|
Volume I Summer 1999
A Message from the Chairman
By Steven B. Abramson, MD
Viscosupplementation Therapy For Osteoarthritis
Treatment With Hyalgan And Synvisc
By Gary Solomon, MD
Treating Systemic Lupus Erythematosus
By H. Michael Belmont, MD
Volume II Spring 2000
Breakthroughs for the Millenium
By Steven B. Abramson, MD
Medical Management of Chronic Pain
By Harry Shen, MD
Questions and Answers on Fibromyalgia
By Bertha Bauer, MD
About Clinical Research at Hospital for Joint Diseases
By Clifton Bingham III, MD
New Arthritis Drug Hit the Market
By Brian Golden, MD
A message from the ChairmanI am
proud to announce the opening of our new Center for Arthritis and Autoimmunity. We selected this name because it reflects the broad array of services provided by our physicians and staff. The Center for
Arthritis and Autoimmunity is designed to provide you with a well-coordinated, comprehensive program for the prevention, diagnosis, and treatment of musculoskeletal disorders. The uniqueness of the Center rests on
its ability to offer an integrated and interdisciplinary approach to the care of patients with rheumatologic conditions. This includes complete rheumatologic evaluations, orthopaedic and neurological consultative
services, participation in clinical trials using the most advanced interventional therapies, physiotherapy, and highly sophisticated diagnostic tests as well as complementary medicine. As part of the
Center, we have developed a website which will provide information for patients and physicians regarding the latest treatments for arthritis and other autoimmune diseases. There are 40 million people in
the United States who suffer from some form of arthritis or inflammation of their joints. Arthritis is one of the major causes for many lost work days and it can be a serious disability. Arthritis mainly
affects adults, but some children have it too. When the joints of the body, such as the knees or hips, become inflamed this is the body's reaction to an injury or disease. The inflammation causes swelling,
stiffness and pain. One of the more common forms of arthritis that we treat here at HJD is Osteoarthritis. In this disorder, the cartilage covering the end of the bone gradually wears away. Another
form of Arthritis you might hear about is Rheumatoid Arthritis. In this disease, there is swelling within the lining of the joints and chemical substances are released within the patient's body that attack
and destroy the joint surface. These forms of arthritis and others are treated in different ways at HJD. For example, Arthritis is sometimes treated with medications including oral drugs and
injections. In other cases, the use of canes, crutches, etc. is recommended to help relieve stress on arthritic joints, and, when necessary, surgery is also performed. Autoimmune diseases such as lupus affect
the body's ability to differentiate between foreign substances and its own cells. In the human body, it is the immune system that is responsible for warding off disease and for helping to heal a person who has
already contracted a disease. When the immune system recognizes foreign substances inside the body such as viruses or bacteria that can potentially do harm, it sends out antibodies to attach to them and transport
them to other cells responsible for destroying them. In a person affected by lupus, the immune system sometimes confuses the body's own cells with foreign invaders. It mistakenly identifies cells that belong
to the body as harmful and releases antibodies to attack those cells. This type of disease in which the immune system fights against its own body is called an autoimmune disease. Here at HJD we treat many
patients with lupus and other autoimmune diseases. I hope these basic facts will increase your understanding of the disorders we treat in The Center for Arthritis and Autoimmunity. VISCOSUPPLEMENTATION THERAPY FOR OSTEOARTHRITIS
TREATMENT WITH HYALGAN AND SYNVISCA newly developed therapy for the treatment of Osteoarthritis of the knee is injection of a viscous, lubricating material called hyaluronic acid into the joint via
a series of injections. This is an attractive therapy for patients who have advanced Osteoarthritis of the knee(s), are intolerant of available oral medications, and wish an alternative treatment option other than
surgery.
