, this study has important implications for ongoing
research into the factors contributing to RA and other autoimmune diseases. "Our study also emphasizes the need to include
data on environmental exposures in genetic analyses of a complex disease," the authors note.


Article: "A Gene-Environment Interaction Between Smoking and Shared Epitope Genes in HLA-DR Provides a High Risk of
Seropositive Rheumatoid Arthritis," Leonid Padyukov, Camilla Silva, Patrik Stolt, Lars Alfredsson, and Lars Klareskog for the
Epidemiological Investigation of Rheumatoid Arthritis Study Group, Arthritis & Rheumatism, October 2004; 50:10; pp. 3085-
3092.


This press release is also available in Swedish.



Contact: Sabina Bossi

sabina.bossiadmin.ki.se

46-8-524-838-95

Swedish Research Council

Don't Let Hand Arthritis Slow Down Your Golf Game

Arthritis can affect any joint in the body, but it can really affect your golf game when it strikes the wrists, hands and fingers. The American Society for Surgery of the Hand (ASSH) encourages individuals to educate themselves on the signs and symptoms of arthritis of the hand and seek treatment from a qualified hand specialist. Arthritis pain does not have to be permanent, and a hand specialist can get you back on the course sooner than you might think.



Osteoarthritis is a degenerative joint disease in which the cushioning cartilage that covers the bone surfaces at joints begins to wear out. It may be caused by simple "wear and tear" on joints, or it may develop after an injury to a joint. In the hand, osteoarthritis most often develops in three sites: at the base of the thumb, where the thumb and wrist come together, at the middle joint of a finger and at the joint near the finger tip. The wrist may also develop arthritis, particularly if an injury had occurred in the past. How do you know if you are suffering from osteoarthritis? Symptoms may include:



-- Stiffness

-- Pain with pinch or grip

-- Swelling and tenderness

-- Enlarged joints, nodule at the joints or cysts



What can you do if you are suffering from the symptoms of hand arthritis? Go to handcare to locate a hand specialist near you. Your physician will recommend a treatment designed to relieve pain and restore function. "Treatment decisions are based on the type of arthritis you have, its progression and its impact on your life," said Jan C. Bax, MD, PhD, an ASSH member from Appleton, Wisconsin. "Anti-inflammatory medications such as aspirin or ibuprofen may help reduce swelling and relieve pain; prescription medications or steroid (cortisone) injections may be recommended."



Your physician may refer you to a physical or occupational therapist because changing the way you do things with your hands may help relieve pain and pressure. In some cases, surgery may be the best option to relieve pain and restore useful motion.



For more information about the American Society for Surgery of the Hand and its free "Find a Hand Surgeon" service offered to the general public, please visit: handcare.



The mission of the American Society for Surgery of the Hand is to advance the science and practice of hand surgery through education, research and advocacy on behalf of patients and practitioners.



The field of hand surgery deals with both surgical and non-surgical treatment of conditions and problems that may take place in the hand or upper extremity (from the tip of the hand to the shoulder). Hand surgeons can set fractures, provide appropriate nerve care, treat common problems like carpal tunnel syndrome and tennis elbow, reattach amputated fingers, create fingers for children born with incompletely formed hands, and help people function better in their day-to-day lives through restoring use of their fingers, hands, and arms.


American Society for Surgery of the Hand

6300 North River Rd., Suite 600

Rosemont, IL 60018-4256

USA

P: 847/384-0739

F: 847/384-1435

assh

New Drug Target For Immune Diseases Discovered

Researchers from Mount Sinai School of Medicine have found a new mechanism that explains how certain immune cells are activated to create protective antibodies against infections or pathological antibodies such as those present in autoimmune diseases like lupus and rheumatoid arthritis. The research is published online in the September issue of Nature Immunology.


Autoimmune diseases like lupus and rheumatoid arthritis are characterized by exaggerated production of molecules that activate the adaptive immune system and abnormal antibodies, which attack normal cells causing inflammation and tissue damage. This exaggerated production may occur partly as a result of abnormally strong signaling from TACI via MyD88. By analyzing cells and tissues from immunodeficient patients and genetically engineered mice, Dr. Cerutti's team found a previously unknown interaction between TACI and MyD88 that is important for the production of antibodies against infectious agents. Yet, the same interaction may cause the exaggerated immune response in people with autoimmune diseases.


"Our discovery provides a novel specific target, the signaling pathway between TACI and MyD88, to block the overreaction of the immune system and tissue damage in individuals with autoimmune disorders," said Dr. Cerutti. "We look forward to studying this discovery further and developing therapeutic targets that will inhibit the interaction between TACI and MyD88, preventing autoimmune diseases from progressing with fewer side effects than currently prescribed treatments."


Dr. Cerutti's team collaborated with other researchers at Mount Sinai School of Medicine, including Charlotte Cunningham-Rundles, MD, Professor of Medicine and Pediatrics, and Huabao Xiong, PhD, Assistant Professor of Medicine.


According to the National Women's Health Information Center, autoimmune diseases impact 23.5 million Americans. Common examples include lupus, in which the immune system attacks the skin and/or several organs within the body; rheumatoid arthritis, in which the immune system attacks joints; multiple sclerosis, in which the immune system attacks the nervous system; and Type 1diabetes, in which the immune system attacks insulin-producing cells in the pancreas.


