With this first volume of the UPMC Arthritis Newsletter, we begin a series of publications designed to inform our patients about arthritis and musculoskeletal diseases. We intend to publish a volume of this newsletter every 3 months. We will emphasize new medications and treatment approaches which are now available or currently being tested, including opportunities that you will have to participate in, and benefit from, such research.

Periodically, we will include an "Ask the Doctor" column to give patients the opportunity to ask questions of particular concern to them. Also, we will profile Network physicians and update you on their important research activities and accomplishments. Programs available to enhance our knowledge of arthritis and improve patient care will be highlighted.

The various forms of arthritis can be disabling and often force patients to change their activities, life style, and aspirations for the future. In these and other chronic, life-long diseases, patients must be active participants in their care in order to achieve the best results. We believe that educated, informed arthritis patients are better able to work with their rheumatologists to maximize their health and productivity.

We look forward to working with you. We hope that the Newsletter will provide an informative method of communication.

The physicians and staff of these affiliated practices work closely together in the Arthritis Network to develop and implement programs for up-to-date evaluation and management of arthritis patients. In addition, they coordinate research studies of new medications which offer patients access to the latest treatments. Their close interactions have resulted in the recent opening of 6 new offices which now serve patient populations of need in our geographical area.

The current practice locations and affiliated hospitals served by the UPMC Arthritis Network are:

The UPMC Arthritis Network Registry is a project of the Network physicians designed to maximize our ability to do arthritis treatment research and to inform interested patients about opportunities to participate in such research. The Registry is generously funded by the St. Margaret Memorial Hospital Foundation.

The Registry is a computer listing of patients with their Network rheumatologist's diagnosis, for example osteoarthritis, rheumatoid arthritis, or osteoporosis, along with their age, address and telephone number. You may receive a letter from your Network physician asking if you are interested in participating in the Registry.

Here is a hypothetical example. Let's say that the Network has been contacted by a pharmaceutical company about participating, along with other medical centers, in testing a new product. The company has developed a cream which if applied to a knee with rheumatoid arthritis twice daily, may reduce pain and increase mobility. The Network Research Committee reviews the information and finds it an attractive and interesting project. The cream will be tested for 4 weeks in persons with rheumatoid arthritis, age 35-74. The Pittsburgh Center's quota is 15 patients. Some patients will receive the cream and others a placebo.

Twenty-five dollars will be given to all patients who finish the study, which requires a total of 3 visits to the study center, 2 blood samples and completion of 4 questionnaires. At the end of the study, all participants are given a 3-month free supply of the cream.

If you are a Registry patient in the correct age group who has rheumatoid arthritis, we would be able to identify you immediately by computer. You would then be contacted and given the opportunity to participate in this study, if you had one or both knees affected, before any general advertising was done.

There is no obligation to participate in any of the Network research studies. You may remain a member of the Registry and receive study announcements even if you have decided not to participate in a study in the past.

Over the next several years, the Registry will grow to include many rheumatic diseases, beginning with rheumatoid arthritis. If you have rheumatoid arthritis, you will receive a letter of invitation from your rheumatologist within the next several months. The letter will contain information about the Registry and a "consent form". In order to participate in the Registry, a patient must simply sign and return the form, as directed. Signing the consent means only that you are willing to receive information about research projects in which you might be eligible to participate.

The Registry is supervised by the members of the Network Research Committee, which has representatives of the three large Network practice groups. The Registry Coordinator is Jennifer Jablon, who can be reached at (412) 383-8674.

In the past 6 months, three new drugs have been approved by the Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis (RA). All will be relatively expensive compared with the currently prescribed drugs.

The first is Arava, an oral medication which closely resembles methotrexate in its mechanism of action and ability to control joint inflammation. Methotrexate and Arava are considered disease-modifying anti-rheumatic drugs (DMARDs) which means that they are capable of modifying the course of RA so that less joint damage and deformity will result. If there is to be a benefit from Arava, it usually occurs within the first 2-3 months after the drug has been started. These drugs, like virtually all others, have potential side effects. Both may cause nausea and liver abnormalities thus requiring blood test monitoring, but Arava, unlike methotrexate, has not been found to injure the lungs. Arava causes serious fetal abnormalities, and women of childbearing age must use effective birth control and take special precautions if planning a pregnancy.

