Health and Pills

Archive for the ‘Arthritis’ Category

New Therapeutic Advances

Recently, many new agents to treat rheumatoid arthritis have been developed or are under investigation. Traditional antirheumatic drugs suppress the inflammatory response and slow the process of joint destruction. Yet the mechanisms of action for these drugs are nonspecific. Newer drugs have been designed to target the inflammatory process and specific components in the inflammatory cascade. The newer biotechnology agents have been designed to target components of the immune system involved in inflammation, while preserving the integrity of the immune system to fight off infection. Another relatively new approach is the use of combination therapy with various DMARDs in the hope that combining drugs with different mechanisms of action will provide added benefit.

Cox Inhibitors: The variation in GI side effect profiles of NSAIDs may be due to the COX selectivity of individual drugs. COX serves as the rate-limiting enzyme in prostaglandin production. Inhibiting this enzyme decreases prostaglandin-induced initiation and maintenance of inflammatory responses. Two isoforms of COX have been identified (COX-1 and COX-2).27 COX-1 is beneficial in helping to maintain normal cellular physiologic processes in the GI tract, kidneys, and blood. In the gut, COX-1 stimulates the secretion of bicarbonate and mucus, and reduces stomach acid secretion. All of these actions are protective for the lining of the stomach against irritants. COX-2 is involved in selectively activating pro-inflammatory cytokines and does not have a gastroprotective effect. Therefore, the ideal agent would selectively inhibit COX-2 to reduce the inflammatory response but also maintain the GI and renal protective nature of COX-1.29 NSAIDs have been developed to be COX-2 selective, or combined with synthetic prostaglandins to minimize GI intolerance. Of the NSAIDs on the market, etodolac (Lodine) and nabumetone (Relafen) are the most selective agents for COX-2 and have the lowest incidence of GI and renal side effects. Piroxicam (Feldene), indomethacin (Indocin), naproxen (Naprosyn), and sulindac (Clinoril) have a greater affinity for inhibiting COX-1 and therefore an increased risk of GI and renal problems. Flurbiprofen (Ansaid), ibuprofen (Motrin), meclofenamate sodium (Meclomen), and diclofenac (Voltaren) show equal affinity for COX-1 and COX-2 inhibition. While the clinical relevance of COX-2-selective NSAIDs is unclear, these agents may prove beneficial in patients requiring long-term NSAID therapy who are predisposed to developing adverse GI effects. COX-2 selective agents would inhibit the inflammatory response but maintain the GI protective properties of COX-1. Studies using one of the first COX-2 inhibitors, meloxicam, demonstrated that selectively inhibiting COX-2 improved GI tolerability while maintaining therapeutic effectiveness. An FDA advisory panel has recommended approval of Celecoxib (Celebra), which in Phase III trials shows promising results for pain reduction and joint swelling. In a clinical trial enrolling 300 patients with active RA, celecoxib was administered to patients experiencing an acute flare. Patients given either 200 mg BID or 400 mg BID had a statistically significant improvement. Patient global assessment scores, duration of morning stiffness, and number of painful or tender joints all improved compared to placebo. A COX-2 inhibitor by the name of Vioxx will be undergoing clinical trials in late 1998. Preliminary research shows a significant improvement in preventing GI mucosal damage when compared to aspirin and ibuprofen.

Biotechnology: Biotechnology is playing an increasing role in the development of novel approaches to manage rheumatoid arthritis. Molecular technology has permitted the identification of specific cell components and cell surface markers that contribute to the immune-mediated response in rheumatoid arthritis. Although the etiology of rheumatoid arthritis remains unknown, this increased understanding of the pathogenesis provides opportunities to target the immune system with specific therapies. Several biologic agents developed for the treatment of rheumatoid arthritis include monoclonal antibodies, recombinant interleukin-1 receptor antagonists, and recombinant soluble tumor necrosis factor receptor.

The role of cytokines in rheumatoid arthritis is a concept that has been explored for many years. Identifying a T-cell mediated immune response was the first step in targeting the inflammatory response in rheumatoid arthritis. The concept of activated T-cells both initiating rheumatoid synovitis and maintaining chronic RA has focused new attention on specific pro-inflammatory cytokines such as IL-1 and TNF-a. These cytokines are believed to be directly responsible for the clinical manifestations of rheumatoid arthritis, and therapies are being developed to specifically target these areas.

Monoclonal Antibodies: Monoclonal antibodies (MAbs) have been developed to bind to receptors on the surface of T-cells, thus interfering with their function or making the T-cells unavailable for binding. By binding to T-cells, MAbs disable the autoimmune response involved in inflammation and tissue destruction. This may slow the disease progression. Some trials of monoclonal antibodies (MAbs) have shown a resultant reversible depletion of T-cells that would prevent the patient from mounting a T-cell mediated immune response. IDEC Pharmaceuticals and SmithKline Beecham have partnered to develop a chimeric combination of human and monkey antibodies. This agent has proven to be less allergenic than previous products made with mouse antibody. Phase II trial results indicate an improvement >20% by American College of Rheumatology criteria in 42%–47% of patients receiving therapy with 40 mg and 80 mg, respectively. Dosages of 140 mg were also evaluated but had to be discontinued due to the development of rash. No other adverse effects were reported, and rash was not observed in patients receiving the lower dosages. Patients receiving this therapy sustained benefit for 2–3 months following discontinuation before arthritis symptoms worsened.
Other MAbs are being developed, such as an antibody that would be coupled with a cytotoxin that, when taken up into the target cell, would cause cell destruction and decrease the immune response. No agents are currently available using these techniques.

