Remember Dolly? She is the world's first cloned sheep and she was diagnosed with arthritis. There is fear amongst researchers that the cloning process may have given her a genetic defect. Sheep get arthritis but Dolly developed it at an unusually young age. This raises the question, has the incidence of arthritis changed; or is it still a disease mainly associated with aging?
There are more than 100 types of arthritis, but the most common arthritic diagnoses are osteoarthritis, also known as degenerative joint disease, and rheumatoid arthritis (RA). Health experts reported that osteoarthritis of the knees afflicts approximately 10 million people, making it the most common type of arthritis in the United States affecting older people, mostly over 45 years or age. Arthritis affects more than 42 million American adults and children. By the year 2020, the Centers for Disease Control (CDC) estimates that 60 million people will be affected, and more than 12 million will be disabled5.
Treatment of osteoarthritis and rheumatoid arthritis requires a long-term approach to managing pain, maintaining joint function and slowing or stopping joint damage. Short-term is aimed at reducing joint inflammation. Pain andswelling subside once joint inflammation is reduced. When there is joint inflammation the joint is exposed to further damage.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used medications used to treat arthritis of which acetylsalicylic acid (aspirin) is the most common. The Bayer Company in Germany developed aspirin in the late 1800s but it wasn't until the late 1970s and early 1980s that inflammation and the way aspirin works to control it was understood. 2 Later, other forms of NSAIDs were developed, ranging from over-the-counter Advil, Motrin IB, and Aleve to other medications requiring a prescription.
Since September 1998, new drug treatment strategies have become available to combat the joint inflammation and pain that occurs in osteoarthritis and rheumatoid arthritis (RA). In 1982, Sir John Vane was one of three recipients of the Noble Prize for Medicine for the discovery of how prostaglandins work. 2 Prostaglandins are natural hormones that affect practically every system in the body. Vane discovered that aspirin slows the body's production of some prostaglandins and proposed that aspirin works as a painkiller.2 That idea is not only widely accepted but it also laid the foundation for newer drug discoveries for treating arthritis such as Celebrex and Vioxx.
There are nine new drugs for the treatment of arthritis. They are listed below by category. The brand names are in parenthesis. Each will be presented in detail in this course, including the United States Pharmacopeia (USP) authoritative information about the appropriate use and the FDA alerts & warnings as of 01/04/2003.
Prostaglandins belong to a lipid class of biochemicals known as the eicosanoids. Prostaglandins act similarly to hormones by stimulating target cells into action. They perform a variety of physiological processes. It was originally named “prostaglandins” because the first prostaglandin was found in semen and thought to originate from the prostate gland. However, most of the prostaglandins have nothing to do with the prostate.
Prostaglandins differ from hormones in that they function locally, near their site of synthesis, and they are metabolized very rapidly. Also unusual, is that some prostaglandins act differently in different tissues. Specific prostaglandins appear to have contrary functions; some prostaglandins aggravate inflammatory conditions and some alleviate them. The cyclical prostaglandin compounds are potent, short-lived mediators of the inflammation response. They are not stored in cells but are synthesized as needed in response to injury or irritation. In summary, prostaglandins perform the following functions:
Aspirin and NSAIDs work by inhibiting the enzyme called cyclo-oxygenase (Cox). Blocking Cox reduces the amount of inflammation supporters, prostaglandins, which helps reduce inflammation. Unfortunately, prostaglandins also perform functions that your body requires. Reducing prostaglandins can lead to stomach bleeding and ulcers. Researchers have learned that there is more than one kind of Cox. By blocking only one type of Cox, Cox-2, it may be possible to lower the amount of prostaglandins that promote inflammation, while leaving other types of prostaglandins alone. The newer COX-2 inhibitors, such as Celebrex, Vioxx and Bextra, are thought to be safer anti-inflammatory agents for patients at high risk of ulcer disease or who have had ulcers in the past; however, current research is casting doubt. Individuals who avoid aspirin or other NSAIDs because of allergic reactions or asthma should not take cox-2 inhibitors. In addition, Cox-2 inhibitors can harm the kidneys in people with decreased kidney function.
RA is characterized by chronic synovial inflammation and infiltration of immune and inflammatory cells into the joint. Enlarged synovial tissue, called pannus, can cause the destruction of the adjacent articular structures of the joint, including the resorption of cartilage and bone tissues, and damage to ligaments and tendons. Destructive enzymes associated with cartilage and bone erosion are present at the onset of RA, creating a potential for joint damage very early in the disease. In fact, 70% of RA patients have shown erosion on x-rays within 2 years of the onset of symptoms.