Enbrel is the first of a new class of DMARD drugs called "biologic modifiers", so named because these products are specifically designed to block the effects of important proteins called cytokines which trigger rheumatoid joint inflammation. Enbrel blocks the action of tumor necrosis factor (TNF), a "bad actor" in RA joints. It is given as a self-administered injection just below the skin twice a week. Results thus far indicate that it

is equal to methotrexate in controlling the symptoms of RA, yet has minimal side effects. The most common problem, seen in roughly 25% of patients is a mild rash at the injection site. While benefits from this drug appear dramatic in many patients, some concerns remain that this powerful treatment may increase the risk of infection and cancer.

Osteoarthritis (OA) is the most common form of arthritis and affects more than 17,000,000 Americans and over 250,000 persons in our southwestern PA geographical area. The knee is one of the most frequent targets of OA, resulting in pain, disability and substantial health care expenditures.

A group of investigators led by Terence W. Starz, M.D. have developed a method of evaluating three key aspects of knee OA - pain, function and structure (PFS) in order to better classify patients into subgroups which assists in predicting disease progression and in designing more specific treatment. They have studied over 200 patients from primary care, rheumatology and orthopaedic surgery practice sites. These researchers have presented a number of papers at national arthritis meetings which have highlighted their methods of determining a PFS score for each knee affected by OA and using this information to recommend various treatment programs which include patient education, exercises, training in improving the ability to accomplish activities of daily living, weight control, medications and guidelines for referral to a specialist.

Patients interested in learning more about the Knee OA Program may contact Donna Levitt at (412) 647-3255.

Osteoarthritis, the most common form of arthritis, occurs in joints when the cartilage that covers the ends of bones deteriorates. Pain and stiffness often occur as a result.

Arthritis investigators at the University of Pittsburgh and five other research centers are studying the drug Doxycycline, a commonly used antibiotic, as a possible treatment for osteoarthritis. Scientists have found that doxycycline blocks the action of a protein responsible for breaking down collagen, an important component of the framework of cartilage. They will study whether doxycycline can slow the breakdown of collagen and thus reduce progression of osteoarthritis of the knee or even prevent its development. Women between the ages of 45 and 54 who are above average weight and have osteoarthritis in one knee are eligible for participation. Approximately 72 women will be followed for a thirty-month period. One half of the women will receive doxycycline 100mg twice a day and half will receive a placebo (sugar pill). This study is being funded by the National Institutes of Health. Drs. Chester V. Oddis and Susan Manzi are directing the University of Pittsburgh's Study Center.

For additional information call the Women's Arthritic Knee Study at 624-9626 or 1-800-872-3653.

Many autoimmune diseases affect women more than men, suggesting that sex hormones play a role in development of these diseases. There is evidence that sex hormones influence the immune response. Estrogens have been shown to increase immunity while male hormones can dampen the immune system. Systemic lupus erythematosus (SLE) is the best example of an autoimmune disease which affects women significantly more frequently than men. The peak onset of SLE occurs between the ages of 15 and 45 (the childbearing years) when 10 times more females than males acquire the disease.

Much of the evidence to suggest a role for sex hormones in the development of lupus has been learned from certain strains of mice which develop SLE. Onset of lupus in some of these mice is earlier and the disease more severe in females than in males. In addition, treatment of females with androgen (male hormones) postpones death.

There is also evidence in humans with SLE that hormones may be important. Both male and female SLE patients have been found to have abnormalities in estrogen metabolism; they have elevated levels of a more potent estrogen byproduct and lower blood levels of testosterone (male hormone) than predicted.

replacement therapy are sometimes avoided in lupus patients despite the clear benefit of these medications in providing effective birth control and preventing cardiovascular (heart) disease and osteoporosis (bone thinning), both of which occur prematurely in patients with SLE.

Susan Manzi, M.D., a Network physician and researcher, is currently involved in 2 studies designed to better understand the role of hormones in SLE. Through an NIH-sponsored grant she will determine whether women with SLE have significantly different sex hormone levels during the menstrual cycle than women without lupus, and whether a relationship exists between a given hormone and disease activity. Estradiol and progesterone levels will be measured from daily saliva specimens throughout three menstrual cycles in 100 SLE women and 100 age-similar women without SLE. Genes which may be important in alterations in estrogen metabolism will be examined. Dr. Manzi is also involved in a project on the safety of estrogen when it is used as an oral contraceptives or for hormone replacement in lupus, a study also funded by the NIH. This study is being performed in many medical centers and will enroll over 1000 women with SLE.

