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Newswise — Data to be presented at the 71st annual meeting of the American College of Rheumatology (ACR) showed that when over-the-counter (OTC) naproxen sodium, commercially sold as Aleve, was added to an aspirin therapy regimen, there was no change in platelet aggregation measures versus baseline. Unlike ibuprofen, which can negate the intended cardiovascular benefit of aspirin therapy, an OTC dose of naproxen sodium did not change the antiplatelet effect profile seen with aspirin therapy alone.

The aggregation or accumulation of platelets can cause clotting in the arteries, which can lead to a heart attack or ischemic stroke. It has been reported that one in five Americans (an estimated 43 million) regularly take aspirin and globally, it is estimated that more than 90 million are taking aspirin for cardioprotection. Taken regularly, low-dose aspirin can help prevent one out of three heart attacks. However, the U.S. Food and Drug Medicine hat news paper
(FDA) has recently mandated that ibuprofen products now carry a warning that there may be an interaction between ibuprofen and aspirin, which might render aspirin therapy less effective when used for its antiplatelet, cardioprotective effect.

This study is good news for the millions of Americans who currently use low-dose aspirin therapy, and also need safe, over-the-counter pain relief for general aches and pains, including the minor pain of arthritis. These results tell us that Aleve doesnt interfere with aspirin the way some other analgesic treatments may, giving the consumer more freedom to make choices about pain relief without worrying about this drug interaction, said study author Michael Schiff, M.D., of the Denver Arthritis Clinic.

This research explored the effect of OTC doses of naproxen sodium (220 mg tid) or acetaminophen (1,000 mg qid) on the antiplatelet effect when administered together with low-dose aspirin therapy (81mg). Acetaminophen was used as a comparator as previous research has confirmed that it does not alter the platelet inhibition of low dose aspirin therapy. This clinical study did not measure the degree of molecular interaction, but the findings suggest that those on aspirin therapy can safely take OTC naproxen without compromising the intended cardiovascular benefit of aspirin. The findings will be presented via poster presentation on Friday, November 9.

These results are consistent with previous findings on the prescription dose of naproxen. Results of a previous study indicated that the prescription strength dose of naproxen (500mg bid) administered two hours before or after low-dose aspirin did not interfere with the anitplatelet effects.

Methodology and Findings

This study was a single-center, randomized, open-label, 3-period trial with an intent-to-treat (ITT) population of 45 healthy men and women. Thirty seven participants who met the study criteria were given 81 mg of enteric-coated, low-dose aspirin once daily. After the first five days, all subjects demonstrated a 99 percent level of thromboxane (TXB2) inhibition.

The group was then divided into three groups for an additional five days of treatment:
The first group n=12 continued on 81 mg of enteric-coated, low-dose aspirin once daily;
The second group n=12 were given 81 mg of enteric-coated, low-dose aspirin once daily plus naproxen 220 mg three times daily; and
The third and final group n=13 were given 81 mg of enteric-coated, low-dose aspirin once daily plus 1,000 mg of acetaminophen four times daily.

After the second round of treatment, all arms showed a 99% or higher thromboxane inhibition, supporting the conclusion that naproxen sodium does not change the antiplatelet effect profile seen with aspirin alone. The primary endpoint in the study was the inhibition of TXB2, measured through blood samples that were collected after the first five days of the study and again on day 11. The mean (SD) degree of serum TXB2 inhibition was:
99.7% ( 0.26%) for 81 mg of enteric-coated, low-dose aspirin once daily
99.7% ( 0.26%) for 81 mg of enteric-coated, low-dose aspirin once daily plus naproxen 220 mg three times daily
99.6% ( 0.45%) for 81 mg of enteric-coated, low-dose aspirin once daily plus 1,000 mg of acetaminophen four times daily

An exploratory endpoint in which researchers evaluated thromboxane inhibition of those who discontinued naproxen sodium but continued to receive 81 mg of enteric-coated low-dose aspirin requires additional evaluation before conclusions can be drawn.

These data, confirming that the OTC dose of naproxen sodium did not interfere with daily doses of 81mg aspirin, add to the significant body of evidence that support the cardiovascular safety of naproxen, said study author Marc C. Hochberg, M.D., M.P.H., Professor of Medicine and Head of the Rheumatology and Clinical Immunology Division, University of Maryland School of Medicine.