Source: The Mount Sinai Medical Center

Heart Rhythm May Be Disrupted By Popular Arthritis Drug

Celebrex, a popular arthritis drug that blocks pain by inhibiting an enzyme known as COX-2, has been shown in laboratory studies to induce arrhythmia, or irregular beating of the heart, via a novel pathway unrelated to its COX-2 inhibition.



University at Buffalo researchers discovered this unexpected finding while conducting basic research on potassium channels.



They found that low concentrations of the drug, corresponding to a standard prescription, reduced the heart rate and induced pronounced arrhythmia in fruit flies and the heart cells of rats.



The drug inhibited the normal passage of potassium ions into and out of heart cells through pores in the cell membrane known as delayed rectifier potassium channels, the study showed.



"The adverse effects of drugs like Celebrex and Vioxx based on their selective inhibition of COX-2 currently are a topic of intense discussion in the medical community," said Satpal Singh, Ph.D., associate professor of pharmacology and toxicology in the UB School of Medicine and Biomedical Sciences and senior author on the study. Vioxx was withdrawn from the market in September 2004.



"We now have shown an important new effect of Celebrex through a totally different pathway, one that is unrelated to the drug's effect as a pain reducer," Singh said. "The adverse effect arising from this unexpected mechanism definitely needs to be studied more closely, because the potassium channels inhibited by the drug are present in heart, brain and many other tissues in the human body.



The research was supported by grants from the National Science Foundation to Singh and Randall D. Shortridge, Ph.D., UB assistant professor of biological sciences, to analyze the basic properties of potassium channels.



Aware that COX-2 inhibitors had been shown to produce cardiovascular side effects, the researchers first tested whether Celebrex would affect the heart in fruit flies, a good animal system for studies on heart in other species, including humans.



"When we found an effect on the fly heart, we began looking for the underlying mechanism," said Singh. "We searched the fly genome and were surprised to find that these flies don't have cyclooxygenases, the enzymes targeted by Celebrex.



"Because the main effect of the drug in our study was induction of arrhythmia, and arrhythmia is often the result of ion-channel dysfunction," continued Singh, "we examined the drug's effect on potassium channels and other ion channels in their models and were struck by the strong inhibition of the potassium channels."



The researchers now are examining the underlying molecular mechanisms responsible for the drug's action and its effect on other ion channels that play a prominent role in setting the rhythm of the heart.
















"We are trying to determine whether the drug binds directly to the channels or to some other molecule, and if it acts by blocking the pore of the channel through which potassium ions travel or by some other mechanism," Singh said.







Results of the study appear in the Jan. 18 edition of the Journal of Biological Chemistry. Roman V. Frolov, a doctoral student working in Singh's lab, is first author on the paper. Ilya G. Berim, M.D., research scientist in the UB Department of Medicine, also is a study author, and Malcomb Slaughter, Ph.D., UB professor of physiology and biophysics and ophthalmology, made significant contributions to the research.



The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities. The School of Medicine and Biomedical Sciences, School of Dental Medicine, School of Nursing, School of Pharmacy and Pharmaceutical Sciences and School of Public Health and Health Professions are the five schools that constitute UB's Academic Health Center. The university is in full compliance with mandates of state and federal regulatory agencies pertaining to the humane use and care of research animals.



Source: Lois Baker


University at Buffalo



View drug information on Vioxx.

4SC Presents Final Phase IIa Data On Vidofludimus In Inflammatory Bowel Disease Study At The 6th ECCO IBD Conference

4SC AG (Frankfurt, Prime Standard: VSC), a drug discovery and development company focused on autoimmune and cancer indications, announces the final data from the ENTRANCE Phase IIa trial in inflammatory bowel disease (IBD) with vidofludimus, an oral inhibitor of interleukin-17 (IL-17) release and DHODH, including the secondary endpoints comprising the analysis of CDAI (Crohn's disease, CD) and CAI (ulcerative colitis, UC) disease scores, change of prednisolone intake and threshold doses, safety, pharmacokinetics and biomarkers. The data support the previously reported top-line primary endpoint result, which was achieved with a total response rate of 88.5%. These were presented last week at the 6th ECCO IBD Conference in Dublin, Ireland.


-- Primary objective of the ENTRANCE study in 26 CD and UC patients was to assess vidofludimus' remission maintenance potential in steroid-dependant IBD patients upon steroid weaning


-- Primary endpoint was met with an 88.5% total response rate (complete and partial responders), supported by secondary endpoint results demonstrating a clear clinical benefit for treated IBD patients


-- Required relapse-free prednisolone doses at the end of vidofludimus therapy were significantly lower than average doses needed prior to study entry * Average prednisolone consumption dramatically dropped over the course of the treatment period


-- Prednisolone threshold doses of partial responders at the end of the treatment were significantly reduced compared to documented threshold doses prior to study entry


-- Vidofludimus was safe and well tolerated by all patients


Entrance Trial Final Data


The top-line results from the exploratory, open-label, single-arm ENTRANCE Phase IIa study, announced in November 2010, demonstrated a 88.5% total response rate with vidofludimus versus an average placebo response rate of approximately 20% across published benchmark clinical trials, in steroid-dependant IBD patients. 53.9% (14 out of 26) of patients were complete responders, 34.6% (9 out of 26) of patients were partial responders (34.6%), and 11.5% (3 out of 26) of patients were evaluated as non-responders. No variation in response rates across the sub-disease populations of Crohn's disease (85.7%) and ulcerative colitis (91.7%) over the 12 week treatment period was observed.