A normal joint consists of the articulation of two bony surfaces, each of which is lined with a smooth surface of cartilage. The joint is surrounded by synovial fluid which coats and lubricates the
joint to further reduce friction between the two bones. One of the major constituents of the synovial fluid is hyaluronic acid which serves the double function of mechanical lubrication and nourishment of the
cartilage. With Osteoarthritis, due to aging or trauma, the cartilage lining the joints becomes pitted and irregular and the synovial fluid becomes less viscous due in large part to a reduction in the
concentration of secreted hyaluronic acid. Viscosupplementation represents an attempt to return the viscosity of the synovial fluid to normal by injection of supplemental hyaluronic acid. There are two
available products for viscosupplementation, Hyalgan and Synvisc. Hyalgan and Synvisc both have proven effective in the short term management of Osteoarthritis of the knee in controlled studies. There are no
studies comparing the efficacy of the two products. Synvisc has a higher molecular weight than Hyalgan and requires 3 weekly injections compared to 5 weekly injections of Hyalgan. The cost of 3 Synvisc
injections is roughly the same as for 5 Hyalgan injections. Each can provide up to six months relief of the injected knee with benefits comparable to non-steroidal anti-inflammatory agents. Neither "cures"
the disease or prevents the need for future knee replacement, but can provide short term alternatives in patients for whom surgery is not desirable at the present time either because of other medical issues, or personal
convenience. While Viscosupplem- entation would likely to be beneficial for other joints such as the hip or ankle, the FDA has not approved its use for joints other than the knee. Both medicare and many
managed care companies will cover the treatments if the need for the treatment is sufficiently documented by the treating physician. The cost of Viscosupplementation is such that it is not recommended
as initial therapy, but rather should be reserved to patients who do not respond to initial treatment with exercise, acetaminophen, non-steroidal anti-inflammatory agents, and intra-articular steroids. Consult
your physician to see if you would be an appropriate candidate for this therapy.
Systemic Lupus ErythematosusSystemic Lupus Erythematosus (SLE), or as it is commonly known, lupus, is an uncommon although not rare
systemic rheumatic disease which is 9 to 10 times more frequent in women than men. Although lupus may occur at any age and in both sexes it is chiefly a disorder of women of child bearing age (70% or 7 out of
every 10 with the disease are women between the age of 15 and 50). lupus is four times more common in African Americans than Caucasians and also affects Asians and Hispanics with an increased prevalence. It is estimated
between one to one and a half million Americans suffer with this condition. SLE is a classic autoimmune disease. The immune system is intended as a defense against invading infection (i.e. viruses,
bacteria, and parasites) but in lupus this system goes awry and results in the formation of molecules such as autoantibodies, immune complexes, and complement which may attack organs of the body. Although lupus is a
chronic, potentially life-long condition it is characterized by episodic activity. In other words, patients unpredictably experience
disease flares followed by periods of disease inactivity.
Additionally, during a flare, lupus may effect the skin, joints, kidney, brain, lung, heart and gastrointestinal tract although it is unlikely that in any patient all these systems would be involved. In
fact, each lupus patient is unique and the severity, frequency, and extent of injury varies form patient to patient. Research at the Hospital for Joint Diseases and New York University School of Medicine
helped in our understanding of disease flare. We recognize that flares result either from increased inflammation of the blood vessels within organs of the body or, in other instances, from the formation of blood clots
within these vessels. Distinguishing between these two types of injuries is important. One is treated with anti-inflammatory medication, such as NSAIDs (nonsteroidal anti-inflammatory drugs), antimalarials
(hydroxychloro-quine/plaquenil), steroids (prednisone, medrol), or in the severest situations chemotherapy (azathioprine/imuran, methotrexate, cyclophosphamide/cytoxan) while the other with medicines intended to prevent
clotting, such as aspirin, ticlid, plavix, heparin, lovenox, or coumadin. Our research also identified combinations of blood tests that helps predict disease flare. We have observed that blood tests for
anti-double stranded DNA levels and a complement test, C3a, available only in research laboratories such as ours, rise in anticipation of lupus flares. Based on these findings, we are currently enrolling
patients in the National Institute of Health funded Serologically Active Clinically Silent (SACS) Trial where we monitor these blood tests and use a short period of treatment with low dose prednisone to prevent major