About ALEVE and ALEVE Liquid Gels

Since its introduction as an OTC product in June 1994, ALEVE has been used by millions of Americans as a safe and effective pain reliever for more than a decade. ALEVE Liquid Gels, launched in March 2007, were developed to provide liquid-fast relief. With the convenience of all day relief with just two pills, ALEVE and ALEVE Liquid Gels can be used for the treatment of aches and pains due to minor arthritis pain, muscle aches, backache, headache, toothache, menstrual pain and pain associated with the common cold. Always read and follow label instructions.

ALEVE and ALEVE Liquid Gels are available at food, drug and mass retail outlets nationwide. For more information, visit www.ALEVE.com.

About Bayer Consumer Care

The Consumer Care Division of Bayer HealthCare LLC, is medicine in Morristown, N.J. Bayers Consumer Care Division is among the largest marketers of over-the-counter medications and nutritional supplements in the world. Some of the most trusted and recognizable brands in the world today come from the Bayer portfolio of products. These include Bayer Aspirin, ALEVE, Flanax/Apronax, Alka-Seltzer Plus, Bactine, RID, Phillips Milk of Magnesia, Midol, Alka-Seltzer, Talcid, Rennie, Canesten, Bepanthen, Bepanthol, One-A-Day vitamins, FlintstonesTM vitamins, Supradyn, Redoxon, Berocca, Cal-D-Vita/Elevit, Vital 50 Plus, Medicine hat news.

Bayer HealthCare, a subsidiary of Bayer AG, is one of the world’s leading, innovative companies in the health care and medical products industry based in Leverkusen/Germany. In 2006, the Bayer HealthCare subgroup generated sales amounting to some 11.7 billion Euro. The company combines the global activities of the divisions Animal Health, Consumer Care, Diabetes Care and Pharmaceuticals. Since January 1, 2006 the new Pharmaceutical Division consists of the former Biological Products and Pharmaceutical Division and now comprises three business units: Hematology/Cardiology, Oncology and Primary Care. Bayer HealthCare’s aim is to discover and manufacture innovative products that will improve human and animal health worldwide. The products enhance well-being and quality of life by diagnosing, preventing and treating diseases.

Newswise — Denosumab treatment every six months can reduce bone erosions in patients with rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Boston, Mass.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 2.1 million Americans have RA, most of them women.

Denosumab is a fully human monoclonal antibody which attaches to, and inhibits, a molecule in the bone called RANK ligand. RANK ligand is important in the function of osteoclasts, the cells responsible for bone resportion. If overproduced in the body, RANK ligand can cause bone loss, including bone erosions in rheumatoid arthritis.

Researchers conducted a study to determine if denosumab treatment could reduce the progression of bone erosions in patients with rheumatoid arthritis taking methotrexate.

A total of 227 patients were randomly assigned in this double-blind, placebo-controlled study and received subcutaneous injections of 60 or 180 mg of denosumab or placebo every six months.

To assess progress, X-rays were taken of hands and feet at the beginning of the study and at six months and 12 months into the study. By using a standard scoring system to measure damage to joints by x-ray, erosions and joint space narrowing were evaluated and monitored throughout the study.

Eighty-nine percent of the participants completed the 12 month study. Medicine hat news classifieds
taking denosumab (at both 60 and 180 mg) showed decreased progression of bone erosions compared with the placebo group; this effect was already discernable by six months for the higher dose group. However, there was no detectable difference in joint space narrowing between the groups, and the data for cartilage turnover suggested that the dose and frequency used in the study may not have been sufficient to preserve cartilage.

The erosion scores after six months from the standard x-rays were consistent with erosion scores seen by magnetic resonance imaging studies. Adverse events were similar across all three treatment groups.