Cytokines: Tumor necrosis factor alpha (TNF-a) and interleukin-1 (IL-1) are two proinflammatory cytokines that appear to be dominant in the inflammatory response in rheumatoid arthritis. In patients with rheumatoid arthritis, there is an imbalance between proinflammatory and anti-inflammatory mediators, which may or may not be cytokines. This leads to increased activity of the proinflammatory components (TNF-a and IL-1) and inflammation at the site. By providing exogenous inhibitors such as antagonists or antibodies or soluble receptors, one may achieve an anti-inflammatory state within the joint. When administered over 6 months to patients with rheumatoid arthritis, IL-1 receptor antagonists have been shown to decrease C-reactive protein, as well as improve responses based on American College of Rheumatology clinical response criteria. Monoclonal antibodies to TNF provided the first evidence that TNF inhibitors may be useful agents in treating rheumatoid arthritis. Both open-label and double-blind, placebo controlled trials using MAbs to TNF have demonstrated significant decreases in CRP levels and number of swollen joints. Agents used to inhibit the activity of TNF-a and IL-1 have only been used as monotherapy. Combination biologics is in its infancy at this time.

TNF Receptors: The identification and isolation of soluble TNF receptors (sTNFRs) is also being pursued. sTNFRs are a naturally occurring counter-regulation mechanism to the activity of TNF. Levels of soluble receptors are elevated in both plasma and synovial fluid samples of rheumatoid arthritis patients and patients with other autoimmune and inflammatory conditions. A recombinant human TNFR fusion protein (TNFR:Fc) has been developed by Immunex to neutralize TNF. Etanercept (Enbrel) is a product of recombinant DNA technology in which the extracellular portion of two TNF receptors is linked to the Fc fragment of human IgG1 molecules and then expressed in mammalian cells. The product acts as a noncompetitive inhibitor of TNF, preventing binding of TNF to the cell surface receptor, thus reducing TNF activity.
Both Phase II and Phase III clinical trials have been conducted using etanercept. Etanercept was administered as 10–25 mg SC twice weekly. Subjects had active RA and had failed to respond to therapy with DMARDs at least once. Results show a statistically significant reduction in disease activity, which was determined using clinical endpoints (American College of Rheumatology clinical response criteria); biological markers (CRP, ESR); and quality of life assessments (health assessment questionnaire, visual analog pain scale). Clinical improvement was seen in these areas within 2 weeks of initiating therapy. Treatment was generally well tolerated, with the most common side effect reported as redness and discomfort at the injection site. There appeared to be an increased incidence of upper respiratory tract infections in patients receiving etanercept; however, this difference was not significant when the data was analyzed over time.

Soluble cytokine receptors such as etanercept may have a therapeutic advantage over other TNF agents since immunogenicity does not appear to be an issue. Nonhuman or chimeric MAb therapy often stimulates the production of antibodies which deactivate the therapeutic agent, limiting long-term use or inducing allergic reactions. In the previously mentioned Phase II and III studies involving etanercept, neutralizing antibodies were not detected. The information gathered on etanercept is promising in its therapeutic applications in rheumatoid arthritis. At press time etanercept was recommended for approval by the FDA arthritis advisory committee as a mono agent or in combination for the treatment of active rheumatoid arthritis.

Immunosuppression: Suppressing the immune response to a particular antigen can be induced by oral administration of certain antigens. This may be beneficial in treating rheumatoid arthritis since oral administration of antigens including collagen have been shown to be effective in blocking the induction of, or ameliorating, established disease. Proposed mechanisms of action include induction of anti-inflammatory cytokines (i.e., IL-4 and IL-10) and the stimulation of growth factor at the site of joint injury. Several studies have investigated oral collagen. Patients given chicken type II collagen showed statistically significant improvements in the number of swollen or tender joints while patients receiving bovine type II collagen showed only minor clinical response. More controlled trials are needed to evaluate the efficacy of orally administered type II collagen in treating rheumatoid arthritis.
Immunosuppressive agents are another growing area of development in treatments for rheumatoid arthritis. Leflunomide (Arava) is an isoxazole derivative similar to methotrexate. Current studies with the drug are focused on treating autoimmune diseases such as rheumatoid arthritis. The mechanism of action of leflunomide is not completely known; however, it is believed to interfere with T-cell proliferation, which then inhibits synthesis of pyrimidines. This decrease in pyrimidine synthesis leads to a reduced number of proinflammatory cytokines within the body. The mild anti-inflammatory effect seen with leflunomide may be attributed to this activity.
Leflunomide dosing is one 100 mg tablet daily for three days, followed by a maintenance dose of one 20 mg tablet each day. Data on the use of leflunomide in patients with RA are promising. Both Phase II and Phase III double-blind, placebo-controlled, clinical trials showed statistically significant improvement versus placebo. Patients receiving leflunomide had a decreased number of tender or painful joints, improved global patient assessment scores, and improved clinical response criteria. Clinically significant results were seen after 1 month of therapy and benefit was retained for up to 18 months. Side effects associated with leflunomide include diarrhea, reversible alopecia, and hypertension. Six percent of patients discontinued therapy due to these side effects. Leflunomide has now been approved by the FDA for the treatment of inflammatory arthritis. This new agent will provide yet another approach to treat RA and add to possible combination therapies with other DMARDs.

Combination Therapy: By combining several drugs with different mechanisms of action, a greater benefit may be achieved than if the same drugs were used independently. It may also be possible to use lower doses of the medications, therefore minimizing the toxicities associated with each drug. Combinations of DMARDs that have been evaluated in the literature include MTX and HCQ; MTX, AZA, and HCQ; MTX and gold; MTX and cyclosporin A; MTX and SSZ; MTX, SSZ, and HCQ; HCQ and cyclosporin A; and MTX and DP. Studies indicate that the combination of antimalarials and DP shows antagonism within the body. While the effectiveness of combination therapy is difficult to evaluate, these therapies have provided relief when other medications used alone failed to do so.

