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Rheumatoid Arthritis – Treatment

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 Rheumatoid Arthritis

Rheumatoid arthritis is a chronic disease, which is affecting peripheral joints. Given that rheumatoid arthritis is an inflammatory disease, in which the pathogenic immune process causes cartilage destruction and bone erosion, the treatment of rheumatoid arthritis has the following objectives:

  1. Fighting the articular and extra-articular inflammatory process of rheumatoid arthritis.
  2. Interfering with the pathogenic chain of rheumatoid arthritis by using disease modyfing anti-rehumatic drugs (DMARDs).
  3. Maintain or restore the  morphological and functional integrity of the joints.                                                                                                                                                                                                                                                                    
    Fighting the articular and extra-articular inflammatory process, in rheumatoid arthritis using anti-inflammatory medications (non-steroidal and steroidal).

Rehumatoid Arthritis

Non-steroidal anti-inflammatory drugs (NSAIDs):

Considering the selectivity for the inducible cyclooxygenase (COX2), NSAIDs used to treat rheumatoid arthritis are:

  • Classic NSAIDs:  inhibit COX1 and COX2 approximately equal (aspirin, diclofenac, ketoprofen, tenoxicam, indomethacin, ibuprofen);
  • COX2 – selective: predominantly inhibit COX2 compared to COX1, which causes high antiinflammatory activity and few adverse effects (meloxicam, nimesuluid);
  • COX2 – specific: only inhibit COX2. They have an antiinflammatory efficiency comparable to diclofenac in optimal dose, but with fewer side effects (celcoxib, etoricoxib).

Adverse effects of NSAIDs are upper gastrointestinal bleeding, gastroesophageal reflux, anal heartburn (especially if using suppositories), mucocutaneous manifestations (rash, itching, bronchospasm, allergic rhinitis).

In usual doses, therapeutic response to NSAIDs is individualized, meaning that the same drug have varied effects from case to case.

Corticosteroid therapy:

Corticosteroid therapy is used in rheumatoid arthritis, in situations where inflammation is not controlled by NSAIDs. There are three ways of administering cortisone preparations:

Oral use (prednisone). In severe cases of rheumatoid arthritis (acute multiple arthritis, pyrexia, profound alteration of general condition): prednisone in doses of 60-80 mg / day or 1 mg / kg / day or 30-40 mg / day for 1 – 2 weeks. The dose is reduced by 5 mg per week, and when it comes to doses of 15-20 mg / day, is switched to alternate administration (eg., one day is administered 15 mg of prednisone and the next day 5 mg of prednisone or pause) . The total duration of treatment is 3-4 weeks or months.

In medium forms of rheumatoid arthritis, it is recommended taking prednisone at a dose of 5-7.5 mg / day for a long time (months). This is active management is minimizing the adverse effects of corticosteroid therapy.

Intravenous administration of methylprednisolone is an indication in an exacerbation of rheumatoid arthritis. Is recommended pulse therapy and consists in daily administration, in intravenous infusion, of 1 g of methylprednisolone in 200 ml of NaCl 9° or glucose 5% for 3 days, consecutive. Antiinflammatory effects occurs rapidly and lasts 30-40 days. Efficiently is the mini-pulse therapy, consisting of 100-200 mg of methylprednisolone administration by intravenous infusion for 3 consecutive days, especially recommended in situations of rebound occurred during the reduction of prednisone dose.

Administration of intra-articular corticosteroids is recommended when the inflammatory process persists at 1 or 2 joints. Is recommended a maximum of 3-5 injections.