These data show the significant potential of denosumab, revealing that patients receiving denosumab experienced a reduced progression of erosions compared to control, said Dsire van der Heijde, MD, PhD; professor of rheumatology; dept of rheumatology; Leiden University Medical Center; The Netherlands. Most significant was the difference observed between the control group and the group receiving denosumab 180mg. The reduction in progression of erosions was already present in this group as early as six months after only one injection.

http://www.rheumatology.org/annual

Editors Notes: Dr. van der Heijde will present this research during the ACR Annual Scientific Meeting at the Boston Convention and Exhibition Center from 2:30 4:00 pm ET on Thursday, November 8, 2007, in Grand Ballroom East. Dr. van der Heijde will be available for media questions and briefing at 8:30 am ET on Saturday, November 10 in the on-site press conference room, Room 251.

Presentation Number: 698

Denosumab Inhibits RANKL, Reducing Progression of the Total Sharp Score and Bone Erosions in Patients With Rheumatoid Arthritis: 12-month X-Ray Results

Dsire van der Heijde1, Stanley Cohen2, John T. Sharp3, Peter Ory3, Lifen Zhou4, Wayne Tsuji4, Richard Newmark4. 1Leiden University Medical Center, Leiden, The Netherlands; 2Metroplex Center for Clinical Research, Dallas, TX; 3University of Washington, Seattle, WA; 4Amgen, Inc., Thousand Oaks, CA

Denosumab is a fully human monoclonal antibody that binds to and inhibits RANKL, a key mediator of osteoclast formation, function, and survival. RANKL-driven osteoclast activity has been implicated in the bone erosions that are characteristic of rheumatoid arthritis (RA).

This ongoing, double-blind, placebo-controlled, phase 2 study was conducted to determine if denosumab treatment could reduce the progression of bone erosions in patients with RA on background methotrexate (MTX).

A total of 227 patients were randomly assigned to receive subcutaneous injections of denosumab 60 mg (n=73) or 180 mg (n=76) or placebo (n= every 6 months. Radiographs of hands and feet were taken at baseline, 6, and 12 months. In exploratory analyses, changes from baseline in the health assessments using the van der Medicine hat news obituary
total Sharp score (TSS) and its components (erosion score and joint space narrowing JSN score) were evaluated at month 6 and month 12. Safety was monitored throughout the study. Increasing scores reflect increased damage.

A total of 202 patients (89%) completed 12 months of study. A smaller increase in mean TSS from baseline was observed in the 60-mg dose group than in the placebo group at month 12 (table; P=.03). The increase in mean TSS was also smaller in the 180-mg group than in the placebo group (table; P=.18). The increase from baseline in the mean erosion score was smaller than placebo for both the denosumab 60-mg and 180-mg groups (table; P

Change in Score at 12 Months
Measurement: Mean (SD) Placebo
N = 71 Denosumab 60 mg
N = 69 Denosumab 180 mg
N = 69
Total Sharp Score 1.87 (5.06) 0.85 (2.52)a 0.97 (2.70)b
Erosion Score 1.34 (4.40) 0.33 (1.22)c 0.19 (1.61)c
Joint Space Narrowing 0.53 (1.49) 0.51 (1.63) 0.78 (1.72)
a P = .03 vs. placebo b P = .18 vs. placebo c P

Denosumab treatment (60 mg and 180 mg) every 6 months reduced progression of TSS and bone erosions compared with placebo, with an adverse event profile similar to placebo.

Disclosure Block: D. van der Heijde, Abbott Laboratories, 5; Amgen, Inc., 5; Pharma
Squibb, 5; Centocor, 5; Chugai, 5; Merck, 5; Schering-Plough, 5; UCB, 5; Wyeth, 5; S. Cohen, Amgen, Inc., 2; Genentech, 2; Biogen Idec, 2; Merck & Co., 2; Sanofi-Aventis, 2; Procter & Gamble, 2; Pfizer, 2; Centocor, 2; Scios, 2; Bristol-Myers Squibb, 2; Wyeth-Ayerst, 2; Amgen, Inc., 5; Sanofi-Aventis, 5; Procter & Gamble, 5; Scios, 5; Wyeth-Ayerst, 5; Genentech, 5; Genentech, 8; Sanofi-Aventis, 8; Procter & Gamble, 8; Amgen, Inc., 8; Scios, 8; Wyeth-Ayerst, 8; J.T. Sharp, Amgen, Inc., 5; Abbott Laboratories, 5; Biogen Idec, 5; P. Ory, Abbott Laboratories, 5; Amgen, Inc., 5; Targeted Genetics, 5; Tanabe, 5; Fujisawa, 5; L. Zhou, Amgen, Inc., 1; Amgen, Inc., 3; W. Tsuji, Amgen, Inc., 1; Amgen, Inc., 3; R. Newmark, Amgen, Inc., 1; Amgen, Inc., 3.