Rheumatoid arthritis: Conclusion

New therapies and modifications on old therapies are constantly being explored in order to improve the treatment of rheumatoid arthritis. As more is learned about the disease process and the pathophysiology behind it, improved, targeted therapies can be developed. While there is no cure yet for rheumatoid arthritis, the future is promising for finding the treatments necessary to control and suppress the disease, enabling rheumatoid arthritis patients to continue to work and more comfortably perform their daily activities.

Nonsteroidal Anti-inflammatory Drugs

OTC NSAIDs are indicated for self-treatment of pain rather than inflammation, and the dosing guidelines on the package should not be exceeded unless the patient is instructed to do so by a physician. Patients taking OTC products should be closely monitored for effectiveness of therapy and the development of toxicities. NSAIDs are the initial drug treatment of choice for rheumatoid arthritis since they work to reduce joint pain and swelling, and improve function. While their analgesic and anti-inflammatory properties provide benefit, NSAIDs do not alter the course of rheumatoid arthritis or prevent joint destruction. Their mechanism of action is related to the inhibition of prostaglandin (PG) synthesis. Cyclooxygenase (COX) serves as the rate-limiting enzyme in PG production. Inhibition of this enzyme decreases PG-induced initiation and maintenance of inflammatory responses. There is no significant clinical difference in efficacy among the NSAIDs, although patient response to individual agents varies greatly. The choice of NSAIDs should be based on cost, duration of action, and patient tolerability and acceptance. While the analgesic effect of NSAIDs is quick in onset, the anti-inflammatory effect may not be complete for 4–6 weeks. If a patient fails therapy with a particular NSAID at the recommended dosage, another NSAID from another chemical class should be tried. The side effects of NSAIDs should be considered in patients who are elderly, have comorbid disease states (hypertension, diabetes, congestive heart failure, renal failure, peptic ulcer disease), or may be taking concurrent medications (e.g., diuretics) that may reduce renal blood flow. The primary adverse effect of NSAIDs is a tendency to cause bleeding and ulcerations in the stomach. A strategy to manage this condition is to prescribe misoprostol (Cytotec) concurrently for patients to take with their NSAIDs. Since misoprostol is a synthetic prostaglandin, it both prevents and heals NSAID-induced ulcers. A fixed combination product of diclofenac and misoprostol is available commercially. This product has been designed for patients who are at increased risk of developing gastric or duodenal ulcers from NSAID therapy. Patients receiving this fixed combination therapy had a reported gastric ulcer rate of 3%–4%, compared to 11% with diclofenac alone. Combination products of misoprostol and other NSAIDs are also being developed.

Corticosteroids: Corticosteroids have been proven to rapidly and effectively reduce inflammation and relieve symptoms in patients with rheumatoid arthritis. However, the development of adverse effects with corticosteroids, when taken for extended periods of time and at higher doses, limits their use. Intra-articular injections of steroids are generally safe and effective when administered appropriately, and can provide patients with immediate relief. Injections directly into the joint may also allow the patient to regain more range of motion in joints that have become stiff and inflamed. Low-dose oral corticosteroids (10 mg of prednisone daily or the equivalent) are beneficial for patients during the following situations: acute flares, special life events, the period of therapy after a DMARD has been initiated but not yet reached full effect, or when unacceptable discomfort or functional limitations persist despite full-dose NSAID and/or DMARD therapy.

The patient should be closely monitored for the development of side effects such as adrenal suppression, Cushing’s syndrome, osteoporosis, glaucoma, cataracts, gastritis, and hypertension. In patients receiving steroids for only 1–2 weeks, the corticosteroid need not be tapered since adrenal suppression is minimal over such a short period of time. However, in patients receiving doses of corticosteroids for greater than one month, tapering should occur gradually and be proportional to the length of time that the patient was on corticosteroids. Slow tapering of glucocorticoids allows the body to resume its natural production of cortisol, which becomes suppressed when patients take exogenous sources of steroid. It may be necessary to decrease the dose of corticosteroid by 1 mg every 1–2 weeks if the patient experiences symptoms of rheumatoid arthritis or has other complaints. A goal of any corticosteroid therapy should be to limit the use of the corticosteroid and avoid long-term therapy if possible.

Disease-Modifying Antirheumatic Drugs: Since active disease leads to irreversible joint and bone damage, it is important to start patients on DMARD therapy as soon as possible. Initiation of DMARD therapy is crucial in the management of rheumatoid arthritis. For a patient with a confirmed diagnosis, therapy should not be delayed beyond three months if, despite full-dose NSAID therapy, he or she has continued joint pain, significant morning stiffness or fatigue, active synovitis, or persistent elevation in ESR. The goal is to intervene before joints become damaged. While NSAIDs and corticosteroids alleviate symptoms, joint damage can still occur during their use, and the disease will progress. Disease-modifying agents such as hydroxychloroquine (HCQ), sulfasalazine (SSZ), methotrexate (MTX), gold salts, d-penicillamine (DP), and azathioprine (AZA) are intended to reduce or prevent joint damage, preserve joint integrity and function, maintain patient productivity and reduce total healthcare costs of patients with rheumatoid arthritis.

DMARDs as a class have a relatively slow onset of effect (1–6 months) and each patient will respond differently to various agents. Each DMARD also has its own unique toxicities which require close monitoring in order to avoid adverse events (Table 2). Patients must be educated about the potential risks versus benefits before initiating therapy.

The best initial DMARD for treatment of rheumatoid arthritis has not been established. SSZ or HCQ is usually selected for patients with mild disease. Both are available generically and have convenient dosing schedules and favorable safety profiles. HCQ therapy requires no additional laboratory monitoring, although patients should receive eye exams every 6–12 months to detect the development of reversible retinal toxicity (i.e., decreased night vision, loss of peripheral vision). SSZ requires that patients have routine CBCs to detect possible development of blood dyscrasias. The onset of action of these therapies should be apparent within 1–6 months; if no response is seen after this time, a change in therapy is warranted.