CDAI/CAI disease score development was in-line with the assignment of patients to the categories complete, partial, and non-responders. All 26 evaluable patients, excluding the three non-responders, reached a relapse-free prednisolone dose which was significantly (p

Assessing The Cost Of Juvenile Arthritis

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood, yet unlike adult arthritis, little is known about its economic impact. A new study published in the February 2007 issue of Arthritis Care & Research examined direct medical costs of children with JIA and found that the economic impact was substantial.



Led by Drs. Ann Clarke, Ciaran Duffy, and Sasha Bernatsky of the McGill University Health Centre in Montreal, Quebec, the study involved 155 children with JIA and 181 controls from two hospitals in Montreal and Vancouver, Canada. Subjects' parents were given a questionnaire about the use of medications and health services during the preceding three months, without specifying any particular disease. Researchers also asked parents about time loss from their work and days missed from school for the children.



The study was the first to quantify an association between JIA disease activity and health care costs and found that the difference in annualized average direct medical costs for the JIA group versus the control group was $1,686. The JIA group also had higher costs related to specialists, health care professionals, and diagnostic tests. The authors note that the "costs were higher for JIA subjects even compared with those of clinic controls, who almost certainly had greater health resource use than the generally healthy pediatric population," adding that the controls had relatively high rates of emergency room visits, assistive devices, surgeries, and inpatient stays, probably due to the fact that some were recruited from orthopedic clinics. When comparing direct medical costs of JIA patients with recent cost estimates for asthma, JIA appeared to be more costly, mostly because of higher medication costs.



The current study does not quantify the long-term medical and social costs of having inadequately controlled arthritis in childhood. "Ongoing active inflammation and the consequent joint damage have a significant impact on the ability of an individual to be a productive member of society," the authors state. They note that the JIA patients on average had more missed days of school per year compared with the controls and point out that indirect costs, such as missed time from work, are also very important from a societal perspective.



Insight into factors that influence health care costs can play an important role in resource allocation, which is increasingly important in light of economic constraints on health care systems, the authors state.



The results of the study are important in helping to quantify the magnitude of health care cost savings that could result in better disease control, especially given the development of costly new medications, the authors state. "Ultimately, decisions regarding access to therapies should be considered in terms of overall cost-benefit ratios," they conclude. "More effective interventions, even if associated with higher initial health care costs, may well have significant long-term cost savings to society."







Article: "Economic Impact of Juvenile Idiopathic Arthritis," Sasha Bernatsky, Ciaran Duffy, Peter Malleson, Debbie Ehrmann Feldman, Yvan St. Pierre, Ann E. Clarke, Arthritis Care & Research, February 2007; (DOI: 10.1002/art.22463).



Contact: Amy Molnar


John Wiley & Sons, Inc.

"ACTEMRA®" Humanized Anti-Human IL-6 Receptor Monoclonal Antibody Conditions For Approval (All Patients Surveillance) Lifted In Japan

Chugai Pharmaceutical Co., Ltd. announced today that it has received a notification from the Japanese Ministry of Health, Labour and Welfare (MHLW) that the conditions for approval (surveillance of all patients) are lifted with "rheumatoid arthritis(RA)" and "polyarticular-course juvenile idiopathic arthritis (pJIA)" indications for the humanized anti-human IL-6 receptor monoclonal antibody, ACTEMRA®.


For ACTEMRA®, additional approval of indications of "RA (including prevention of structural damage of joints)," "pJIA" and "systemic-onset juvenile idiopathic arthritis (sJIA)" was obtained in April 2008. As one of the conditions for this approval, it had been required that "data on the safety and efficacy of this drug shall be swiftly collected by conducting surveillance of uses in all patients and that the necessary measures shall be taken for the proper use of the drug until data on a certain number of patients is accumulated after marketing."



Data on 3,987 patients with RA and pJIA was submitted to the Japanese MHLW as the interim analysis results of the above surveillance. Based on the results, it has been determined that there is no problem necessitating additional measures for the safety and efficacy of this drug at this time. Accordingly, the conditions for approval involving the all patient surveillance have been lifted. For the surveillance, over 10,000 patients have been enrolled up to date. The final analysis of safety data will be done on the 8,300 patients enrolled by November 15, 2009, and will be reported as soon as they become available.


Among the indications of this drug, surveillance of all patients with sJIA and Castleman's disease is still conducted and new patients continue to be enrolled.



ACTEMRA®, the first antibody drug (humanized monoclonal antibody) originating from Japan, was created by Chugai in collaboration with Osaka University, utilizing genetic recombinant technology to produce a monoclonal antibody against the anti-IL6 receptor. It works by inhibiting biological activity of IL-6 through competitively blocking the binding of IL-6 to its receptor.


Rheumatoid arthritis is a systemic inflammatory disease that mainly causes progressive and multiple joint destructions, for which the cause is unknown. It appears more commonly in females in their 40s and 50s, and the disease is causing serious psychological and social problems not only for the patients but also for their families, and measures to counter the disease are seriously needed. Patients are often forced to spend a long time fighting the disease, causing various difficulties in social life such as school life and employment.



