Rheumatoid arthritis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]

Overview

There is no known cure for rheumatoid arthritis. However, many different types of treatment can be used to alleviate symptoms and/or to modify the disease process.

Medical Therapy

The goal of treatment in this chronic disease must be two-fold:

• To alleviate the suffering of the patient here and now, and
• To prevent the future destruction of the joints and resulting handicap if the disease is left unchecked.

These two goals may not always coincide: while pain relievers may achieve the first goal, they do not have any impact on the long-term consequences. For these reasons, most authorities believe that RA should be treated, in the vast majority of patients, by at least one specific anti-rheumatic medication, also named DMARD (see below), to which other medications and non-medical interventions can be added as needed.

• Cortisone therapy has offered relief to many patients in the past, but its long-term effects have been deemed undesirable.. However, cortisone injections can be valuable adjuncts to a long-term treatment plan, and using low dosages of daily cortisone (e.g., prednisone or prednisolone, 5-7.5 mg daily) can also have an important benefit if added to a proper specific anti-rheumatic treatment.
• Pharmacological treatment of RA can be divided into disease-modifying antirheumatic drugs (DMARDs), anti-inflammatory agents and analgesics.
• DMARDs have been found to produce durable remissions and delay or halt disease progression.
• In particular they prevent bone and joint damage from occurring secondary to the uncontrolled inflammation. This is important as such damage is usually irreversible.
• Anti-inflammatory drugs and analgesics improve pain and joint stiffness but do not prevent joint damage or slow the disease progression. There is an increasing recognition amongst rheumatologists that permanent damage to the joints occurs at a very early stage in the disease.
• In the past the strategy used was to start with just an anti-inflammatory drug, and assess progression clinically and using X-rays. If there was evidence that joint damage was starting to occur then a more potent DMARD would be prescribed.
• Tools such as ultrasound and MRI are more sensitive methods of imaging the joints and have demonstrated that joint damage occurs much earlier and in more patients than was previously thought. Patients with normal X-rays will often have erosions detectable by ultrasound that X ray could not demonstrate.
• There may be other reasons why starting DMARDs early is beneficial as well as prevention of structural joint damage. In the early stage of the disease, the joints are increasingly infiltrated by cells of the immune system that signal to one another and are thought to set up self-perpetuating chronic inflammation.
• Interrupting this process as early as possible with an effective DMARD (such as methotrexate) appears to improve the outcome from the RA for years afterwards. Delaying therapy for as little as a few months after the onset of symptoms can result in worse outcomes in the long term. *There is therefore considerable interest in establishing the most effective therapy in patients with early arthritis, when they are most responsive to therapy and have the most to gain.
• Treatment also includes rest and physical activity. Regular exercise is important for maintaining joint mobility and making the joint muscles stronger. Swimming is especially good, as it allows for exercise with a minimum of stress on the joints.
• Heat and cold applications are modalities that can ease symptoms before and after exercise. Pain in the joints is sometimes alleviated by oral acetaminophen (paracetamol). Other areas of the body, such as the eyes and lining of the heart, are treated individually. However, there is no diet that has been shown to alleviate rheumatoid arthritis, although fish oil may have anti-inflammatory effects.

Disease modifying anti-rheumatic drugs (DMARDs)

• The term Disease Modifying Anti-Rheumatic Agent was originally introduced to indicate a drug that reduced evidence of processes thought to underly the disease, such as a raised erythrocyte sedimentation rate, reduced hemoglobin level, raised rheumatoid factor level and more recently, raised C-reactive protein level.
• More recently, the term has been used to indicate a drug that reduces the rate of damage to bone and cartilage.
• DMARDs can be further subdivided into traditional small molecular mass drugs synthesized chemically and newer 'biological' agents produced through genetic engineering. Traditional small molecular mass drugs:
  • Azathioprine
  • Cyclosporin (cyclosporine A)
  • D penicillamine
  • Gold salts
  • Hydroxychloroquine
  • Leflunomide
  • Methotrexate (MTX)
  • Minocycline
  • Sulfasalazine (SSZ)
• The most important and most common adverse events relate to liver and bone marrow toxicity (methotrexate, sulfasalazine, leflunomide, azathioprine, gold compounds, D-penicillamine), renal toxicity (cyclosporine A, parenteral gold salts, D penicillamine), pneumonitis (methotrexate), allergic skin reactions (gold compounds, sulphasalazine), autoimmunity (D penicillamine, sulphasalazine, minocycline) and infections (azathioprine, cyclosporine A).
• Hydroxychloroquine may cause ocular toxicity, although this is rare, and because hydroxychloroquine does not affect the bone marrowor liver it is often considered to be the DMARD with the least toxicity. Unfortunately hydroxychloroquine is not very potent, and for most patients hydroxychloroquine alone is insufficient to control symptoms.
• Many rheumatologists consider methotrexate to be the most important and useful DMARD, largely because of lower rates of stopping the drug through toxicity. Nevertheless, methotrexate is often considered by patients and even other doctors as a very "toxic" drug. This reputation is not entirely justified, and at times can result in patients being denied the most effective treatment for their arthritis. *Although methotrexate does indeed have the potential to suppress the bone marrow or cause hepatitis, these effects can be monitored using regular blood tests, and the drug withdrawn at an early stage if the tests are abnormal, before any serious harm is done (typically the blood tests return to normal after stopping the drug).
• In clinical trials in which patients with RA were treated with one of a range of different DMARDs, patients who were prescribed methotrexate were those who stayed on their medication the longest (the others stopped theirs because of either side-effects or failure of the drug to control the arthritis).
• Lastly, methotrexate is often preferred by rheumatologists because if it does not control arthritis on its own then it works well in combination with many other drugs, especially the biological agents. Other DMARDs may not be as effective or safe in combination with biological agents.

Biological agents

Biological agents (biologics include:

• Tumor necrosis factor alpha (TNFα) blockers - etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), golimumab (Simponi)
• Interleukin 1 blockers - anakinra
• Monoclonal antibodies against B cells - rituximab (Rituxan)
• T cell activation blocker abatacept (Orencia)

Anti-inflammatory agents and analgesics

Anti-inflammatory agents include:

• Glucocorticoids: prednisone, meprednisone
• Non-steroidal anti-inflammatory drug (NSAIDs, most also act as analgesics): ibuprofen (sdvil, motrin), diclofenac (cataflam, voltaren), naproxen (naprosync, aleve, anaprox), piroxicam (feldene), Celecoxib (celebrex)

Analgesics include:

• Acetaminophen (Tylenol, Paracetamol outside US)
• Opiates: Tramadol (ultram)
• Diproqualone
• Lidocaine topical

The Prosorba column blood filtering device was approved by the FDA for treatment of RA in 1999 However, in most patients the results have been very modest.

Historic treatments for RA have also included: RICE, acupuncture, apple diet, nutmeg, some light exercise every now and then, nettles, bee venom, copper bracelets, rhubarb diet, rest, extractions of teeth, fasting, honey, vitamins, insulin, magnets, and electroconvulsive therapy (ECT).. Most of these have either had no effect at all, or their effects have been modest and transient in some individual patients, while not being generalizable.