Methotrexate is the drug of choice in patients who have a more severe form of the disease (for example, erosions or extra-articular manifestations). Low-dose, once-weekly therapy has become a mainstay of treatment because MTX is relatively inexpensive; the cost of monitoring for toxicity is less than that of monitoring with use of gold, penicillamine or immunosuppressive agents; and there is a high rate of clinical response. The onset of action is generally within several weeks of initiating therapy, and patients are likely to still be on treatment after 5 years. Other DMARDs do not have such a quick onset of effect or long-term patient tolerability.

Methotrexate therapy is usually initiated at 7.5 mg/week. This dosage may be either increased or decreased depending on efficacy or development of toxicity. The usual dose is from 7.5–15 mg/week. To aid patients in appropriately taking MTX therapy, specially designed dose packs are available. Each dose pack contains one month’s worth of MTX therapy. The tablets are grouped by weekly doses and clearly marked to improve patient adherence. All of the dose packs contain 2.5 mg MTX tablets but are available in different weekly doses.
Prior to beginning MTX therapy, it is necessary to perform baseline laboratory work. A CBC with differential, platelet count, liver function tests, hepatitis B and C studies, serum creatinine and chest x-ray should be obtained. Subsequently, every 1–2 months CBC with platelet count, AST, and albumin should be evaluated. These tests, along with routine chest x-rays, help to monitor for thrombocytopenia, leukopenia, anemia, renal insufficiency, liver fibrosis, and pulmonary changes that are associated with MTX therapy. Side effects such as nausea, vomiting, diarrhea, and stomatitis may develop. These side effects may be minimized with the administration of folic acid 1 mg/day. Concurrent administration of folic acid decreases the incidence of side effects by 50% without decreasing the clinical efficacy of MTX.20 It is also possible to split the MTX dose over 24 hours instead of taking all of the tablets at once, or administer MTX subcutaneously or intramuscularly should GI discomfort continue.

Contraindications and drug interactions are also considerations when initiating MTX therapy. Since it is highly teratogenic, MTX should not be given to pregnant or lactating females. Patients who are known alcoholics or have alcohol-associated liver disease should not receive MTX since hepatic fibrosis may develop. Methotrexate should also not be used in patients who are immunocompromised, are known to be nonadherent with therapy, or have existing blood dyscrasias. Patients should be educated to avoid excessive alcohol intake since it may contribute to the development of liver toxicity. Other drugs to be avoided include phenytoin (alters protein binding), trimethoprim/sulfamethoxazole (has anti-folate activity), aminoglycosides (is nephrotoxic) and probenecid (is nephrotoxic). Concurrent administration of any of these medications significantly increases the risk of developing toxicity.
Gold and penicillamine have been used for many years in the treatment of rheumatoid arthritis. Although neither agent is used frequently anymore, they may be utilized in refractory cases of rheumatoid arthritis. While patients respond successfully to gold therapy, many have to discontinue therapy within 1 year due to development of toxicity (anemia, leukopenia, thrombocytopenia, proteinuria) or decrease in efficacy. Penicillamine is comparable to gold in efficacy; however, side effects (nausea, vomiting, diarrhea, hypogeusia) limit its clinical use. A word of caution when using penicillamine is that 10% of patients who have an allergic reaction to penicillin will have a hypersensitivity to penicillamine; however, this is not an absolute contraindication to therapy

Immunosuppressive Agents: In addition to MTX, cyclophosphamide, cyclosporin A and AZA are immunosuppressive agents used to manage rheumatoid arthritis. These therapies are generally reserved for severe cases unresponsive to other treatments. These agents are effective in controlling the symptoms of rheumatoid arthritis but have the same toxicities associated with any chemotherapeutic agent. Side effects such as myelosuppression, hepatotoxicity, GI disturbances, and hemorrhagic cystitis are commonly seen with cyclophosphamide, cyclosporin A and AZA. Cyclosporin A has proven beneficial in patients who fail to respond to DMARD therapy but is more toxic than DMARDs. Women should be informed of the fetal risk associated with the agent being used, and appropriate measures should be taken to ensure effective contraception.

Management Rheumatoid arthritis

Both nonpharmacological and pharmacological modalities should be utilized to manage rheumatoid arthritis, including surgery, if indicated. Although there is presently no cure for rheumatoid arthritis, the goals of therapy are to control disease activity; alleviate pain; maintain function for essential activities of daily living and work; maximize quality of life; slow the rate of joint damage; and, if possible, induce complete remission.

Nonpharmacologic: Nonpharmacologic therapy is an important component of managing rheumatoid arthritis. These modalities help patients to manage their own disease and maintain their quality of life. Patient and family education should focus on the pathology and course of the disease; options for drug and nondrug therapy; potential drug interactions and side effects; and monitoring the progression of the disease. Physical therapy is important to preserve and maintain range of motion of joints and prevent muscle atrophy. Adequate rest will help decrease systemic inflammatory responses, protect the joints, and permit repair. The key is to maintain balance between proper rest and physical activity. To minimize joint instability and maintain strength, individualized exercise programs should be designed to move joints through their full range of motion. Occupational therapy teaches patients how to manage activities of daily living (ADLs) and properly use supportive devices such as canes or splints, which may become necessary as the disease advances. Support services such as the Arthritis Foundation and local patient support groups can significantly benefit patients and their families.