Chugai focuses on bone and joint diseases area as one of the strategic domains, and hopes to contribute to the treatment by providing innovative therapeutic options for patients and medical professionals. The company will continue to make efforts for promoting the proper use and supplying information while giving the highest priority to the safety of patients.


Source: Chugai


View drug information on Actemra.

Rheumatoid Arthritis Patients Benefit From Enbrel In Combination With Methotrexate

Rheumatoid arthritis patients who are on standard methotrexate therapy may benefit from the addition of the biologic treatment, Enbrel* (etanercept), according to new data from a one-year, open-label extension of the international TEMPO trial. The study results, presented this week at the European League Against Rheumatism (EULAR), 2006, also showed that the safety profile and clinical efficacy of Enbrel and methotrexate combination therapy were sustained at four years of treatment.1


The TEMPO extension trial was an open-label 52-week study involving subjects who had completed the 3-year double-blind TEMPO trial. At the end of the 3-year TEMPO trial, 227 subjects who met the specific predefined criteria continued into the 1-year, open-label extension. All subjects received treatment with the combination of Enbrel and methotrexate. Subjects receiving methotrexate monotherapy during the 3-year double-blind TEMPO trial were switched to the combination of Enbrel and methotrexate (n = 55). Subjects receiving Enbrel monotherapy during the 3-year double-blind TEMPO trial were switched to the combination of Enbrel and methotrexate (n = 76). Subjects receiving combination therapy during the 3-year double-blind TEMPO trial were continued on the same regimen (n = 96).


Commenting on the implications of the results, Professor Robert Moots, Professor of Rheumatology at the University of the Liverpool said: "These latest data show for the first time that the efficacy of combination treatment with methotrexate and Enbrel can be sustained for up to four years. This is encouraging news for rheumatoid arthritis patients who are currently on this regimen, or for patients who are discussing potential treatment choices with their consultant."


The results of the 227 patient one-year open-label extension of the TEMPO study show that the combination therapy with ENBREL and methotrexate demonstrated clinical improvement and was well-tolerated during the one-year study.1 Fifty per cent of patients taking ENBREL and methotrexate for four years achieved clinical remission based on the disease activity score (DAS)* of less than 1.6, the primary clinical efficacy endpoint, compared with 38.7 per cent at three years.1 Seventy-four per cent of patients taking ENBREL and methotrexate for four years achieved a DAS of less than 2.4 (low disease activity) compared with 66.7 per cent at three years.1 In addition, the data also demonstrate that among the rheumatoid arthritis patients treated with methotrexate monotherapy for three years, whose mean disease activity was moderate, the addition of ENBREL provided further improvement in clinical efficacy that approached the response achieved by patients treated with combination therapy for four years (mean DAS 1.9 vs. 1.8, respectively).1 The addition of methotrexate to patients who received ENBREL monotherapy for three years also resulted in improvements at four years (mean DAS 2.2)1. The proportions of subjects achieving clinical remission by adding ENBREL to methotrexate and adding methotrexate to ENBREL at four years were 41.8% and 38.2% and were not statistically different from each other nor compared to the combination group.1















Ailsa Bosworth, chief executive, National Rheumatoid Arthritis Society, UK said, "Rheumatoid arthritis is a painful and debilitating disease that has consequences not only for people with the condition but also for their families, friends and employers. It is vital that people with rheumatoid arthritis have access to treatments that have been proven effective to inhibit the progression of joint damage and to improve physical function."


Although there have been a relatively small number of studies reporting on prevalence, these studies show that rheumatoid arthritis affects approximately 0.5 to one per cent of the adult population in developed populations, and about twice as many women as men suffer from the disease.2 Patients with rheumatoid arthritis experience inflammation, and morning stiffness, usually in the small joints of the hands and feet and often symmetrically. As the disease progresses, irreversible joint damage may lead to limited motion and loss of function. Rheumatoid arthritis can be a devastating disease that can negatively affect quality of life and may result in increased feelings of depression. During the first three years of the disease, 20 to 30 per cent of patients become permanently work disabled. Within 10 years of diagnosis, almost 50 per cent of patients are unable to work.


*DAS


DAS is a combined index to measure disease activity in rheumatoid arthritis patients and is a validated tool used in clinical trials and serves as the basis for the EULAR response criteria.


ENBREL


In the European Union, Enbrel is approved alone or in combination with methotrexate for the treatment of active rheumatoid arthritis in adults when the response to disease-modifying antirheumatic drugs, including methotrexate (unless contraindicated), has been inadequate. Enbrel is also indicated in the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. In patients with rheumatoid arthritis, Enbrel used alone or in combination with methotrexate has been shown to slow the progression of disease-associated structural damage as measured by X-ray .


Enbrel is given by injection and the recommended dosing is 25 mg twice weekly for all adult rheumatology indications8.


Since the product was first introduced, serious infections, some involving death, have been reported in patients using Enbrel. Patients should tell their doctor if they currently have an infection or are prone to getting infections. Patients should not start Enbrel if they have an infection of any type or an allergy to Enbrel or its components. Enbrel should be used with caution in patients prone to infection8.


