Arthritis simply means inflammation in a joint but Rheumatoid Arthritis is a chronic joint disease that causes inflammation, usually in peripheral joints such as finger joints, wrist and knees which occur on both sides of the body. It also causes inflammation of the synovial membrane (lining of the joints) and may affect other organs too. In addition, it is also an autoimmune disease which implies that the body's immune system mistakenly attacks its healthy tissues and that clearly differentiates Rheumatoid Arthritis from other types of Arthritis. The common manifestations are joint pain, swelling, stiffness and fatigue and if left untreated, this will lead to bone erosion and permanent bone deformity. Worldwide, the annual incidence rate of Rheumatoid Arthritis is approximately 3 cases per 10000 populations and the prevalence rate is approximately 1%.1Moreover, women are two to three times more prone to this disease than men. The actual cause of Rheumatoid Arthritis is still unknown but a combination of several factors like genetic, environment and hormones may play a part. It is admitted that there is presently no known cure for Rheumatoid Arthritis, however, it can be treated. Thus, what are the possible treatments?
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Figure 1 Normal joint and Rheumatoid Arthritis joint (Source: http://www.medicinenet.com/rheumatoid_arthritis/article.htm#1whatisra)
A Possible Solution
Early aggressive treatment for Rheumatoid Arthritis is essential to avoid further joint deformity. The goal of the treatment is to minimize the symptoms and inflammation, hence drugs are normally prescribed to patients.1,2,4 The most common drugs prescribed to patients are non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying antirheumatic drugs (DMARDs).
This pie chart shows different classes of treatment with corresponding percentages. Conventional DMARDs are used 46% of the time, NSAIDs are used 6%, Placebo is 18%, Steroids are 2%, Biological DMARDs are 6%, a combination of treatments is 9%, and other drugs constitutes for 14% (Source :http://www.metawork.com).
Non-steroidal anti-inflammatory drugs (NSAIDs)
This drug reduces the symptoms of RA but it does not stop the joint damage so, additional medications are required to prevent the progress of RA.1.2When the tissues are damaged, they release a chemical liked hormone called prostaglandins. It is this chemical that promotes inflammation, pain and the rest of the symptoms. This chemical is produced by two types of cyclooxygenase (COX) enzyme named COX-1 and COX-2. Therefore, NSAIDs inhibit the action of these enzymes to lessen the production of prostaglandins hence reducing the symptoms.5 Examples of NSAIDs include aspirin, celecoxib (COX-2 inhibitor), diclofenac, ibuprofen, meloxicam and naproxen.6 RA symptoms peaks during the night and at the time of awakening, so these drugs are best taken after the evening meal (reduces stomach discomfort) and on awakening.8
However, NSAIDs have many side effects that should be considered before it is prescribed. This will be discussed later. So, NSAIDs cannot be given to patients who are;
allergic to aspirin or any NSAIDs
diagnosed with active peptic ulcer
on anticoagulants (blood thinning agents)
treated for fractures7
"Aspirin is the only one that is proven to offer significant protection against heart disease by interfering with blood clot formation and probably acting in other ways we do not understand. If ibuprofen is taken also, studies have shown that it can lessen the effectiveness of an aspirin regimen. Most experts believe an occasional ibuprofen for, say, a headache should not significantly interfere with the heart protective effect of regular aspirin."
(Source : http://www.faqs.org/abstracts/Health/Drugs-for-rheumatoid-arthritis.html)
This graph shows how patients rated effectiveness of paracetamol compared with NSAIDs (Source: http://www.medicine.ox.ac.uk/bandolier/band76/b76-5.html).
Based on this graph, NSAIDs are more effective than paracetamol because 62% agree that paracetamol is less effective than NSAIDs that more patients opt for them. Hence, NSAIDs are appropriate for pain relief in the case of Rheumatoid Arthritis.
Disease Modifying Anti-rheumatic Drugs (DMARDs).
These slow-acting medicines act in many different ways but they are common in interfering with the immune processes that causes inflammation hence slowing or stopping the progression of Rheumatoid Arthritis.1 It is not understood how this works but they are not selective in their targets. Moreover, this decreases the overall immune system and increases the probabilities of other infections.2 DMARDs are very effective for long term control of symptoms as they take about six to eight months of treatment to see the results.9 Just like NSAIDs, these drugs are better when combined with other drugs. Some examples of these drugs are methotrexate, azathioprine and cyclosporine.