Newswise — Phase III testing shows that a potential new therapy called tocilizumab is safe and effective in the treatment of rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Boston, Mass.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 2.1 million Americans have RA, most of them women.

Researchers tested the effectiveness and safety of tocilizumab, a new humanized, anti-human IL-6 receptor antibody, in patients with moderate to severe active RA despite being treated with methotrexate. Tocilizumab blocks the function of interleukin-6, a molecule that plays a fundamental role in maintaining the inflammation that affects patients with RA.

623 medicine news in this double-blind, placebo-controlled, phase three trial were randomly given 8 mg/kg of tocilizumab, 4 mg/kg of tocilizumab, or placebo intravenously every four weeks for twenty-four weeks. All participants received weekly doses of methotrexate throughout the study. No other disease-modifying anti-rheumatic drugs, or DMARDS, were allowed.

Researchers found that a significantly higher proportion of patients treated with tocilizumab showed improvements in the primary endpoint (ACR 20 at 24 weeks). The ACR 20 response was achieved by 59 and 48 percent of patients receiving tocilizumab at 8 and 4mg/kg, respectively, compared to 27 percent on placebo. The more stringent ACR 70 response was achieved by 22 percent of patients treated with 8mg/kg tocilizumab, but only two percent of patients receiving placebo.

The ACR 20/50/70 scoring criteria measures improvement in tender and swollen joint count and improvement in at least three of the following five criteria: pain; level of disability; overall self-assessment; overall physician assessment; and level of acute phase reactants (including the C-reactive protein or sedimentation rate).

Adverse events were similar across all groups of participants. Of 41 serious adverse events affecting approximately six percent of participants in each group, 15 were considered related to the study treatment and 11 led to discontinuation of treatment. Serious infections were observed more often in the participants treated with tocilizumab than the placebo group (2.9 percent in the 8 mg/kg group, 1.4 percent in the 4 mg/kg group, and 1 percent in the placebo group).

The data prove that IL-6 is importantly involved in the inflammatory response of RA, and that targeting the IL-6 receptor with tocilizumab is a useful novel treatment modality, said Josef Smolen, MD; professor of medicine; chairman, department of internal Medicine III and division of rheumatology; Medical University of Vienna; Chairman, 2nd department of medicine, Hietzing Hospital; Vienna, Austria; and an investigator in the study.

The ACR is an organization of and for physicians, health medicine hat news obituary
, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and internal medicine news
diseases. http://www.rheumatology.org/annual

Editors Notes: Andre Beaulieu, MD, will present this research during the ACR Annual Scientific Meeting at the Boston Convention and Exhibition Center from 2:30 4:30 pm ET on Saturday, November 10, 2007, in Grand Ballroom East. Dr. Joseph Smolen will be available for media questions and briefing at 8:30 am ET on Saturday, November 10 in the on-site press conference room, Room 251.

Presentation Number: 2089

Targeted Inhibition of the IL-6 Receptor with Tocilizumab Effectively Reduces Disease Activity in Patients with Rheumatoid Arthritis

Andre D. Beaulieu1, Andrea Rubbert-Roth2, Thasia Woodworth3, Emma Alecock3, Rieke Alten4, Josef Smolen5. 1Laval University, Quebec, QC, Canada; 2Medical Clinic I, University of Cologne, Cologne, Germany; 3Roche Products Ltd, Welwyn, United Kingdom; 4Schlosspark Clinic, University Medicine Berlin, Berlin, Germany; 5Medical University of Vienna and Hietzing Hospital, Vienna, Austria

Purpose: Interleukin (IL)-6 is central to the regulation of chronic inflammation and is implicated in the pathogenesis of rheumatoid arthritis (RA). An emerging therapeutic approach for RA treatment is targeted inhibition of IL-6 signaling. The aim of this study was to test the efficacy and safety of tocilizumab (TCZ), a novel humanized anti-human IL-6 receptor antibody, in patients with moderate to severe active RA despite treatment with methotrexate (MTX).