lupus flares. Approximately half of all SLE sufferers experience kidney inflammation. In 20%, despite appropriate treatment, kidney damage develops and progresses to end stage renal disease (ESRD). ESRD
patients require dialysis, a blood purifying process which substitutes for damaged kidneys. Patients evaluated in the Center for Arthritis and Autoimmunity have access to rheumatologists with special expertise in this
area-the diagnosis and treatment of lupus nephritis. Additionally, the Center provides a nephrologist (kidney specialist), kidney biopsy, and aggressive approaches to difficult cases with drug treatments such as
steroids, intravenous solumedrol, intravenous cyclophosphamide, cyclosporine, or mycophenolate mophetil. We also have available for our patients research drugs which are anticipated to be more effective yet less toxic
than standard treatments otherwise accessible. Patients interested in the SACS study or any of our other research trials (Safety of Estrogen in lupus, LJP394 B cell tolaragen or Anti-CD40ligand for
kidney disease, or DHEA) may call (212) 598-6650
Breakthroughs for the Millenium
By Steven B. Abramson, MD
As we enter the new millennium, the face of medicine and medical research is changing. Articles in this and prior issues of NewsRheum highlight new and future treatments for arthritis and related conditions. When you get beyond the specifics of the exciting new therapies, a large picture emerges. We have in fact entered an unprecedented era of scientific discovery and drug development.
The advances in biological research over the past two decades have revealed an understanding of disease processes cell by cell, molecule by molecule. Computer technology and bioinformatics, which we marvel at in all areas of our lives, have had a huge impact on drug development. Molecular discoveries made in the laboratory can be modeled by computers, providing information that allows medicinal chemists to formulate designer drugs. The time from a discovery of a target molecule in the lab, to the development of a drug and the evaluation of the drug in large clinical trials, can now be achieved in under a decade. So, in this new era we can be faster, more molecular, highly targeted and less toxic. But that is not where it ends. The next decade will see another quantum change via the impact that an understanding of genes that contribute to disease processes and responsiveness to drugs. The Human Genome Project will reveal the secret codes. Scientists will discover which genes cause and protect against specific diseases. Small differences in the genetic code among individuals will be identified that determine whether an individual will respond to one drug or another. This emerging field of pharmaco-genomics will be one more advance by which doctors will be able to provide the most targeted and safest therapy.
We embark on a new, exciting era in Medicine: molecular, translational, technological, genomic. Most importantly, we enter an era that will be characterized by improved treatments for arthritis, treatments carefully designed for the individual patient.
The Medical Management of Chronic Pain
By Harry Shen, MD
The most common complaint of the rheumatology patient is joint pain. Most patients with inflammatory forms of arthritis respond well to conventional anti-rheumatic therapy, i.e., nonsteroidal anti-inflammatory drugs (NSAIDs), intra-articular steroid injections or disease modifying agents such as methotrexate. Patients who have severe inflammatory or degenerative arthritis of the hip or knee may undergo joint replacement surgery. Some patients, however, do not respond adequately to maximum anti-rheumatic therapy and may not be surgical candidates. Patients who are in chronic pain (greater than 6 weeks) often develop a variety of other problems that tend to magnify their pain and impair their ability to function. These include the development of depression, deconditioning (deterioration of physical condition due to limited activity), poor body mechanics and maladaptive behavioral patterns. These patients can be considered candidates for a pain management program.
The Pain Program at Hospital for Joint Diseases utilizes a multidisciplinary approach. Patients are given a full evaluation, and their diagnosis as well as prior therapy is re-examined. An alteration of their medications is often recommended. Some examples of this:
- An older individual with severe degenerative arthritis of the knee who has had several heart-attacks and thus is not eligible for surgery. Many of patients such as this one receive NSAIDs but fail to obtain adequate pain relief. An opiod analgesic may well lessen such a patient's suffering.
tiple sources for pain. A portion of the
pain may originate from nerve compression and other pains may
originate from facet arthritis. Opiods and NSAIDs may well help
the "mechanical" pain, however any radicular or neuropathic pain
may well respond better to other medications such as one of the
tricyclic antidepressants or one of the epilepsy drugs such as
Gabapentin.
