Treatment Of Rheumatoid Arthritis

The fact that there are many anti-inflammatory drugs for RA should not blind patients into the belief that RA could be cured. The very opposite is true! Evidence shows that none of the treatment modalities is curative, but the best the patient can hope for is that the disease process gets more controlled and that the affected joints remain functional. In the following I will briefly summarize the available treatments in a table (gleaned from Ref. 1 and 2) and then comment on each item mentioned in more detail.

Treatment of the initial phase of RA:

COX-2 inhibitors, if the patient can afford it, are likely the drugs of choice as they are not as toxic for the stomach lining or the kidney blood vessels than the regular NSAIDs. With the VIOXX withdrawal from the market there is now a shift in treatment back to the regular anti-inflammatories (NSAIDS).

However, because RA is an autoimmune disease, this type of treatment only suppresses an acute flare-up. We know that untreated RA by itself will settle down in the first year in about 75% of the cases (Ref. 2). General supportive measures such as seeking the advice of a physiotherapist and occupational therapist to get splints made and to preserve as much range of motion as possible through passive exercises followed by active exercises, may be the most important thing to do for the patient. The patient should also use aids and appliances to make the surroundings as comfortable and safe as possible.

Corticosteroids orally or by joint injection, if COX-2 inhibitors alone are not helping, might very quickly settle the arthritis down with a short course of therapy not eceeding 2 weeks. However, if corticosteroids are used for more than 2 weeks, there is an increased risk for osteonecrosis of the hip bone, which would lead to fractures and the need for emergency hip replacements. Other problems of longterm corticosteroid therapy are that the immune system gets paralyzed and serious infections including systemic fungal infections can threaten the life of patients.

Slow acting drugs for second stage:

If after 2 to 4 months there is still no relief from the joint pains and swelling, the patient should seek the advice of a rheumatologist or arthritis center. A decision needs to be made whether to add one of the slow acting drugs to control the inflammation of RA. Popular choices are either gold therapy or sulfosalazine. Each has its advantage and disadvantage.

Gold therapy, for instance, can sometimes show impressive results with initial injections of gold (sodium aurothiomalate). However, longterm treatment with gold is not tolerated as well and toxic effects of gold therapy are becoming more evident as time goes on and gold accumulates in the system. Patients with liver or kidney disease are not allowed to get gold therapy as gold itself affects liver (hepatitis) and kidneys (nephrotic syndrome) negatively. Bone marrow suppression is another danger.

Sulfasalazine, which has been used for a long time for ulcerative colitis is often used now for RA. It may take up to 3 months before the full effect of this agent is visible in terms of improvement of joint swelling and pain. Side effects are gastric irritation, bone marrow suppression, anemia due to hemolysis and a skin rash. The rheumatologist will want to monitor the blood values closely while on this therapy. About 60% of patients put on this medication can still tolerate it after 3 years, but about 15% will have to stop it because of toxic side effects (Ref.1).

Hydroxychloroquine is an old anti-malarial drug that has been found in the past to be beneficial for RA patients. It is perhaps better tolerated, but it has one serious side effect, which limits its use: retinal damage due to an irreparable retinal degeneration. The rheumatologist likely will want to have an ophthalmologist examine the patient every 6 months while this medication is used. When the RA has stabilized, the minimum possible maintenance dosage is used to minimize risk (Ref.2).

Penicillamine is sometimes used by the rheumatologist when gold therapy fails. However, side effects are more common than with gold therapy and include toxicity to the bone marrow, kidneys (nephrosis), nervous system (myasthenia gravis), skin (pemphigus), muscles (polymyositis) and a lupus like syndrome. If this medication is used, then the specialist will have to carefully monitor for these side effects with ongoing blood tests (Ref. 1 and 2). A metallic taste and nausea are common, but often disappear with continued use.

Use of immunosuppressive drugs for resistant RA cases:

If the other measures were unable to provide relief to the RA sufferer, the we are dealing with a particularly severe case of RA. The RF titer likely is very high and the C-reative protein as well. This means that the autoimmune bodies and the resulting immune complexes that are formed throughout the body continue to irritate the synovial membranes leading to more and more synovitis as well as joint and ligament destruction. In these cases it would theoretically make sense to dampen the immune system to control the RA. However, we are only at the beginning to learn how to this therapy without harming the rest of the body.

Methotrexate is one of the more popular medications. It is an anti-cancer agent and like all these chemotherapeutic agents has a bone marrow suppressant side effect. It cannot be used in patients who have a history of heavy alcohol consumption or in diabetics. Liver function must be monitored. Immune supression leads to sometimes serious viral or bacterial infections that can be life threatening. However, with low dose intermittent methotrexate therapy some patients can be well controlled with their RA (Ref.2).

Cyclosporine is the medication that is used to suppress the rejection of a trasplanted organ. The reason it can be useful for RA patients is that the autoimmune antibody production that leads to RF can be supressed with this medication. However, it is costly, and it has a toxic kidney effect that leads to high blood pressure. On the other hand it does not have the bone marrow toxicity that other agents have (Ref. 1). Other side effects are a tremor, excessive gum growth (gingival hypertrophy), increased hair growth and interaction with a large number of drugs.

Azathioprine seems to be useful when synovitis (swelling of the joint lining) is a prominent feature in RA. However, bone marrow and liver toxicity limit its use as well as the danger of development of a lymphoma with prolonged use (Ref. 1).