1. It is indicated for the treatment of the signs and symptoms of osteoarthritis and adult rheumatoid arthritis.
2. Mobic 18 (meloxicam) was FDA-approved on April 14, 2000. It is a COX-2 inhibitor marketed by Boehringer Ingelheim Pharmaceuticals5.
3. Vioxx 10, 15, 18: Vioxx (rofecoxib) was FDA-approved on May 21, 1999. It is a COX-2 inhibitor manufactured by Merck in competition to Pharmacia's Celebrex.
4. Celebrex 7,8,18: (celecoxib) was FDA-approved on December 31, 1998. It was first drug approved in the new class known as COX-2 inhibitors marketed by Pharmacia.
The USP Practitioners' Reporting NetworkSM has received, and continues to receive, numerous reports of confusion resulting from the similar names Cerebyx®, Celebrex®, and Celexa®. In addition, USP received one report expressing concern that the nonprescription dietary supplement, CerebraTM could potentially be confused with the prescription products. Table One helps to distinguish among the prescription agents Cerebyx, Celebrex, and Celexa.19
Route(s) of Administration
100 mg PE in 2-mL vials
500 mg PE in 10-mL vials
Fosphenytoin sodium injection
Intravenous or Intramuscular
Source: USP PRNTM
Note: The USP PRNTM requests practitioners continue to report concerns about these look-alike sound-alike names; continued reporting provides data to be compiled that may encourage regulators or manufacturers to take proactive steps that may prevent errors.
Tumor Necrosis Factor (TNF) is an immune system protein that is overproduced in people with rheumatoid arthritis and other inflammatory diseases. It is found in synovial cells and macrophages in the tissues and shares many properties with another cytokine, interleukin-1. Anti-TNF drugs work by blocking this protein. Humira, Enbrel and Remicade are TNF blocking drugs and have similar side effects, including serious and sometimes fatal infections linked to the suppression of the immune protein.
1. It is indicated for RA.
2. Kineret13 (generic name: anakinra) was FDA-approved on November 14, 2001 and is marketed by Amgen.
3. Remicade17, 18: (generic name: infliximab) an anti-TNF was FDA-approved on November 10, 1999, marketed by Centocor.
4. Enbrel 9,18: (generic name: etanercept) was FDA-approved on November 2, 1998 as the first drug in a new class of tumor necrosis factor (TNF) drugs for the treatment of rheumatoid arthritis. Enbrel is manufactured by the Immunex Corporation and marketed by Amgen and Wyeth Pharmaceuticals
In December 2002 Amgen and Wyeth Pharmaceuticals announced that the FDA approved Amgen's Rhode Island a manufacturing facility for Enbrel. With this approval, significant supply of Enbrel is available for patients; in the past Enbrel was often in short supply.
Enbrel users have access to free support tools that make learning the self-injection process easy for patients. Example of available tools are a dosing system kit which includes a step-by-step guide for preparing and injecting Enbrel, a video demonstration of the preparation and injection processes and a “mixing station” which is a specially designed, arthritis-friendly device that makes preparing the Enbrel solution easier. In addition, users have access to a nurse able to answer patient questions about self-injecting. The telephone number is toll-free at 1-888-4ENBREL (1-888-436-2735), Monday through Friday, 9 a.m. to 9 p.m., Eastern Time.
1. Arava was the first oral treatment for active rheumatoid arthritis approved for relieving painful, swollen joints and slowing joint damage.
Even with the newer medications on the market, pharmacological treatment and management of arthritis is best achieved when other modalities are used simultaneously. New medications can be more expensive than previously available therapies. Patients need to be familiar with the risks, benefits, costs and alternatives; hopefully before making a decision with his or her physician. The FDA requires that studies be conducted to establish the safety and effectiveness of any new drug or treatment before it is approved for prescription use. Unfortunately, even thorough studies conducted over several years may not reveal side effects that occur only rarely, or those that occur only with long-term use. In many drug approval processes, healthy individuals are used in studies, which later present as adverse reactions in patients with co-morbidities. Furthermore, most drugs have not been approved for women who are pregnant. Although the risk is usually small, a new treatment might cause a side effect that could not be anticipated by the prescribing physician.
Two good resources for accessing current drug warnings or alerts are the FDA and USP Practitioners’ Reporting Network. Clinicians need to keep current on available drug therapies and FDA alerts in order to better educate the patient, reduce medication errors, and promote the intent of treatment, a better quality of life.
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