- A patient with a "failed" low back, i.e.
prior multiple surgeries for herniated discs. Such patients often
have mul
Physical therapy is a key component in the rehabilitation of the patient with chronic musculoskeletal pain. A gradual and gentle exercise program often works well in this population. A variety of approaches such as modified yoga based exercises, Feldenkrais, or Tai-Chi have all been used with success. Occupational therapists can teach proper body mechanics, energy conservation measures, joint conservation measures, and other approaches to maximize function despite the patient's pain and anatomical abnormalities. Instruction by a psychologist in biofeedback techniques, stress management techniques, and relaxation techniques, can help patients learn how to manage their pain. Another method for managing pain includes nerve block procedures, which are also available at the Pain Center. When appropriate, a psychiatrist addresses depression and other emotional issues, and family issues are often addressed by the social worker. Patients with lesser degrees of impairment can be treated as an outpatient however the most severe case are probably best served in the context of a structured inpatient program.
Questions and Answers on Fibromyalgia
By Bertha Bauer, MD
Q: What is Fibromyalgia?
A: Fibromyalgia is a painful, chronic illness that affects the muscles and the soft tissue especially in specific areas of the body known as trigger points. Some Patients feel constantly fatigued and ache all over. Fibromyalgia is believed to be a neurotransmitter dysfunction. Neurotransmitters are chemical agents in the body which control pain, mood, sleep, and the immune system. Some common neurotransmitters are serotonin, melatonin, and dopamine, among others. A person with Fibromyalgia produces abnormal amounts of neurotransmitters, causing havoc in the form of pain, depression, sleep disorders, headaches, and flu-like symptoms. Patients with arthritis show evidence of inflammation or joint abnormalities. This is not the case with Fibromyalgia patients. When tested, many Fibromyalgia patients show no diagnostic lab or x-ray abnormalities,
Q: How, then, does one diagnose Fibromyalgia?
A: A physician can confirm a diagnosis of Fibromyalgia if a patient aches all over and experiences pain when 4 kilograms of pressure are applied to 11 out of 18 specific tender (or trigger) points in the body.
Some common complaints of Fibromyalgia patients include muscle weakness, irritable bowel syndrome, migraines, and sensations of abnormal body heat and cold. It is also common to find Raynaud's disease among patients who suffer front Fibromyalgia. Raynaud's disease is a painful vascular disorder which causes discoloration especially in the fingers and toes upon exposure to cold.
Many patients with Fibromyalgia are often unable to enjoy the normal rejuvenating benefits of deep sleep or delta sleep. There are two levels of sleep: Level I (alpha stage) is the lightest sleep we get. The second stage, or deep sleep, is the most refreshing period of sleep where the body naturally restores itself, producing growth hormones as needed. The deep sleep stage in Fibromyalgia patients is often interrupted. This is a major disadvantage because the body cannot heal itself.
Fibromyalgia is difficult to diagnose because many of its symptoms overlap with other illnesses, such as chronic fatigue syndrome. It is also a difficult condition for the family and friends of patients to comprehend because the Fibromyalgia patient often doesn't look sick.
Q: What is the prognosis for people with Fibromyalgia and how can the symptoms be controlled?
A: While painful and extremely disruptive to any lifestyle, Fibromyalgia is not a progressive or crippling disease. Though there is no known cure and it is difficult to treat, patients can expect some improvement if they follow several control measures under the guidance of a rheumatologist experienced in treating Fibromyalgia.
- Keep regular sleep hours and get enough sleep.
- Take appropriate medication to improve deep sleep.
- Perform daily gentle aerobic exercise.
- Avoid undue physical and emotional stress.
- Undergo treatment for any coexisting autoimmune or arthritic condition.
- Seek behavioral therapy, if appropriate.
- Keep Informed of developments in Fibrormyalgia treatments,
If you suspect you may have Fibromyalgia, seek out physician who specializes in Fibromyalgia for the best results. Rheumatologists, or physicians with a special interest in pain management, may be helpful.