Since women with lupus now live longer due to improved therapy, premature cardiovascular (heart) disease and osteoporosis (bone thinning) have emerged as significant threats to the health of these women. If estrogen is safe for women with lupus, it could be used to prevent these late complications. Dr. Manzi's studies will hopefully clarify the relationship between sex hormones and disease activity in women with SLE.

Thomas A. Medsger, Jr., M.D., Gerald P. Rodnan Professor of Medicine in the School of Medicine, was recently presented with the American College of Rheumatology (ACR) 1998 Distinguished Rheumatologist Award. Dr. Medsger, a member of the faculty in the School of Medicine for more than 27 years, was nominated by faculty colleagues at the University of Pittsburgh Medical Center.

Dr. Medsger is widely recognized for his research contributions, mainly concerning systemic sclerosis (scleroderma) and closely related connective tissue diseases. He has won a Golden Apple award and several other distinction citations for teaching excellence. He has assisted both national and local patient support groups in leadership positions and has been named one of the "Best Doctors in America" by his peers for the past six years.

Timothy M. Wright, M.D., has recently been named the Margaret Jane Miller Professor of Medicine. Dr. Wright is an Associate Professor of Medicine and Chief, Division of Rheumatology & Clinical Immunology at the University of Pittsburgh School of Medicine. He is also Director of the University of Pittsburgh Arthritis Network (see first article). The Professorship is the result of a generous gift to the University by Mr. Russell P. Miller in memory of his wife, who suffered from rheumatoid arthritis.

Dr. Wright, an outstanding scientific investigator, joined the faculty at the University of Pittsburgh School of Medicine in 1991. His primary area of research interest is abnormalities of the immune system in systemic sclerosis (scleroderma). The Professorship will exist in perpetuity and will make an important contribution to the Division's efforts toward finding new treatments and eventual cures for scleroderma, rheumatoid arthritis and many other forms of arthritis.

During the past year, four physicians have joined the Network.

Kenneth Gold, M.D. is a new member of Arthritis & Internal Medicine Associates and Clinical Assistant Professor of Medicine at the University of Pittsburgh School of Medicine. He was an undergraduate at the University of Rochester before completing medical school at Albert Einstein College of Medicine. Dr. Gold was a resident at Jewish Hospital in St. Louis and a rheumatology fellow at the Mayo Clinic. Before coming to Pittsburgh in July, 1998, he was a full-time rheumatologist at the Guthrie Clinic in Sayre, PA for 4 years.

Phillip Klahr, M.D. is also a recent addition to Arthritis & Internal Medicine Associates and has been appointed as Clinical Assistant Professor of Medicine at the University of Pittsburgh School of Medicine. Dr. Klahr is a graduate of Brooklyn College and Albert Einstein College of Medicine. In addition to his M.D. he also received a master's degree in Neuroscience at Einstein. Dr. Klahr was an internal medicine resident at the University of Connecticut before taking fellowship training in both rheumatology at Stony Brook, NY, and allergy/immunology at Washington University in St. Louis. Before coming to Pittsburgh, Dr. Klahr practiced internal medicine and rheumatology and allergy/ immunology in St. Louis.

Dana Ascherman, M.D. joined the University Division of Rheumatology & Clinical Immunology as Assistant Professor of Medicine on the full-time faculty member of the School of Medicine in September, 1998. He completed his undergraduate studies at Harvard University and graduated from Stanford University School of Medicine. Dr. Ascherman finished his internal medicine and rheumatology training at Georgetown University in Washington, D.C. He will devote his time to a combination of arthritis patient care, teaching and research.

William Ridgway, M.D. also became a full-time faculty member and Assistant Professor of Medicine in the Division of Rheumatology & Clinical Immunology in September, 1998. He graduated from Haverford College and the University of Rochester School of Medicine and completed both internal medicine and rheumatology fellowship training at Stanford University. After fellowship, he spent 4 years as a post-doctoral research fellow and research associate in the laboratory of Dr. C. Garrison Fathman, a well-known immunologist. Dr. Ridgway's laboratory at the University of Pittsburgh will focus attention on increasing our understanding of genes and other factors which influence the immune response in rheumatic diseases. He also serves as the Chief of the Arthritis Clinic at the Oakland Veterans Administration Medical Center.