Pharmacologic: Agents available to manage rheumatoid arthritis continue to increase in number. Historically, the pharmacologic approach to managing rheumatoid arthritis was represented as a pyramid. Therapy was initiated with salicylates or nonsteroidal anti-inflammatory drugs (NSAIDs). When this therapy was no longer effective in providing symptom control, patients would move to the next level — disease-modifying anti-rheumatic drugs (DMARDs). DMARDs may help to slow progression of the disease or induce remission. If DMARDs do not achieve desired results or the patient develops toxicity, options are limited and patients often are placed on combination therapy or experimental protocols.
The pyramid was designed to start patients on what was believed to be the least toxic medication during the early stages of the disease. As the disease progressed, more toxic medications were used. While NSAIDs are at the bottom of the pyramid, such side effects as GI ulcerations and changes in kidney function can be problematic, especially in the elderly. It has been recently recognized that joint and bone erosion can develop after only a couple of months of experiencing rheumatoid arthritis symptoms; therefore, the pyramid approach has been largely abandoned in favor of more aggressive therapy given early in the disease.
Wilske and Healey proposed a “step-down bridge” alternative to the pyramid for the treatment of rheumatoid arthritis. They suggested that combinations of drugs given early in the disease may induce remission and prevent joint destruction. Patients were started with a fast-acting anti-inflammatory (corticosteroid). If symptoms persisted after one month, a DMARD was added to the regimen. After three months, the patient was tapered off the steroid and continued on the DMARD. In order to control acute flare-ups, patients were given methotrexate and, as needed, steroids. A variation on this treatment strategy, the “sawtooth approach,” utilizes combinations of DMARDs and substitutes new agents if benefit from the original agents is lost. Patients are then gradually tapered off the various medications, leaving them on a single DMARD. Critics of the “step-down bridge” approach state that it unnecessarily exposes patients to toxic medications. Since it is not possible to determine which patients will develop aggressive disease, exposing all patients to combination therapy adds additional costs for drugs and monitoring. The risk–benefit ratio for combination therapy is still being evaluated. Some patients displaying less than optimal response may benefit from the use of combinations of DMARDs.

Over-the-counter (OTC) salicylates and NSAIDs include aspirin, ibuprofen, magnesium salicylate, naproxen, and ketoprofen (Table 1). The anti-inflammatory response desired in rheumatoid arthritis is achieved at higher doses than those recommended on the OTC product labeling.

Rheumatoid arthritis (RA) is an autoimmune disorder of unknown etiology in which the synovium, or joint lining, is attacked by the immune system; the resulting inflammation leads to destruction of the synovium and surrounding joint. A chronic disease, rheumatoid arthritis requires early diagnosis and aggressive treatment in order to minimize the morbidity associated with its advancement. Rheumatoid arthritis affects 1% of the population — approximately 2.5 million Americans. Most patients diagnosed are between the ages of 35–50; however, about 20% of patients are diagnosed with rheumatoid arthritis after the age of 60, with an overall prevalence of disease in the over-60 population of 2%–3%. Women are three times more likely than men to develop rheumatoid arthritis and typically experience a more severe and debilitating form of the disease. There appears to be a genetic tendency in developing rheumatoid arthritis since first-degree relatives of patients seropositive for rheumatoid factor have a three- to four-fold increased risk of developing rheumatoid arthritis themselves.

Rheumatoid arthritis mainly affects the small joints of the hands, wrists, and feet, although larger joints such as hips, knees, and shoulders, may also be involved. Joint swelling, erythema, stiffness, warmth, and pain are classic symptoms of early disease. As rheumatoid arthritis progresses, joint deformities such as subluxation of the wrists, swan-neck and Boutonniиre deformities of the fingers develop, resulting in permanent disfiguration and disability. Patients may also develop extra-articular manifestations, such as soft tissue nodules, pericarditis, neuropathies, muscle atrophy, and fatigue.

Rheumatoid arthritis is associated with several clinical laboratory abnormalities. Normochromic, normocytic anemia (anemia of chronic disease) is present in about half of patients. The erythrocyte sedimentation rate (ESR) is elevated in 85%–95% of patients due to the inflammatory component of rheumatoid arthritis. ESR is not diagnostic for rheumatoid arthritis, and the results should be interpreted carefully since this value may increase with normal aging, infection, or inflammatory conditions. Aspirate of the synovial fluid from affected joints will show increased numbers of white blood cells and is often turbid in appearance, another indication of inflammation. Rheumatoid factor is present in 60%–70% of patients with rheumatoid arthritis. While the test is not specific for rheumatoid arthritis, it does provide a marker to gauge the severity of disease. By performing serial dilutions, one can determine the concentration of rheumatoid factor. Higher dilutional titers usually indicate more severe disease. Patients may also have elevated C-reactive protein (CRP) and decreased serum albumin.
Rheumatoid arthritis is a difficult disease to manage due to the waxing and waning nature of the symptoms, and prognosis is directly related to onset of disease. Approximately 80% of rheumatoid arthritis patients experience a cyclical pattern, in which periods of remission lasting up to a year are followed by disease flares. About 10% of patients will have one acute episode of arthritis and then enter a spontaneous permanent remission. Another 10% have a severe, debilitating form of the disease that leads to severe bone erosion and joint deformity. Patients with a rapid, sudden onset are more likely to have remission within the first year. A more gradual onset, over 6 months, is indicative of a persistent disease that may not remit. Poor prognostic indicators include high levels of rheumatoid factor, extra-articular manifestations, diagnosis at younger than 30 years of age, and female gender.

Should people consider joint surgery?

The decision to have surgery is a major one. It is not a decision to be made quickly without good reasons. Most people with arthritis never will need surgery. Their arthritis is managed by non-surgical treatments, including proper medication, physical therapy, exercise, rest and joint protection. A person unsure about surgery should ask their doctor to suggest a consulting physician and get a second opinion.