About Clinical Research at Hospital for Joint Diseases
By Clifton Bingham III, MD
The Ambulatory Clinical Research Center at the Hospital for Joint Diseases was established to coordinate the efforts of our physicians conducting patient-oriented research. One type of clinical research is called a Clinical Trial and involves testing new medications for arthritis, autoimmunity, bone diseases, and pain. Clinical studies also look at ways to prevent, detect, diagnose, control, and treat different types of diseases. Another type of clinical research involves following a group of patients with a particular condition to determine what factors may be important in predicting flares or worsening of disease before a person feels sick, as well as to recognize indicators of improvement and good prognosis. Clinical research studies are also conducted to better understand how an illness affects a patient in terms of the psychological and economic impact, and importantly to evaluate the level of disability that results from an illness.
Exciting new developments in Cell and Molecular Biology and Genetics are allowing us to understand some of the underlying causes and mechanisms of Arthritis and Autoimmune diseases. These developments in the laboratory in turn are permitting physicians to diagnose conditions earlier and with greater accuracy and to offer treatment at earlier stages in order to prevent or slow progression of a disease and its attendant disability. Pioneering work was conducted at the Hospital for Joint Diseases that led to our understanding that certain genetic markers defined a subset of patients with rheumatoid arthritis that may have more severe disease. Likewise, seminal observations involving systemic lupus erythematosus (SLE), antibodies in this condition, and lupus pregnancy have been conducted by our researchers. Our researchers continue to bridge the gap between the "bench and bedside" in studies that integrate basic science investigations with clinical observations and outcomes through studies that involve analysis of blood, joint fluid, and genetic markers that may help to predict responses to therapy.
The advances in our understanding of disease mechanisms also have allowed therapies that target specific mediators and pathways that are involved in a particular condition. One recent example are the new anti-inflammatory medications, the COX-2 inhibitors celecoxib (Celebrex) and refecoxib (Vioxx) that are designed to be specific for a particular protein that causes pain and swelling but that have little effect on the stomach lining. Other examples are the powerful new therapies for rheumatoid arthritis, etanercept (Enbrel) and infliximab (Remicade) that interfere with a particular protein that leads to joint destruction and inflammation in this condition.
A clinical trial is established in order to test the effectiveness of new medication, a new way of administering an established medication, or a new medical procedure. In clinical trials, the new treatment or procedure is compared with an existing treatment or with a placebo (a sugar pill) to see if the new treatment is more effective or safer than the existing therapy. A clinical trial is intended to find better ways of treating patients with a disease. At the Hospital for Joint Diseases, we conduct clinical trials for patients with different types of arthritis, such as rheumatoid arthritis and osteoarthritis, other inflammatory and autoimmune conditions such as lupus, as well as for osteoporosis, metabolic bone diseases such as Paget's disease and hyperparathyroidism, and studies of new medications and treatments for pain.
A new product must be proven to be effective and have an acceptable side-effect profile before it is brought onto the market. This information is gained through clinical trials. All new treatments that are developed must go through this type of careful investigation. All existing treatments have gone through the same type of testing. Often times new medications are modifications of existing medications that are designed to be safer or more effective. Before a new treatment is tested in patients, extensive laboratory evaluation is performed. First the effects of a drug are studied in the test tube or in cultured cells, then the drug is administered to animals to evaluate its effectiveness, safety, and side effects. This information is then presented to the Food and Drug Administration (FDA) by the pharmaceutical company. The FDA then grants the company permission to conduct further studies in people in a clinical trial. The clinical trial is designed to provide information on the effectiveness and risks of a new treatment.
Our physicians / researchers conduct investigations for new therapies and drugs in the treatment of autoimmune diseases, rheumatoid arthritis and osteoarthritis, osteoporosis and metabolic bone diseases. Many of our patients have benefited from new therapeutic agents several years before these products were available to the general public, for example the selective COX-2 inhibitors, medications for osteoporosis, biologic therapy for rheumatoid arthritis, and injections for osteoarthritis. In a trial of an new therapy, the study medication is usually given free of charge, and blood tests, X Rays, physical exams, bone density measurements, and other diagnostic testing may also be provided as part of a particular study. At the conclusion of a clinical trial, patients often find that they are more aware of how their condition affects them because they are asked to monitor symptoms that may have previously been overlooked. This in turn helps them to become more active participants in their medical care.