The most frequent adverse event in clinical trials in rheumatoid arthritis patients were injection-site reactions (ISRs) (36%)8.


Enbrel acts by binding tumor necrosis factor (TNF), one of the dominant inflammatory cytokines or regulatory proteins that play an important role in both normal immune function and the cascade of reactions that causes the inflammatory processes of rheumatoid arthritis. The binding of Enbrel to TNF renders the bound TNF biologically inactive, which can result in reduction of inflammatory activity8.


WYETH


Wyeth Pharmaceuticals, a division of Wyeth (NYSE:WYE), has leading products in the areas of women's health care, cardiovascular disease, central nervous system, inflammation, transplantation, haemophilia, oncology, vaccines and nutritional products. Wyeth has a diverse portfolio of biopharmaceutical products and is currently marketing seven of these products. Wyeth is one of the world's largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing, and marketing of pharmaceuticals, vaccines, biotechnology products and nonprescription medicines that improve the quality of life for people worldwide. The Company's major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare, and Fort Dodge Animal Health.


CSR-64179 An open-label, multicentre, extension study of the combination of etanercept and methotrexate in rheumatoid arthritis subjects. 11 May 2006

Gabriel SE. The epidemiology of rheumatoid arthritis. Rheum. Dis. Clin. North Am. 2001;27:269-281

Harris ED Jr. Rheumatoid arthritis: pathophysiology and implications for therapy. N Engl J Med. 1990;322:1277-1289

Fuchs HA, Sergent JS. Rheumatoid arthritis: the clinical picture. In: Koopman WJ, ed. Arthritis and Allied Conditions: A Textbook of Rheumatology. 13th ed. Baltimore, Md: Williams & Wilkins: 1997;1:1041-1065

Schned ES, Reinertsen JL. The social and economic consequences of rheumatic disease. In: Klippel JH, ed. Primer on Rheumatic Diseases. 11th ed. Atlanta, Ga: Arthritis Foundation; 1997:6-9

Sokka T. Work disability in early rheumatoid arthritis. Clin Exp Rheumatol. 2003 Sep-Oct;21(5 Suppl 31):S71-4.

Yelin E, Henke C, Epstein W. The work dynamics of the person with rheumatoid arthritis. Arthritis Rheum. 1987 May;30(5):507-12.

Enbrel (etanercept) SmPC. Last updated 21 September 2005. Accessed from Electronic Medicines Consortium (accessed 19 June 2006)


wyeth


View drug information on Enbrel.

Mayo Collaboration Finds Source Of Breast Drug Side Effect

Mayo Clinic researchers and their international colleagues have discovered genetic variants that lead to severe arthritis for a subset of women when taking aromatase inhibitors to treat their breast cancer. This serious side effect is so painful that many women halt their lifesaving medication. The findings appear in the online issue of Journal of Clinical Oncology.


"Many women stop taking aromatase inhibitors due to the accompanying joint pain," says James Ingle, M.D., Mayo Clinic oncologist and senior author of the study. "We used the latest genetic technology in a very large group of women and discovered totally new clues to the cause of the main reason women stop this potentially lifesaving drug. Our findings open the door to finding ways to identify women who will develop these side effects and treat those who do, thus allowing more women to take this therapy and decrease their chances of breast cancer recurrence." Aromatase inhibitors are most often used as adjuvant therapy for postmenopausal women with early stage breast cancer.


How the Research Was Conducted


The researchers -- including investigators from the United States, Canada and Japan -- conducted a genome-wide association study to identify gene variants called single nucleotide polymorphisms (SNPs) that are associated with musculoskeletal pain. They selected patients who were enrolled in a prospective clinical trial, MA27, conducted by the NCIC Clinical Trials Group in Canada in collaboration with the NCI-sponsored North American Breast Cancer Groups comparing two aromatase inhibitor drugs. Two controls were matched with each patient and each patient who was selected experienced arthritis-like side effects within the first two years of treatment, or had already dropped out of the trial because of the pain. Researchers studied 293 separate cases, comparing them to 585 controls.


They found four likely SNPs on chromosome 14, all of which were nearest the gene T-Cell Leukemia 1A, which they discovered also was estrogen dependent. One of the SNPs also created an estrogen response with increased gene expression after exposure to estradiol, a widely used post-menopausal treatment. The results provide researchers with genetic markers for the aromatase inhibitor-induced arthritis and clues to find ways to treat it.


Support for the study came from the National Institutes of Health (NIH), the Canadian Cancer Society, the Biobank Japan Project funded by the Ministry of Education, Culture, Sports, Science and Technology, and the Breast Cancer Research Foundation. Other support was provided by the NIH Pharmacogenomics Research Network and the RIKEN Center for Genomic Medicine Global Alliance. The trial mentioned in the study was supported in part by Pfizer, Inc.