Benefits of joint surgery

Joint surgery offers several potential benefits for some people with arthritis. Relief of pain is the most reliable benefit and therefore is the major reason for surgery for people with arthritis. For some, joint surgery also may offer better movement and ability to use joints. Another benefit is an improvement in the look of deformed joints, especially joints in the hand. It is most important to consult with a doctor about which benefits are likely to be obtained from joint surgery.

Reasons not to have joint surgery

Before any kind of surgery, it’s important to have other health problems under control. If there are any problems with the lungs, a serious heart disease, a bacterial infection or other health problems such as diabetes, some types of surgery may be too much. Being overweight also can cause complications, especially if the surgery is on a weight-bearing joint such as a hip or knee. Age also is a factor when considering surgery. Despite significant advances in joint surgery, the younger a person is at the time of the surgery, the more likely it is that the surgery will have to be repeated later. This is because artificial joints tend to loosen with time, and younger people tend to be more active, therefore placing more stress on surgically-treated joints.

Which joints can benefit; what types of surgery are available?

Joints that can benefit from surgery are joints in the foot and toes, ankle, knees, hips, hand and fingers, wrist, shoulder. Among the types of surgery available are arthrodesis or bone fusion, arthroplasty or the rebuilding of joints, osteotomy or the correction of deformity by cutting and then resetting the bone, resection or removal of a bone or bone part, synovectomy or removal of the diseased synovium that surrounds the joint area.

What to expect after surgery

Depending on the type of surgery, a period of rest, physical therapy and limited activity will be prescribed. Also, there may be a need to use splints, a cane or crutches. Physical therapy is vital to restore range-of-motion in the joint and strengthen muscles. The pain associated with the therapy will gradually lessen.

What problems are faced by people who have arthritis?

Most forms of arthritis are chronic, meaning they can last a lifetime, and people often feel a sense of shock, disbelief or helplessness when they are diagnosed with the disease. Arthritis brings both physical and psychological effects. The pain and limited movement can make ordinary daily tasks nearly impossible. Simply getting out of bed, dressing, bathing, walking, or opening doors can all become major chores. Psychologically, the daily pain can lead to increased stress and fatigue. This pain, stress and fatigue can lead to anger and depression. There are also strains on the interrelationships between the person with arthritis and family or friends.

How can people with arthritis take charge of their lives?

It is very important that people with arthritis feel in control of their condition rather than feel controlled by their condition. There are a number of techniques that can be used to take charge of arthritis including:

• learning as much as possible about arthritis
• becoming an active partner in the treatment of arthritis by asking questions and following an individual health care plan
• finding new ways to cope with physical limitations
• asking for help when it is needed
• sharing frustrations and successes with family and friends
• using open, honest communication in personal relationships
• setting realistic, flexible goals for achievements in life

How can people cope with the pain caused by arthritis?

Pain is the one constant for all forms of arthritis. It can be severe and life long. People with arthritis need to recognize pain as a warning signal and take appropriate steps to manage it. Pain management is one of the prime goals of an arthritis treatment plan. This plan may include medications, rest, a therapeutic exercise program, joint protection techniques and the application of heat and cold.

How can people with arthritis resolve the stress and fatigue caused by their condition?

Stress and fatigue can be part of the negative cycle of arthritis. There are a number of techniques people can use to combat stress and fatigue including:

regular exercise

use of relaxation techniques

learning to say “no” without feeling guilty

balancing rest and activity

planning ahead to make work easier

maintaining proper body posture and practice joint protection techniques

getting enough sleep

What Are Unproven Arthritis Remedies?

Unproven arthritis remedies are treatments that have not shown in repeated scientific studies that they work and are safe. Proven treatments for arthritis must show in repeated, controlled scientific tests that they work by meeting one or more of the following goals:

• reduce pain
• reduce inflammation
• keep joints moving safely
• avoid stress damage to joints

Proven treatments also must show how safe they are. The benefits of a treatment in controlling arthritis should be greater than the risk of unwanted or harmful effects. Some unproven remedies are harmless. Others are harmful. Still others have health effects that are unknown. Even if an unproven remedy is itself harmless, it can still have a detrimental effect if it causes a person to stop or slow down proven treatments to control arthritis. Listed below are some examples of unproven remedies.

Harmless:

copper bracelets

mineral springs

uranium mines

vibrators

vinegar and honey

Harmful:

DMSO (Dimethyl sulfoxide)

large doses of vitamins

drugs with hidden ingredients such as steroids

snake venom

Unknown:

biofeedback

diets

fish oil

lasers

yucca

Why Do People With Arthritis Try Unproven Remedies?

Arthritis is painful, potentially crippling and usually chronic. Treatments vary for each type of arthritis and among different individuals. Doctors may have to try many different approaches before finding a combination that works for a particular individual. And even when a successful treatment program is discovered, it may need to change over time as the disease changes. Many people with arthritis become discouraged with this process and hope for a quick and easy answer.

Arthritis symptoms may come and go without warning. A person using an unproven remedy may mistakenly think the remedy worked simply because they tried it when symptoms were going into a natural remission.

People with arthritis may seem to improve because of the placebo effect. The power of positive thinking may cause someone to temporarily feel better. The improvement usually lasts only a short time, and the underlying disease continues to cause damage.

Cost Of Unproven Remedies

The Arthritis Foundation estimates that most people with arthritis have tried an unproven arthritis remedy at some point.

One in ten people who have tried unproven arthritis remedies report harmful side effects, according to a Health and Human Services survey.

An estimated $1 billion is spent yearly on unproven arthritis remedies.

Any unproven remedy, no matter how harmless, can become harmful if it stops or delays someone from seeking a prescribed treatment program from a physician.

How Can People Determine If A Remedy Is Unproven?

It may be hard to spot an unproven remedy at first glance. The only source of information about a remedy may be what is given out by its promoters. People with arthritis should be cautious if the proposed remedy falls into one or more of the following categories:

A. Works for all types of arthritis
There are over 100 types of arthritis and treatments vary for each kind.

B. Uses case histories and testimonials
Claims of individuals helped by a treatment need to be backed up by repeated studies on large numbers of people.