At the Center for Arthritis and Autoimmunity, Rheumatologists and other physicians are aware of the ongoing studies throughout the hospital, and can notify you of your eligibility if a study may benefit you. We display listings of ongoing studies in our offices, as well as on our hospital web site, and in publications such as this one.
This is an exciting time for the therapy of Arthritis, Autoimmune Diseases, and Osteoporosis, with current medications that target specific parts of the disease process, and with fewer side effects. The future holds many equally exciting prospects for treatment. We welcome your questions. If you would be interested in further information, please contact us at 212-598-6613 or at hjd.acrc@med.nyu.edu.
Current Studies
Rheumatoid Arthritis:
- 1 month study for new oral medication for pain
- Addition of a medication to block the effects of an inflammatory
protein (interleukin-1).
Systemic Lupus Erythematosus:
- Study to follow laboratory parameters as related to disease activity and effects of early treatment in patients with abnormal laboratories.
- Study for patients with Lupus Nephritis with CellCept (Mycophenalate Mofetil.)
Osteoarthritis:
- Use of an oral medication to slow progression of arthritis and joint space narrowing.
Osteoporosis:
- Study to re-evaluate Alendronate (Fosamax) in patients who have previously had stomach upset with this product.
Hyperparathyroidism:
- Oral medication to treat elevated calcium associated with this Disease.
New Arthritis Drug Hit the Market
By Brian Golden, MD
As any patient with arthritis knows, arthritic joints can be painful, stiff, and often swollen. For decades, the mainstay of medical treatment for arthritis has been the so-called Non-Steroidal Anti-Inflammatory Drugs, or NSAIDs. This class of drugs includes such agents as aspirin, ibuprofen (Motrin, Advil), Naproxen (Naprosyn, Aleve, Anaprox), and many others. NSAIDs have been clinically helpful for arthritis sufferers in that they relieve the pain and inflammation of involved joints and help to restore more normal daily function for patients. It was proposed almost 30 years ago that the NSAIDs work in the body by blocking the formation of certain products called prostaglandins, made in diseased tissues such as arthritic joints. Prostaglandins, however, are also made under normal circumstances in certain healthy tissues such as the stomach and kidneys. The prostaglandins of disease are made by an enzyme in the body called COX-2, while the normal healthy tissues make prostaglandins via an enzyme called COX-1. Traditional NSAIDs block both these COX-2 -derived "bad" prostaglandins in the arthritic joints (the effect we want) and the COX-1- derived "good" prostaglandins in the stomach (causing the unwanted side-effects such as stomach pain, stomach ulcers, and possibly bleeding from these ulcers).
The new drugs just entering the market are called Selective COX-2 Inhibitors. Celecoxib (Celebrex) is being marketed jointly by Searle and Pfizer, while Rofecoxib (Vioxx) is made by Merck. As the name "selective" implies, these agents have been shown to block the "bad" prostaglandins made by COX-2 in diseased, inflamed, arthritic joints, while not blocking the normal prostaglandins made by COX-1 in healthy stomach and kidney. Clinical trials of these medications in patients have shown that they are, in fact, effective in the treatment of pain and various types of arthritis, including osteoarthritis and rheumatoid arthritis, without increased risk of ulcers or kidney problems characteristic of conventional NSAIDs.
Are these new selective COX-2 blockers, however, the "super-aspirins" touted in the media? The answer is: not exactly. Ultimately, the new COX-2 inhibitors will probably prove to be equally effective in terms of pain relief and anti-inflammatory strength, while having a superior safety profile, to traditional NSAIDs. There is no doubt that they represent a significant advance for the millions with arthritis, but a true "cure" they are not. Both doctor and patient should exercise cautious optimism at this exciting juncture.
|
|