Other researchers include Daniel Schaid, Ph.D., Gregory Jenkins, Anthony Batzler, Mohan Liu, Ph.D., Liewei Wang, M.D., Ph.D., Matthew Goetz, M.D., and Richard Weinshilboum, M.D., all of Mayo Clinic; Paul Goss, M.B., BCh, Ph.D. Massachusetts General Hospital Cancer Center, Harvard University; Taisei Mushiroda, Ph.D., Michiaki Kubo, M.D., Ph.D., and Yusuke Nakamura, M.D., Ph.D., RIKEN Center for Genomic Medicine, Tokyo; Judy-Anne Chapman, Ph.D., Lois Shepherd, M.D., and Joseph Pater, M.D., NCIC Clinical Trials Group, Kingston, Ontario; Matthew Ellis, M.B., B.Chir., Ph.D., Washington University, St. Louis; Vered Stearns, M.D., John Hopkins School of Medicine, Baltimore; Daniel Rohrer, M.D., Ohio State University Medical Center, Columbus; Kathleen Pritchard, M.D., Sunnybrook Odette Regional Cancer Centre, University of Toronto; and David Flockhart, M.D., Ph.D., Indiana University, Indianapolis.


Source: Mayo Clinic


View drug information on Estradiol Transdermal System.

Sydney Scientists Discover And License Breakthrough Anti-inflammatory Treatment

Scientists from the Garvan Institute of Medical Research have developed what could be the next big blockbuster treatment for inflammatory diseases such as rheumatoid arthritis and asthma.



This discovery is being commercialised by G2 Therapies Ltd, a biotechnology company founded by Garvan, which today announced the signing of an AU$135 million research, development and licensing agreement with Danish healthcare company, Novo Nordisk. The terms of the agreement include an upfront payment and other success-based payments to a potential total of around US$100 million (A$135 million), plus royalties on commercialised therapeutics. The partnership will enable the new therapy to be taken through to human clinical trials.



Professor Charles Mackay, Head of Garvan's Arthritis & Inflammation Program and founder of G2 Therapies, says: "We have done what many others have been trying to do for years. We have made a therapeutic antibody against one of the most potent inflammatory agents in the body and used it to cure arthritis in mice. The next step is to translate the highly effective outcome we see in mice to human patients. If we can do this, we will have a revolutionary new treatment for a number of important human diseases".



The body needs a certain amount of inflammation to protect itself against disease. The hallmarks of inflammation reflect the major events: swelling of localised blood capillaries, and the movement of fluid and immune cells into damaged tissue in an effort to contain infection.



When immune cells become overactive, as is the case with rheumatoid arthritis, too many of them move into damaged tissue and exacerbate the condition. The new antibody blocks the action of one of the most important molecules for guiding inflammatory cells into tissue.



"We anticipate that our antibody will be a significant improvement over current therapies because it acts at a different and earlier point in the inflammatory process compared with current anti-inflammatory therapies," says Mackay.



Rheumatoid arthritis (RA) alone affects more than 21 million people worldwide and causes swelling of major joints, severe pain, and fatigue. In addition to treating RA, Professor Mackay believes their therapeutic could also be used for psoriasis, sepsis, heart attack and transplant patients.



Professor John Shine FAA AO, Executive Director of the Garvan Institute says: "It is important to work with companies if we are to turn scientific discoveries into real patient benefits. The Garvan's commitment to taking our research from bench to bedside is evidenced by our investment in companies such as G2 and encouraging our senior scientists to participate in the commercialisation of research".
















The Novo Nordisk licensing agreement has a potential value of over US$100 million (A$135 million), making it one of the largest licensing agreements ever secured by an Australian biotechnology company. Going forward, the Garvan Institute and G2 will remain involved in the crucial stages of development, making the deal one of the few true partnerships between academia and industry.



Commenting on the deal, Mr Bill Ferris AO, Chairman of the Garvan Institute's Board, says: "This is an exciting example of what is possible when you back early stage research with venture capital and encourage discoveries to develop in-house. Facilitating venture capital investment in medical research will ensure that all Australians will benefit from home-grown medical advances like the new anti-inflammatory treatment that has been developed at the Garvan."







NOTES FOR EDITORS:



Garvan's Arthritis and Inflammation program is supported by the National Health and Medical Research Council (NHMRC).



G2's development and commercialisation activities were supported by two Commonwealth programs administered by AusIndustry: Biotechnology Innovation Fund (BIF) and R&D Start (now collectively replaced by the Commercial Ready program), as well as grants from NSW Department of State and Regional Development (Proof of Concept and Non-Research Establishment Cost grants).



The Garvan Institute of Medical Research has a long-standing relationship with Novo Nordisk, principally in diabetes research.



About Garvan

The Garvan Institute of Medical Research was founded in 1963 by the Sisters of Charity. Initially a small research department of St Vincent's Hospital in Sydney, it is now one of Australia's largest medical research institutions with over three hundred scientists, students and support staff. The Garvan Institute's main research programs are: Arthritis & Inflammation, Osteoporosis, Cancer, Diabetes & Obesity, and Neuroscience.



About G2 Therapies

G2 Therapies is a biotechnology company founded in 2002 based on research undertaken by two scientists from the Garvan Institute of Medical Research, Professor Charles Mackay and Professor Rob Sutherland, with the aim of developing and commercialising antibody based therapeutics in inflammation and cancer. G2 is based at the Garvan Institute in Sydney, Australia, and conducts its research through two operating subsidiaries, G2 Inflammation P/L and G2 Cancer P/L. G2 Therapies is a private company chaired by Dr John Schubert, and its major investors include AMWIN, Baron Nominees, and the Garvan Institute of Medical Research. For further information, visit g2therapies.au/.