Methylprednisolon

Methylprednisolon

Disease modyfing anti-rehumatic drugs (DMARDs):

Methotrexate (2.5 mg tablets), a folic acid antagonist, has become the most widely used DMARDs agent because it has a not very late onset, after 4-6 weeks, ease of administration and good tolerance. Therapy with methotrexate is indicated for patients with active form of rheumatoid arthritis and poor prognosis, and the dose ranges from 7.5-25 mg / week in three doses at intervales of 12 hours. Stomatitis, alopecia and mild abdominal discomfort, arising from the antagonism of folic acid and can be improved by supplementation with folic acid (1mg/day). Fortunately, most serious complications of methotrexate therapy (liver cirrhosis, pulmonary fibrosis, severe mileosuppression) are rare. Routine monitoring of toxicity is mandatory and includes complete blood count, weekly and then monthly, dosage of AST, ALT, serum albumin and serum creatinine at intervals of 4-8 weeks. Duration of treatment depends on results and side effects emerged, but anyway, is extended to several months or years.

Methotrexate

Methotrexate

Sulphasalazine (500 mg tablets) in doses of 2-3 g, is the first DMARDs used in patients with mild rheumatoid arthritis and negative rheumatoid factor. Although it is well tolerated, at only a limited number of patients with rheumatoid arthritis induces complete remission. Duration of therapy is similar to that of methotrexate.

Gold salts (Tauredon, ampoules of 10 mg and 50 mg), intramuscular injections are used in rheumatoid arthritis as follows: 10 mg in the first week, 20 mg in the second week and then 50 mg / week until the achievement of a therapeutic response or up to a total dose of 1 g. The treatment may prolong until the total dose of 2500-3000 mg.

Leflunomide (Arava tablets 10 mg, 20 mg and 100 mg) became available as an DMARDs agent in rheumatoid arthritis from 1998, is a effective imunosupersor similar to methotrexate, representing an alternative for unresponsive patients with rheumatoid arthritis at therapy with methotrexate or patients with methotrexate intolerance. The action of this drug is installed after 4-8 weeks. To achieve an optimal therapeutic concentrations is required a loading dose of 100 mg / day for 3 consecutive days, followed by a maintenance dose of 20 mg / day. Therapy monitoring is done by determining of complete blood cell counts and transaminases, every 2 weeks during the first month and then monthly.

Leflunomide

Leflunomide

Inhibitors of tumor necrosis factor alpha used in rheumatoid arthritis are :

  • Etanercept (Enbrel), a protein similar to a human monoclonal antibody that binds tumor necrosis factor alpha and inhibit its activity. It is available in ampoules of 25 mg and is injected subcutaneously 2 times a week. Therapeutic effect will appear after 1-2 weeks of treatment.
  • Infliximab (Remicade) is a genetically engineered monoclonal antibody that binds with high affinity and specificity the tumor necrosis factor alpha and inhibits it. In combination with methotrexate, inhibits the progression of disease in patients with moderate or severe rheumatoid arthritis who have inadequate or no response to methotrexate therapy. The first dose is 3 mg / kg, administered intravenously, followed by a dose of 3 mg / kg after 2 or 6 weeks after the first dose, then intravenous infusion every 8 weeks in combination with oral methotrexate for at least 1 year or as long as the disease is active.

Other chemotherapy medication use in rheumatoid arthritis: azathioprine, phosphamide, cyclosporin A, in normal doses are used for patients with aggressive forms of rheumatoid arthritis or forms of rheumatoid arthritis with extra-articular manifestations such as systemic vasculitis.

Infliximab

Infliximab

Maintain or restore the  morphological and functional integrity of the joints:

Synovial destruction, chemical with morurat or isotopic with lithium salts, by intra-articular injections, have very limited indications (one joint which is rebellious to medication).

Surgical procedures in rheumatoid arthritis can be practiced early in the disease or in advanced forms of disease.

When a few joints are interested with major synovial proliferation, synovial destruction is recommended, the procedure will improve the local and general condition. Splenectomy is recommended in rheumatoid arthritis associated with splenomegaly (Felty’s syndrome). In very advanced stages of rheumatoid arthritis, when there are major joint damage, orthopedic surgery can correct them by prostheses use.

In rheumatoid arthritis defined by clinical criteria of American College of Rehumatology, treatment is differentiated according to clinical form and stage of the disease. Obtaining a favorable response to one drug requires to continue the therapy, while inadequate response require the addition of other drugs.