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Methotrexate is the most commonly used DMARD as it has infrequent side effects and works faster than many other DMARDs. This drug alleviates most of the symptoms for rheumatoid arthritis. Even though it is not clear how this works, it is believed that it affects the immune system.10 "A 2002 study suggested that it reduced mortality rates from heart disease by 70% compared to other DMARDs" (http://adam.about.com/reports/000048_7.htm). In addition, methotrexate works the best when combined with other DMARDs or agents. Aggressive treatment as the combination of DMARDs is effective for patients who do not respond successfully or have built up resistance to methotrexate or other drugs alone.11Since these combinations are quite safe and have low level of toxicity; patients are encouraged to try this approach. All these require a regular check-up to see whether the treatment is working and to be adjusted as needed.12
"The Finnish Rheumatoid Arthritis Combination Therapy (FIN-RACo) trial compared combination DMARDs with monotherapy DMARD in patients with early RA who had fewer than 2 years of disease duration." (Source : http://cme.medscape.com/viewarticle/520167_3). This shows thatÂ a combination of DMARDs is more effective in controlling rheumatoid arthritis.
Ethical and Social Implications
It is unethical that some patients are not well informed of the risk of adverse effects of the prescribed medications. The patients' willingness to accept the risk is very important because this is regarding their lives so they should be given full explanation on that. Moreover, some patients might not be willing to take the medications appropriately as they do not want to jeopardise themselves. According to the journal "Rheumatology" (Source : http://rheumatology.oxfordjournals.org/content/41/3/253.full), 33% of the patients were not willing to accept the risk of adverse effects related to the prescribed medications.
Patient willingness to take medications associated with specific adverse effects
Figure 4 (Willingness was measured on an anchored VAS on which 0='not willing under any circumstances' and 100='definitely willing'. N/V, nausea and vomiting.)13
Based o the graph, more patients were willing to accept the risk of reversible cosmetic changes than temporary discomfort while least patients are willing to take medications associated with a risk of major toxicity. Therefore, I believe that patients and doctors should discuss and decide the best medicine for them. However, patients can also opt for other safer treatments with less risk of adverse affects.
"The direct medical costs of rheumatoid arthritis approach $5 billion annually, with nearly 70% of these costs attributable to hospitalizations and home nursing care.14,15 Rheumatoid arthritis patients make more than 9 million physician visits and account for over 250,000 hospitalizations annually.16 The direct cost to patients is considerable, even with insurance." (Source : http://www.remicade.com/remicade/global/hcp/hcp_ra.html#Implications )
This would cause a huge financial burden to the poor families. Patients who have sought treatment via medications might lose their jobs due to crippling effects of the disease, hence resulting in lost of wages. Besides that, combining medicines is also costly despite its effectiveness and lesser adverse effects. Therefore, I would suggest the government to subsidise the medications for poor families. However, some people might argue that the exorbitant amount of money should not be used to treat an incurable disease like rheumatoid arthritis. Nevertheless, this issue can be solved if their social welfare is balanced as well.
Benefits and Risks of NSAIDS and DMARDs
Rheumatoid Arthritis medications can help to reduce inflammation as well as slow or stop the progress of the incurable disease. So, it is easy for patients to carry out daily tasks without pain and any difficulties. This can better enhance the quality of life. Besides that, most medicines come in the forms of pills and injections. I personally think that it is easier and safer for patients to consume them besides being non-invasive. Moreover, patients do not have to travel to and fro the hospital to get daily supplements of medications. However, they need frequent check-ups to check on the effectiveness of the prescribed drugs. In addition to that, it is often difficult to find the best drug for any one patient.17
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The prostaglandins that are blocked by NSAIDs give protection against stomach acid, maintains the kidney blood flow, platelet stickiness and cardiovascular functions.18As the chemicals are lessen in the body, gastrointestinal bleeding (due to inference of clotting function of platelets) and other symptoms such as stomach iritation may occur as well as ulcer. These symptoms can be reduced by taking medicine with food but do not affect the risk of bleeding.18Besides that, NSAIDs also impairs renal function that can increase blood pressure which eventually damages the kidneys. "In a University of Massachusetts Medical School study of 4,099 people over age 70, investigators found warning signs ofÂ kidney failureÂ among those who used NSAIDs regularly". (Source:http://healthlibrary.epnet.com/GetContent.aspx?deliverycontext=&touchurl=&CallbackURL=&token=1edc3d6e-4fec-4b20-baca-795e48830daa&chunkiid=13372&docid=/healthy/aging/1999/nsaids/index)
This increased blood pressure can therefore cause heart attack and stroke.