C. Cites only one study
A single study may get results which other studies cannot repeat. A number of scientists must repeat the same study and get similar results for a treatment to be considered proven. A single study may, however, suggest a treatment that may have promise and should be studied further.

D. Cites a study without a control group
The use of a control group helps show that the results are due to the new treatment and not to some other factor.

E. Does not list contents
Some ads for a miracle drug for arthritis actually are just aspirin at a high price. Other treatments have been found to contain corticosteriods and other powerful drugs. These drugs may have severe side effects and should not be taken without a doctor’s supervision.

F. Has no warnings about side effects
There should be warnings on the label or instructions stating who should not use the treatment.

G. Claims to be based on a secret formula
Scientists share their discoveries so that other experts in arthritis can review and question their findings.

A balanced diet and careful weight control can help people with arthritis manage the pain, inflammation and loss of movement caused by arthritis. Experts in diet recommend seven basic guidelines for a balanced, healthy diet:

• Eat a variety of foods;
• Maintain ideal weight;
• Use fat and cholesterol in moderation;
• Use sugar in moderation;
• Eat plenty of vegetables, fruits and grain products;
• Use salt and sodium in moderation;
• If you drink alcohol, do so in moderation.

  What are some diet problems people with arthritis may face?

  Fatigue and pain can lower appetite. Swollen joints and loss of movement may lead people with arthritis to avoid foods, such as vegetables, that need more time or effort to prepare and cook. Some kinds of arthritis, and some medications, can affect the body’s ability to use food.

  What about weight?

  Weight control is an important concern for people with arthritis. Keeping close to your ideal weight helps decrease the pressure on the knees and hips, which bear much of the weight of the body. In a study funded in part by the Arthritis Foundation (published in the April 1, 1992, issue of the Annals of Internal Medicine), researchers found for the first time that overweight, middle-aged and older women can significantly lower their risk for developing osteoarthritis of the knee by losing weight. For people with arthritis, it is important to keep trim by reducing fats, cholesterol and sugar in their diets.

  What has research shown about diet and arthritis?

  In addition to the benefits of a good diet, research has shown several other connections between food and some forms of arthritis or arthritis-related conditions. These include links with gout, osteoporosis (an arthritis-related condition in some situations) and Reiter’s Syndrome. For instance, people with gout have difficulty with the way they use or get rid of chemicals called purines. Researchers now think that diet may serve as a risk factor by increasing the chances for developing certain kinds of arthritis. Diet may change the way the immune system reacts in certain kinds of arthritis that involve inflammation. Researchers also are investigating the effects of food allergies and reactions; fasting, low calorie or low fat diets; and fatty acids such as fish oils on rheumatoid arthritis.

  What about those special diet claims?

  Researchers only accept that there is a connection between diet and arthritis after a number of studies show the same results. However, some people claim that special diets, foods or supplements can cause or cure arthritis. The claims usually appear in magazine articles, books and on talk shows. Most claims for such diets have not been scientifically tested to prove that they work and are safe. In fact, some claims for special diets for arthritis are health frauds. There is no scientific basis for most of these claims. Other diet claims are still under study. When you hear about diet claims in the treatment of arthritis, ask the following questions:

• Does the diet eliminate any group of foods?
• Does it stress only a few foods or eliminate others?If the answer is yes to either question, it is probably an unproven diet.

  How do I find out more?

• Check with a doctor for ways to manage weight and to discuss specific diet options.
• Request the Arthritis Foundation Diet and Your Arthritis brochure.The information provided by the Arthritis Foundation should not take the place of advice and guidance from your own health-care providers. Be sure to check with your doctor about changes in your treatment plan.

Answer true or false to the following questions:

1. Vitamin D helps protect against osteoarthritis.

2. The best way to control joint pain is to stay off your feet as much as possible.

3. Eating low-fat foods can keep joints healthier.

4. Swallowing gold is a medically sound treatment for arthritis.

5. The only way to cure arthritis is to use the proper combination of medications.

Answers

1. True. Recent research from the ongoing Framingham Heart Study, (which has followed participants for more than 40 years), revealed that people with very low vitamin D intake and low blood levels of vitamin D were three times more likely to experience progressively worse osteoarthritis knee pain than those with high levels of vitamin D intake. But taking separate vitamin D supplements is not recommended because too much can be harmful. The best sources are sunlight (from which the body manufactures its own vitamin D), liver, salmon, fortified milk and butter, and egg yolks.

2. False. The Arthritis Foundation recommends low impact, weight-bearing exercise-such as walking and gardening-to help control joint pain and inflammation. Another way to gain the same benefits is to run in place, or swim in a heated pool.

3. True. Dietary fat contributes to osteoarthritis because excess weight subjects joints to extra wear and tear, causing inflammation, pain, and stiffness.

4. True. Oral gold (auranofin) is sometimes prescribed to slow the progression and relieve the symptoms of rheumatoid arthritis (But it is not used for arthritis.) The auranofin drug, Ridaura, can take several months to be effective, and those taking it must be monitored closely.

5. False. There’s no cure for most forms of arthritis. But treatment can reduce pain, and medications are used most often for this purpose. Other important therapies include losing weight, guarding against overuse of joints, and resting during flare-ups. Surgery can return mobility to some people with severe arthritis.

Arthritis

Take steps to banish the pain of osteoarthritis and live life to the fullest.

Osteoarthritis — a degenerative disease caused by the gradual breakdown of the cartilage that cushions the tips of the bones — affects almost 16 million Americans, most of them over the age of 45.