About Novo Nordisk

Novo Nordisk is a healthcare company and a world leader in diabetes care and biopharmaceuticals. Novo Nordisk manufactures and markets pharmaceutical products and services that make a significant difference to patients, the medical profession and society. With headquarters in Denmark, Novo Nordisk has more than 22,000 full-time employees in 79 countries, and markets its products in 179 countries. Novo Nordisk's B shares are listed on the stock exchanges in Copenhagen and London. Its ADRs are listed on the New York Stock Exchange under the symbol 'NVO'. Novo Nordisk sales for 2005 were over A$7.3 billion. For more information, visit novonordisk/.



Contact: Branwen Morgan

Research Australia

Health Canada Approves SIMPONI(TM) (golimumab) For Treatment Of Rheumatoid Arthritis, Psoriatic Arthritis And Ankylosing Spondylitis

Centocor Ortho Biotech Inc. and Schering-Plough Corporation (NYSE: SGP) announced that Health Canada has granted approval of SIMPONI (TM) (golimumab) as a once-monthly, subcutaneous therapy for the treatment of moderately to severely active rheumatoid arthritis (RA), active psoriatic arthritis (PsA) and active ankylosing spondylitis (AS). With this approval in Canada, SIMPONI, in combination with methotrexate (MTX), is indicated for reducing the signs and symptoms in adult patients with moderately to severely active RA; reducing signs and symptoms in adult patients with moderately to severely active PsA, alone or in combination with MTX; and reducing signs and symptoms in adult patients with active AS who have had an inadequate response to conventional therapies. SIMPONI is the first biologic therapy to be approved concurrently in three distinct rheumatologic diseases. Schering-Plough anticipates that the medication will become available in Canada in the second half of 2009.


"This first approval marks a major milestone in the clinical development program for SIMPONI," said Jerome A. Boscia, M.D., senior vice president, Clinical R&D, Centocor Research & Development, Inc. "More importantly, the approval of SIMPONI expands the therapeutic options for physicians and offers patients an effective new medication that can be self-administered once monthly."


"This is the first approval for SIMPONI, one of the five stars in our late-stage pipeline," said Thomas P. Koestler, Ph.D., executive vice president, Schering-Plough Corporation and president, Schering-Plough Research Institute. "Offering once-monthly subcutaneous dosing, SIMPONI will provide an important and convenient new treatment option to rheumatologists and their patients. SIMPONI expands our leading immunology franchise in meeting the needs of the rheumatology community."


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


In March 2008, Centocor Ortho Biotech Inc. and Schering-Plough Corporation announced that a Marketing Authorization Application (MAA) had been submitted to the European Medicines Agency (EMEA) requesting the approval of golimumab as a monthly subcutaneous treatment for adults with RA, PsA and AS.















In June 2008, Centocor Ortho Biotech Inc. announced that a Biologics License Application (BLA) had been submitted to the U.S. Food and Drug Administration (FDA) requesting the approval of golimumab as a monthly subcutaneous treatment for adults with active forms of RA, PsA and AS.


The approval of SIMPONI in Canada is based on data from five pivotal clinical trials: GO-BEFORE, GO-FORWARD, GO-AFTER, GO-REVEAL and GO-RAISE. Each trial found SIMPONI to be effective in reducing the signs and symptoms of RA, PsA and AS.


About Rheumatoid Arthritis


RA is a chronic and debilitating disease that affects approximately 4 million people in Canada. Signs and symptoms of RA include pain, stiffness and motion restriction in multiple joints. Because RA is a progressive disease, over time it can cause permanent joint deformity and severe disability. 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 Psoriatic Arthritis Psoriatic arthritis is a chronic inflammatory arthropathy manifesting with joint pain and swelling that can lead to joint destruction and debilitation over time. It is frequently associated with inflamed, scaly, red patches of skin psoriasis and psoriasis nail involvement. Symptoms may include stiffness and tenderness of the joints and surrounding tissue and reduced range of motion. Joints of the hands, wrists, knees, ankles, feet, lower back and neck are commonly affected. Psoriasis affects an estimated two to three percent of the world's population, and approximately one out of three patients affected by psoriasis may develop psoriatic arthritis. Both men and women are equally affected by psoriatic arthritis, most commonly between the ages 30 and 50, in the peak of their productive years.


About Ankylosing Spondylitis


Ankylosing spondylitis is a painful and progressive form of spinal arthritis, and symptoms of inflammatory back pain often first present in people under the age of 35 years. It typically begins in the late teens and early twenties, and in severe cases can result in fusing of the spinal vertebrae and cause structural damage to hips and other joints. Often misdiagnosed as "just back pain" or undifferentiated arthritis, ankylosing spondylitis is a systemic inflammatory disease that, in addition to its effect on the spine, can affect internal organs, peripheral joints and vision.


About SIMPONI


SIMPONI is a human monoclonal antibody that targets and neutralizes excess TNF-alpha, a protein that when overproduced in the body due to chronic inflammatory diseases can cause inflammation and damage to bones, cartilage and tissue. The first once-monthly subcutaneous anti-TNF-alpha therapy, SIMPONI is approved in Canada for the treatment of moderately to severely active rheumatoid arthritis, active psoriatic arthritis and active ankylosing spondylitis, and is available either through the SIMPONI SmartJect auto injector or a prefilled syringe. SIMPONI is also being studied as an intravenous infusion therapy for the treatment of rheumatoid arthritis.