As for DMARDs, it takes weeks or even months to show the effects. This would waste a lot of the treatment time if the medications prescribed are ineffective. By the time the effective medications were recognised, the progression of rheumatoid arthritis might become even worse. Generally, methotrexate can scar the liver and eventually induce liver disease but this affects 1 in 1000 rheumatoid arthritis patients over a 5-year period of treatment.17Besides that, it also suppresses the production of red blood cells, white blood cells and platelets19 that blood count should be done for every 2 months. Other side effects are inflammation in the mouth and nausea and diarrhoea which can be overcome by taking this medication at night. In order to reduce the toxicity, folic acid will be given which does not affect the effectiveness of methotrexate.
It is usually used with medications and can be effective in halting the progression of rheumatoid arthritis. As for me, this can be an alternative for NSAIDs because it also relieves pain besides being safe, cost effective and has no toxicity. Therapist assigns range of motion exercises and programme to delay the lost of joint function4, thus patients are able to move around as normal. Moreover, it increases strength of the muscles surrounding the affected joints. The benefits of this therapy are patients are well-informed and educated about their conditions besides learning to curb discomfort and improve performance. So, they can control the symptoms even at home.3,20
Therapeutic modalities are normally used as part of the therapy that includes hot and cold therapies. Both relieve chronic pain and muscle stiffness. Cold therapy is given via cold ice packs, ice sticks, spray and ice water1 that reduce swelling while hot therapy is by hot packs, hot shower and spas. Basically, these relax muscle spasm and provide better blood flow to the affected area.3, 20 It is believed that heating joints and muscles can help patients to exercise easily.
The cornerstone of physical therapy is exercise which improves flexibility, strength and joint movement. Figure 5 shows the correct way of exercising to strengthen muscles when joints are inflamed. Physical therapist will choose the best regime to help the patients.21
Figure 5 (Source: http://www.arthritisnaturaltreatments.com/rheumatoid-arthritis-natural-treatments-diet-and-exercise)
When medications are not effective and disease is becoming more severe, surgery is the best option. It reduces pain and improves joint functions although it can be costly. In order to reduce the risk of complications, patients are advised to exercise, stop smoking and practise a balanced and healthy diet.2 Besides that, some prescribed drugs that cause immune system suppression will be stopped to prevent any infection thus reducing their adverse effects. This surgical procedure is complex and can be divided into joint replacement, tendon reconstruction and synovectomy.
Joint replacement relieves pain by removing part of the damaged joints (normally in hips and knees) and replacing them with artificial joints. Usually, prosthesis is composed of chromium alloy, plastic (for patients allergic to metals) or porous metals.22 As only smaller incisions are made, recovery time is shorter and leaves almost no scar. However, the artificial joints have to be replaced over time. During surgery, patient may suffer from major blood lost so they need to donate blood before surgery for transfusion.23
Tendons are tissues that attach muscle to bone and the damaged tendons can be reconstructed by tendon reconstruction where intact tendons are attached to it.24 As for synovectomy, it removes the inflamed synovial tissue but the effect is transient. It is less preferred for the tissues are not fully removed and can grow back.
Figure 6 Artificial knee joint (Source: http://www.centerforjointreplacements.com/images/2B11416-big.jpg)
14Yelin E. The costs of rheumatoid arthritis: absolute, incremental, and marginal estimates.Â J Rheumatol. 1996;23(suppl):47-51.
15Â Jacobs J, Keyserling JA, Britton M, et al. The total cost of care and the use of pharmaceuticals in the management of rheumatoid arthritis: the Medi-Cal program.Â J Clin Epidemiol. 1988;41:215-223
16American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Guidelines for the management of rheumatoid arthritis.Arthritis Rheum. 1996;39:713-722.