Sulfasalazine Methotrexate

The most recent treatment paradigm calls for earher, more aggressive treatment of rheumatoid arthritis. DMARDs are frequently employed along with NSAIDs in the initial treatment of the disease. The COX-2 inhibitors are often used because they are less likely to cause serious GI toxicity than are the nonspecihc COX inhibitors. The usual DMARD of choice for patients with mild rheumatoid arthritis is hydroxychloroquine or sulfasalazine methotrexate is used for those with moderate to serious disease. Other DMARDs are used if these agents are poorly tolerated or do not produce suf-hcient response. Combination therapy of methotrexate and another agent is also used to treat disease that is not responsive to individual DMARDs. 

Azathioprine, chloramphenicol, colchicine, cyclophosphamide, cytarabine, 5-fluorodeoxyuridine, 5-fluorouracil, hydroxyurea, mercaptopurine, metformin, methotrexate, phenobarbital, phenytoin, primidone, proton pump inhibitors, pyrimethamine, sulfasalazine, and vinblastine... 

In addition to relying on safety and efficacy data, the initial DMARD choice depends on disease severity, patient characteristics (i.e., comorbidities, likelihood of adherence), cost, and clinician experience with the medication.1,7 Methotrexate alone or in combination therapy is the initial treatment of choice for patients with aggressive disease. Patients with early, mild disease may receive monotherapy with sulfasalazine or hydroxychloroquine. Agents such as azathioprine, D-penicillamine, and gold salts are used rarely today because of concerns about toxicity and reduced efficacy.1,15... 

Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.17 29 Oral agents include sulfasalazine, acitretin, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the biologic response modifiers alefacept, efalizumab, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis. 

Sulfasalazine is an antiinflammatory agent that inhibits 5-lipoxygenase. It is used selectively as an alternative treatment, particularly in patients with concurrent psoriatic arthritis. When used alone, it is not as effective as methotrexate, PUVA, or acitretin. However, it has a relatively high margin of safety. The usual oral dose is 3 to 4 g/day for 8 weeks. Its adverse effects are similar to other sulfonamide antibiotics. 

In the majority of patients, active Crohn s disease is treated with sulfasalazine, mesalamine derivatives, or steroids, although azathioprine, mercap-topurine, methotrexate, infliximab, and metronidazole are frequently used. 

Keywords Azathioprine methotrexate pharmacogenetics polymorphisms rhen-matoid arthritis sulfasalazine tumor necrosis factor antagonists. 

This chapter highlights some of the recent major pubhcations in the field of pharmacogenomics in RA and describes the implications of this field for future research and cUnical care. The pharmacogenetics of three major DMARDs (methotrexate [MTX], azathioprine [AZA], and sulfasalazine [SSZ]) and one class of biologic DMARDs, the tumor necrosis factor (TNF) antagonists, in RA, are reviewed. 

For rheumatoid arthritis, the pharmacogenomics of three major diseasemodifying antirhenmatic drags (methotrexate, azathioprine, and sulfasalazine) and one class of biologic antirhenmatic drags (the tumor necrosis factor antagonists) are discnssed in detail. 

Drugs that may interact with folic acid include aminosalicylic acid, oral contraceptives, dihydrofolate reductase inhibitors (eg, methotrexate, trimethoprim), sulfasalazine, hydantoins. 

Drugs that may interact with sulfasalazine include digoxin, sulfonylureas, folic acid, cyclosporine, methotrexate, thiopurines, and warfarin. 

Sulfasalazine can inhibit the absorption of cardiac glycosides and folic acid. It may displace certain drugs, including warfarin, phenytoin, methotrexate, tolbutamide, chlorpropamide, and oral sulfonylureas, from their protein binding sites. Sulfasalazine can diminish the effectiveness of penicillins and estrogen-containing oral contraceptives. 

The disease modifying drugs (DMDs/ DMARDs) used are gold, d-penicillamine, hydroxychloroquine, sulfasalazine and immuno-suppressants like methotrexate, azathioprine, cyclosporin etc. 

When added to methotrexate background therapy, cyclosporine, chloroquine, hydroxychloroquine, leflunomide, infliximab, adalimumab, rituximab, and etanercept have all shown improved efficacy. In contrast, azathioprine, auranofin, or sulfasalazine plus methotrexate results in no additional therapeutic benefit. Other combinations have occasionally been used, including the combination of intramuscular gold with hydroxychloroquine. 

A 74-year-old woman with seronegative rheumatoid arthritis was given sulfasalazine followed by methotrexate, both of which were withdrawn because of adverse effects. She also took prednisone 10 mg/day. She developed acute abdominal pain and fever (38.7° C) with no chills. Her serum amylase was 269 IU/1, serum lipase... 

Penicillamine (Cuprimine), a derivative of penicillin, is officially classified as a chelating agent that is often used in the treatment of heavy metal intoxication (e.g., lead poisoning). In addition, this drug has been used in patients with severe rheumatoid arthritis, and seems to be as effective as other DMARDs such as methotrexate, sulfasalazine, and gold therapy.68 98 Penicillamine, however, tends to be substantially more toxic than other DMARDs, and is therefore used rarely in the treatment of specific patients with rheumatoid arthritis.68... 

Only trained medical personnel can prescribe DMARDs like aura-nofin, but there are others such as chloroquine, methotrexate, penicillamine, and sulfasalazine. Chloroquine was originally developed as an antimalarial drug but was found to have some anti-rheumatic activity. Methotrexate acts on the immune system and was particular favoured by doctors for the treatment of arthritis in the 1990s because it could be prescribed on a long-term basis. Penicillamine is effective but needs to be taken for many months before its benefits appear. Sulfasalazine was specifically developed as an anti-rheumatic drug and... 

Mercaptopurine Methotrexate Oral contraceptives p-Ami nosalicylate Phenobarbital Phenyloin Primidone Pyrimethamine Sulfasalazine Tetracycline Vinblastine... 

METHOTREXATE AMINOSALICYLATES-SULFASALAZINE t risk of hepatotoxicity with sulfasalazine Additive hepatotoxic effects. Sulfasalazine also competes with methotrexate for renal elimination Monitor closely for symptoms of liver failure. Check LFTs at the beginning of treatment then weekly until stable, and repeat if there is clinical suspicion of liver disease... 

Te use of NSAIDS and other anti-inflammatory therapies are similar to those used in other autoimmune arthritic disorders. Corticosteroid injections for severe pain and inflammation at specific joints are standard therapy. For severe forms of the disease immunomodulating anti-rheumatic drugs such as methotrexate and sulfasalazine are effective. As with other similar disorders, the biologic TNF a inhibitors are currently prescribed for severe Reiter s syndrome. 

Leflunomide has anti-inflammatory, immunosuppressive, and virustatic effects. Its efficacy has been demonstrated in patients with rheumatoid arthritis and psoriatic arthritis and other conditions in randomized, double-blind, placebo-controlled trials and other studies (8-32), and it was approved for treatment of adult rheumatoid arthritis in August 1998 (Table 1) (33). In three large phase III trials (US301, n = 482 MN301, n = 358 MN302, n = 999), leflunomide was as effective and well tolerated as methotrexate and sulfasalazine and superior to placebo (34). These data were confirmed by a meta-analysis (35,36). Leflunomide is therefore indicated for patients with rheumatoid arthritis who have failed first-line disease modifying anti-rheumatic drug therapy on the basis of efficacy, safety, and costs (36). It is effective as monotherapy and in combination with methotrexate or infliximab (6). 

Furst DE. The combination of methotrexate, sulfasalazine and hydroxychloroquine is highly effective in rheumatoid... 

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