Methods: 623 patients were evaluated in this randomized, double blind, placebo controlled phase 3 trial. Patients received either 8 mg/kg TCZ, 4 mg/kg TCZ, or placebo intravenously every 4 weeks. All groups received MTX at stable pre-study doses (10-25 mg weekly) throughout the study. No other disease-modifying anti-rheumatic drugs (DMARDs) were allowed.

Results: A significantly higher proportion of TCZ-treated patients showed improvements in the primary endpoint, ACR20 at 24 weeks (TCZ 8 mg/kg 59%; TCZ 4 mg/kg 48%; placebo 27%; p

Conclusions: This large phase 3 study provides evidence that IL-6 plays a fundamental role in maintaining the inflammation that drives RA. Inhibition of the IL-6 receptor and the subsequent signaling cascade with TCZ improves the signs and symptoms of RA significantly, with a good safety and tolerability profile.

Disclosure Block: J. Smolen, Clinical Department of Rheumatology University Clinic for Internal Medicine I, Vienna, Austria, 3; F Hoffmann La Roche, 5.

Newswise — New research in animals suggests why the commonly prescribed pharma
drug ezetimibe (Zetia) is so potent. The research, reported by scientists at Wake Forest University School of Medicine, is reported online today by the Journal of Clinical Investigation and will appear in the July 2 print issue.

It had previously been thought that the drug works by preventing cells in the intestine from absorbing cholesterol. The new research suggests that Zetia also works in the liver. In both locations, the drugs target is a protein known as NPC1L1 that moves cholesterol into the bodys cells. Zetia blocks the proteins actions so cholesterol cannot be absorbed.

Cholesterol comes not only from the foods we eat, but is also produced by the liver. The organ is involved in making cholesterol, as well as in taking up cholesterol and packaging it for the bodys use.

We know that this protein that the drug targets is expressed not only in the intestine, but is abundant in the human liver, said Ryan E. Temel, Ph.D., lead author.

The scientists made the discovery about Zetias dual action by studying mice that were specially engineered to produce NPC1L1 in the liver. When there were high levels of the protein in the liver, which enhanced cholesterol absorption by the cells, there was a drastic reduction in cholesterol levels in the bile. But when the mice were treated with Zetia, the cholesterol levels returned to normal, suggesting that the drug targets NPC1L1 in the liver.

These findings suggest that in humans, the drug may reduce cholesterol levels in the blood by inhibiting NPC1L1 function in both the intestine and liver, said Liqing Yu, M.D., Ph.D., senior researcher and an assistant professor of pathology, Section on Lipid Sciences.

The researchers theorize that when Zetia blocks this process in the liver, the cholesterol that cannot be absorbed is secreted into bile, the digestive juices that are stored in the gallbladder. Normally, most of biliary cholesterol is secreted from the body in the feces. However, when the bile contains too much cholesterol, gallstones can result. These hardened pieces of cholesterol can block the passageway from the gallbladder to the intestine, resulting in severe abdominal pain, liver damage and nutrient malabsorption.

The fact that Zetia works in two locations is positive because it makes it more effective as a cholesterol-lowering drug, said Temel. But our research suggests the potential for having too much cholesterol in the bile, which could possibly cause gallstones.

The researchers hope to study the question in monkeys and said more research is needed to see if the drug increases gallstone formation in some people.

Until more research is done in animal models that naturally express the protein, it is difficult to say whether this would apply to humans, said Yu.

Co-researchers were Weiqing Tang, M.D., Yinyan Ma, B.S., Lawrence Rudel, Ph.D., and Mark Willingham, M.D., all with Wake Forest, Yiannis Ioannou, Ph.D., and Joanna Davies, Ph.D., both from Mount Sinai School of Medicine, and Lisa-Mari Nilsson, M.D., from Karolinska University Hospital Huddinge in Stockholm, Sweden.

About Wake Forest University Baptist Medical Center: Wake Forest Baptist is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the universitys School of Medicine. The system comprises 1,282 acute care, medicine hat news obituary, rehabilitation and long-term care beds and is medicine
ranked as one of Americas Best Hospitals by U.S. News & World Report.