Osteoarthritis, or OA, usually strikes weight-bearing joints such as the knees and hips, but can also affect the elbows, fingers, neck, spine, and wrists. Joints that have suffered previous injuries or infection appear to be the most vulnerable to the disease, but the simple wear and tear of aging can also aggravate the condition. In fact, half the population over the age of 60 has symptoms of osteoarthritis, while another 10 percent to 20 percent show signs of it on X rays.

Osteoarthritis, which is marked by a degeneration of the cartilage that lines joints and by bony outgrowths, can occur after a joint injury or as a result of joint deformity. The simple wear and tear of aging tends to aggravate the condition. And new research suggests that an imbalance in the enzymes and hormones that normally repair and maintain joints also plays an important role.

Symptoms can be subtle and easily overlooked until one day your fingers may feel too stiff to open a jar, or your hip joint aches so much that it’s uncomfortable to get out of a chair. In addition to stiffness and achiness, other common signs include difficulty reaching or bending and a grating noise as bones rub together.

Though most people first notice the disease in their fingers and knees, osteoarthritis-which tends to run in the family-can affect any joint, including those of the feet, hips, and back. If you’re experiencing joint pain, stiffness, or crookedness, see your family doctor, internist, or an arthritis specialist (rheumatologist) to first find out whether you have the disease. Although there is no cure for OA, there is a lot you can do to fight its effects.

Coping With Pain

In the past, non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, and naproxen, were the first choice of treatment for OA pain. Now, the American College of Rheumatology suggests acetaminophen (Tylenol and others) in doses of up to 1,000 mg four times a day-especially for OA of the knee or hip-as a first line of defense. The reason: Long-term NSAID use may irritate the stomach lining.

But if acetaminophen doesn’t ease pain, an over-the-counter (OTC) NSAID can be the next step. If that doesn’t help, your doctor will most likely prescribe a more potent NSAID, sometimes in combination with a second prescription agent, called Cytotec (to prevent stomach problems).

If your arthritis resists even prescription NSAIDs, doctors may prescribe corticosteroids injected into tissues and joints. These drugs are used sparingly because chronic use can have destructive effects on bones and cartilage.

Two other pain-relief options have recently become available. The first, Synvisc, is a cushioning fluid approved for use in knees (though it may prove beneficial for other joints as well). The drug is injected by a doctor directly into the knee joint. The second new treatment is Hyalgan (sodium hyaluronate), an injectable version of a chemical normally present in high amounts in joints and fluids. In OA sufferers, the quality and quantity of hyaluronate may be poor.

Topical Pain Relievers

Applying heat — via a heat lamp, hot water bottle, heating pad, or moist steam pack — can help relax the muscle tension created by sore and rigid joints. Cold packs can numb sore areas temporarily and ease inflammation and swelling. Massaging the skin over the joints can also reduce discomfort.

Another option is an OTC topical painkiller, available in creams, rubs, or sprays. Most contain counter-irritants, substances that make the skin feel hot, cold, or itchy. Common counter-irritants include camphor, capsaicin, menthol, and salicylates (similar to aspirin).

To use, rub the directed amount into the sore area, avoiding contact with wounds or sores, as well as eyes, mouth, and other mucous membranes. Don’t use counter-irritants more frequently than the directions suggest. Make sure you wear gloves while applying them or wash your hands immediately after use. (If you’re treating hand pain, wait 30 minutes before washing.)

Smart Lifestyle Strategies

Your family doctor, rheumatologist, physical therapist, or a local chapter of the Arthritis Foundation can help you develop a plan that may prevent or slow the progression of OA. Strategies are likely to include: Gentle exercise to put joints through their range of motion every day. Stretches to maintain muscle length. This helps keep joints moving properly. A light weight-lifting routine daily to prevent muscles from weakening. Avoiding injury and overuse. Shedding excess weight.

Caution: If you have a history of gastrointestinal disease, alcohol abuse, or regularly consume more than three alcoholic drinks per day, consult your doctor before beginning acetaminophen or NSAID treatment. Regular NSAID use increases the chances of stomach bleeding, a risk that rises even more if you smoke, drink alcohol, take corticosteroids, or have had an ulcer.

Tell your doctor if you have ever had any unusual or allergic reactions to NSAIDs, or if you are allergic to any other substances such as food, preservatives, or dyes. Notify your doctor if you experience a burning sensation in the stomach while taking NSAIDs.

Avoid topical products that contain salicylates if you are sensitive to aspirin. Use them with caution if you have asthma or nasal polyps. Don’t use a heating pad with a counter-irritant; it can lead to a skin burn.

What Are Glucosamine and Chondroitin?

You may have heard that taking glucosamine sulfate and chondroitin sulfate can halt and even reverse osteoarthritis, without side effects. Both are natural substances in the body that help form cartilage. Glucosamine and chondroitin stimulate cartilage growth; chondroitin also prevents its breakdown.But are they effective as supplements? According to the Arthritis Foundation, several small studies have reported beneficial effects with glucosamine and chondroitin, separately. So have many animal studies. In fact, veterinarians use glucosamine to treat animals with arthritis. Large, controlled studies however — the gold standards for scientific research — have yet to be completed. So for now, neither the American College of Rheumatology nor the Arthritis Foundation recommend glucosamine or chondroitin. And the FDA has not approved them to treat arthritis. If you want to try these products, it’s a good idea to talk with your doctor first.

Possible Drug Interactions Drugs or foods that may interact with, decrease, or increase the effects of the medication you’re taking: Non-steroidal anti-inflammatory drugs (NSAIDs) may interact with antipsychotic medications; anti-seizure medications; beta blockers; blood thinners; gout drugs; heart medications; high blood pressure drugs; other NSAIDs; and sulfa drugs. Talk with your doctor before taking salicylate-containing (aspirin-like) products if you are taking blood thinners such as warfarin (Coumadin).