Cyclophosphamide is another chemotherapeutic drug that is used in certain cancers. It is somteimes used for very resistant RA cases where severe synovitis or vasculitis is resistant to other treatment modalities. However, like with methotrexate the rheumatologist must be careful to monitor vital organ functions (Ref.1).

Newer approaches to treatment

Many of the anti-aging physicians in Ref. 11 point out that rheumatoid arthritis is not only an inflammation of the joints, but also a problem where toxic substances such as heavy metals have accumulated over a long period of time. Intravenous chelation therapy can be used to remove some of these toxic metals. In addition Ref. 11 points out that hormone rebalancing may be required (special blood tests or saliva tests can be ordered by an anti-aging physician who is knowledgeable in bioidentical hormone replacement). Often there are a number of hormone deficiencies that get overlooked, such as hypothyroidism and a lack of sex hormones (estrogen, progesterone, but also DHEA and testosterone). In older persons there often is a lack of human growth hormone, which can be measured by doing IGF-1 blood tests (an indicator hormone from the liver that gets stimulated by growth hormone from the pituitary gland). At the 19th Annual World Congress Anti-Aging and Aesthetic Medicine in Las Vegas (December 8-10, 2011) Dr. Hertoghe pointed out in several presentations that hormone production of our hormone glands is diminishing throughout our lives. In rheumatoid arthritis patients this may occur at a much younger age. The good news is that replacement of whatever hormone is missing by bio-identical horomones makes the patients painfree and helps them to remobilize.

There is a consensus recently that RA responds best, if it is treated more aggressively right in the beginning before the abnormal autoimmune reaction has progressed too much. O'Dell reports in Ref.3 that RA , which does not respond to methotrexate alone, will often respond well to a combination of methotrexate with cyclosporine or combination of methotrexate with leflunomide.

Leflunomide is one of the newer disease modifying agents described in Ref. 4. It prevents the proliferation of activated lymphocytes by inhibiting a specific enzyme. Leflunomide is as effective as sulfasalazine or methotrexate. It improves physical function, prevents erosions on x-rays and improves quality of life (Ref. 4).

Other promising studies have shown that inhibition of the cytokine, tumor necrosis factor (TNF), through specific monoclonal antibodies (infliximab, etanercept and others ), will improve the clinical response. They are given by repeated infusions in intervals for infliximab (brandname: Remicade) or by subcutaneous injection twice per week with etanercept (brandname: Enbrel). Occasionally the rheumatologist may combine one of these agents with methotrexate and it can be more effective this way (Ref. 4 and 5), but at the same time side effects such as various types of infections also become more common. According to the authors of Ref. 6 the immunomodifiers that inhibit TNF are a turning point in the therapeutic management of RA.

Food supplements have been used for a long time for RA, although they are not too useful in active treatment, they might have an important place in terms of prevention. There is the theory that a lot of arthritis, if not all of it, has something to do with the syndrome of insulin resistance (now more aften referred to as "metabolic syndrome" and the lack of omega-3 fatty acids in our modern diets, which are rich in sugar and starch (see Ref. 7).

This theory is supported by the observation that high insulin levels dysbalance the ecosanoid metabolism, which results in more cytokines like TNF that can cause arthritis. By avoiding intake of refined sugar and too much starch the insulin level can return to normal levels and by adding omega-3 fatty acids (evening primrose oil, fish oil) and extracts from New Zealand green lipped mussels the natural anti inflammatory properties of these food supplements can be utilized to strengthen the immune system. Ref. 8 is useful guide in terms of starting a zone type diet, where these principles are utilized. However, I am suggesting that patients with RA see a rheumatologist as well so that these latest immune modifiers mentioned above can also be taken, if the specialist thinks that this is necessary. The key is to stop the inflammatory autoimmune process that eats away the cartilage and bone around the joints in the body (erosive lesions adjacent to the joint on X-rays and periarthritic osteoporosis).

One interesting observation is that calorie restriction can improve RA on the short term (Ref. 1,p.47). It was speculated that his may mean that certain foods are allergenic and if they would be avoided, RA would get better. Others say that the extra calories lead to hyperinsulinism and the dysbalance of cytokines mentioned above. There may be a combination of several factors.

Disclaimer:

This outline is only a teaching aid to patients and should stimulate you to ask the right questions when seeing your doctor. However, the responsibility of treatment stays in the hands of your doctor and you.

References:

1. ABC of rheumatology, second edition, edited by Michael L. Snaith , M.D., BMJ Books, 1999. Chapter 10.

2. The Merck Manual, 7th edition, by M. H. Beers et al., Whitehouse Station, N.J., 1999. Chapter 50.

3. J O'Dell  J Rheumatol Suppl 2001 Jun;62:21-26.

4. ET Koh  Ann Acad Med Singapore 2001 Mar;30(2):170-173.

5. AJ Ostor et al. Aust Fam Physician 2001 Apr;30(4):314-320.

6. C Richard-Miceli et al. BioDrugs 2001;15(4):251-259.

7. B. Sears: "The age-free zone".Regan Books, Harper Collins, 2000.

8. B. Sears: "Zone perfect meals in minutes". Regan Books, Harper Collins, 1997.

9. Ferri: Ferri's Clinical Advisor: Instant Diagnosis and Treatment, 2004 ed., Copyright © 2004 Mosby, Inc.

10. Rakel: Conn's Current Therapy 2004, 56th ed., Copyright © 2004 Elsevier

11. Suzanne Somers: "Breakthrough" Eight Steps to Wellness-- Life-altering Secrets from Today's Cutting-edge Doctors", Crown Publishers, 2008

Last Modified: March 22, 2012