Rheumatoid arthritis is a chronic disorder for which there is no known cure. Fortunately in the last few years, a shift in strategy toward the earlier institution of disease modifying drugs and the availability of new classes of medications have greatly improved the outcomes that can be expected by most patients. The goal of treatment now aims toward achieving the lowest possible level of arthritis disease activity and remission if possible, minimizing joint damage, and enhancing physical function and quality of life. The optimal treatment of RA requires a comprehensive program that combines medical, social, and emotional support for the patient. It is essential that the patient and the patient’s family be educated about the nature and course of the disease. Treatment options include medications, reduction of joint stress, physical and occupational therapy, and surgical intervention.
There are three general classes of drugs commonly used in the treatment of rheumatoid arthritis: non-steroidal anti-inflammatory agents (NSAIDs), corticosteroids, and disease modifying anti-rheumatic drugs (DMARDs). NSAIDs and corticosteroids have a short onset of action while DMARDs can take several weeks or months to demonstrate a clinical effect. DMARDs include methotrexate, sulfasalazine, leflunomide (Arava®), etanercept (Enbrel®), infliximab (Remicade®), adalimumab (Humira®), certolizumab pegol (Cimzia®), golimumab (Simponi®), abatacept (Orencia®), rituximab (Rituxan®), tocilizumab (Actemra®), anakinra (Kineret®), antimalarials (e.g. Plaquenil®). Other immunomodulators are occasionally used including azathioprine (Imuran) and cyclosporine. Because cartilage damage and bony erosions frequently occur within the first two years of disease, rheumatologists now move aggressively to a DMARD agent early in the course of disease, usually as soon as a diagnosis is confirmed. are also sometimes helpful in decreasing pain until DMARDs take effect. A summary table of how to monitor drug treatment in rheumatoid arthritis is included.
Non-steroidal Anti-inflammatory Agents (NSAIDs)
The major effect of these agents is to reduce acute inflammation thereby decreasing pain and improving function. All of these drugs also have mild to moderate analgesic properties independent of their anti-inflammatory effect. It is important to note however that these drugs alone do not change the course of the disease of rheumatoid arthritis or prevent joint destruction.
Aspirin is the oldest drug of the non-steroidal class, but because of its high rate of GI toxicity, a narrow window between toxic and anti-inflammatory serum levels, and the inconvenience of multiple daily doses, aspirin’s use as the initial choice of drug therapy has largely been replaced by other NSAIDs. There are a large number of NSAIDs from which to choose, and at full dosages all are potentially equally effective. Likewise, the toxicities of the currently available NSAIDs are similar. However, there is a great deal of variation in tolerance and response to a particular NSAID. Many different NSAIDS are available, some over the counter including ibuprofen (Advil ®, Motrin®, Nuprin ®) and naproxen (Alleve®) and many others are available by prescription including meloxicam (Mobic®), etodolac (Lodine®), nabumetone (Relafen®), sulindac (Clinoril®), tolementin (Tolectin®), choline magnesium salicylate (Trilasate®), diclofenac (Cataflam®, Voltaren®, Arthrotec®), diflusinal (Dolobid®), indomethicin (Indocin®), ketoprofen (Orudis®, Oruvail®), meloxicam (Mobic®), oxaprozin (Daypro®), and piroxicam (Feldene®). Longer acting NSAIDs that allow daily or twice daily dosing may improve compliance. The NSAID class also includes drugs known as COX-2 inhibitors that are also effective in controlling inflammation. Only one of these agents is currently available in the United States (celecoxib, Celebrex®) while additional compounds are available in other countries (etoricoxib, Arcoxia®; lumiracoxib, Prexige®). These drugs were designed to decrease the gastrointestinal risk of NSAIDS, but concerns of possible increases in cardiovascular risk with these agents has led to the withdrawal of two of these drugs from the market (rofecoxib, Vioxx®; valdecoxib, Bextra®).
NSAIDs inhibit the generation of prostaglandins by blocking cyclooxygenase enzymes, COX-1 and COX-2. Prostaglandins are mediators of inflammation and pain but also have important roles in maintenance of normal body functions including protection from stomach acid, maintenance of kidney blood flow, and contributing to platelet stickiness and vascular function. COX-2 selective inhibitors selectively block prostaglandins generated via COX-2 which have prominent roles in inflammation.