Rheumatoid arthritis is a chronic inflammatory disease that leads
to pain, stiffness, swelling and limitation in the motion and function
of multiple joints. If left untreated, rheumatoid arthritis can produce
serious destruction of joints that frequently leads to permanent disability.
Though the joints are the principal body part affected by rheumatoid
arthritis, inflammation can develop in other organs as well.
Over twenty million people suffer from rheumatoid arthritis worldwide
creating a global pharmaceutical market estimated at over $6.3 billion
in 2004. The disease currently affects over two million Americans,
almost 1% of the population, and is two to three times more prevalent
in women. Onset can occur at any point in life but is most frequent
in the fourth and fifth decades of life, with most patients developing
the disease between the ages of 35 and 50.
The main symptom of rheumatoid arthritis is the persistent inflammation
of the joints, usually in a symmetric distribution. This inflammation
causes destruction of cartilage, bone erosion and structural changes
in the joint, which might range from minimal joint damage to debilitating
disease. Patients’ symptoms typically wax and wane, often making
early diagnosis and treatment difficult. Some patients also experience
the effects of rheumatoid arthritis in places other than the joints.
Current Rheumatoid Arthritis Treatments Typically, early stage rheumatoid arthritis is treated with nonsteroidal
anti-inflammatory drugs (NSAIDs), such as the Cox-2 inhibitors Celebrex® and
Bextra®, along with ibuprofen, Naprosyn ®, and Relafen®.
NSAIDs have a limited effect that is only sufficient for a short period
of time, because they simply relieve symptoms without slowing disease
progression.
Diseases modifying anti-rheumatic drugs, or DMARDs, are the only drugs that have
been shown to alter the course of disease. Doctors prescribe DMARDs soon after
diagnosis and for as long as the patient can tolerate the drugs. DMARDs include
antifolates, gold compounds, sulfasalazine, hydroxychloroquine and Tumor Necrosis
Factor, or TNF inhibitors, anakinra and leflunomide and biologic treatments that
alter the course of disease through a variety of mechanisms.
Methotrexate
MTX, a classic antifolate, is the most commonly prescribed DMARD and
is typically the first DMARD prescribed therapy for rheumatoid arthritis.
However, the administration of MTX is known to cause serious side
effects such as pulmonary fibrosis and elevations in liver enzymes,
which can be indicative of early liver and kidney damage.
Leflunomide Leflunomide (Arava®), first marketed in 1998 as new oral
DMARD for the treatment of rheumatoid arthritis, is a cytotoxic that
is believed to work by inhibiting the enzyme dihydroorotate dehydrogenase
(DHODH) to prevent DNA synthesis and limit abnormal cell proliferation.
Side effects include diarrhea, abdominal pain or nausea and altered
liver function.
Biologics
Biologics are usually added to a patient’s treatment regimen
once MTX and other DMARDs are no longer an adequate therapy or side
effects have become unmanageable. The most commonly prescribed biologics,
such as Johnson & Johnson’s Remicade®, Amgen’s
Enbrel® and Abbott’s Humira®, block TNF-a, which is a
pro-inflammatory agent found in large quantities in the rheumatoid
joint. (top)