In Canada, SIMPONI is approved for:


-- In combination with methotrexate (MTX), reducing signs and symptoms in
adult patients with moderately to severely active rheumatoid arthritis.


-- Reducing signs and symptoms in adult patients with moderately to
severely active psoriatic arthritis, alone or in combination with MTX.
SIMPONI can be used in combination with MTX in patients who do not
respond adequately to MTX alone.


-- Reducing signs and symptoms in adult patients with active ankylosing
spondylitis who have had an inadequate response to conventional
therapies.


Important Safety Information


SIMPONI is contraindicated in patients with severe infections such as sepsis, tuberculosis and opportunistic infections and in patients who are hypersensitive to golimumab, latex or any of the excipients. Serious infections, including sepsis, pneumonia, tuberculosis, invasive fungal and other opportunistic infections have been observed with the use of TNF antagonists including SIMPONI. Some of these infections have been fatal. SIMPONI should not be given to patients with a clinically important, active infection (chronic or localized). Caution should be exercised when considering the use of SIMPONI in patients with a chronic infection or a history of recurrent infection. Patients should be monitored for signs and symptoms of infection while on or after treatment with SIMPONI. If a patient develops a serious infection or sepsis, SIMPONI therapy should be discontinued. Patients should be advised of and avoid exposure to potential risk factors for infection as appropriate. For patients who have resided in or traveled to regions where invasive fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic, the benefits and risks of SIMPONI treatment should be carefully considered before initiation of SIMPONI therapy. Patients must be evaluated for the risk of tuberculosis, including latent tuberculosis, prior to initiation of SIMPONI. Treatment of latent tuberculosis infection should be initiated prior to therapy with SIMPONI. Antituberculosis therapy prior to initiating SIMPONI should also be considered in patients who have several or highly significant risk factors for tuberculosis infection and have a negative test for latent tuberculosis. Patients receiving SIMPONI should be monitored closely for signs and symptoms of active tuberculosis during and after treatment, including patients who tested negative for latent tuberculosis infections. The use of TNF blocking agents has been associated with reactivation of hepatitis B virus in patients who are chronic carriers of the virus. Chronic carriers of hepatitis B should be appropriately evaluated and monitored prior to the initiation of, during treatment with, and for several months following discontinuation of SIMPONI.


Lymphomas have been observed in patients treated with TNF blocking agents, including SIMPONI. The incidence of non-lymphoma malignancies was similar to controls, and lymphoma is seen more often than in the general population. The potential role of TNF-blocking therapy in the development of malignancies is not known. Caution should be exercised when considering TNF-blocking therapy for patients with a history of malignancy or when considering continuing treatment in patients who develop malignancy.


Worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. Cases of CHF in patients with known cardiovascular risk factors have been observed with SIMPONI. SIMPONI should be used with caution in patients with heart failure and should be discontinued if new or worsening symptoms of heart failure appear. TNF-blocking agents, including SIMPONI, have been associated in rare cases with demyelinating disease. The benefits and risks of anti-TNF treatment should be carefully considered before initiation of SIMPONI therapy in patients with pre-existing or recent onset of demyelinating disorders. Treatment with SIMPONI may result in the formation of auto-antibodies and, rarely, in the development of a lupus-like syndrome. Women of childbearing potential must use adequate contraception to prevent pregnancy and continue its use for at least 6 months after the last SIMPONI treatment.


The most common adverse drug reaction reported from clinical trials was upper respiratory tract infection (7.2 percent of SIMPONI-treated patients compared with 5.8 percent in control-treated patients). In controlled Phase 3 trials through Week 16 in RA, PsA and AS, 5.8 percent of SIMPONI treated patients had injection site reactions compared with 2.2 percent in control-treated patients. The majority of the injection site reactions were mild and moderate, and the most frequent manifestation was injection site erythema.


About Centocor Ortho Biotech Inc.


Centocor Ortho Biotech Inc. redefines the standard of care in immunology, nephrology, and oncology. The company was created when Ortho Biotech Inc. merged into Centocor, Inc., and Centocor, Inc. was renamed Centocor Ortho Biotech Inc. Built upon a pioneering history, Centocor Ortho Biotech Inc. harnesses innovations in large-molecule and small-molecule research to create important new therapeutic options. Beyond its innovative medicines, Centocor Ortho Biotech is at the forefront of developing education and public policy initiatives to ensure patients and their families, caregivers, advocates, and healthcare professionals have access to the latest treatment information, support services, and quality care. Centocor Ortho Biotech is a wholly-owned subsidiary of Johnson & Johnson.


(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 Ortho Biotech Inc. and/or Johnson & Johnson'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 28, 2008. Copies of this Form 10-K, as well as subsequent filings, are available online at sec, jnj or on request from Johnson & Johnson. Neither Centocor Ortho Biotech Inc. nor Johnson & Johnson 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.


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 SIMPONI.


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 1A. "Risk Factors" in Schering-Plough's 2008 10-K, filed February 27, 2009.


SIMPONI (TM) is the trademark of Centocor Ortho Biotech Inc. used under license by Schering-Plough Canada Inc.


Source: Schering Plough


View drug information on Simponi.