DMARD drugs

Disease-modifying Anti-rheumatic Drugs (DMARDs)... 

The treatment approach to RA has undergone a major evolutionary change in recent years with a move away from predominantly symptomatic treatment approaches towards much earlier intervention with diseasemodifying anti-rheumatic drug (DMARD) therapy and... 

DL-CFU Dendritic cell/Langerhans cell colony forming DLE Discoid lupus erythematosus DMARD Disease-modifying antirheumatic drug... 

FIGURE 54-2. Outl ine of the management of rheumatoid arthritis. (From Guidelines for the management of rheumatoid arthritis 2002 update. Arthritis Rheum 2002 46(2) 328-346, with permission.) DMARD, disease-modifying antirheumatic drug NSAID, nonsteroidal antiinflammatory drug ... 

DMARD disease-modifying antirheumatic drug ESR erythrocyte sedimentation rate... 

A disease-modifying antirheumatic drug (DMARD) should be started within the first 3 months of symptom onset (Fig. 4-1). DMARDs should be used in all patients except those with limited disease. Early use of DMARDs results in a more favorable outcome and can reduce mortality. 

Nonsteroidal antiinflammatory drugs (NSAIDs) and/or corticosteroids may be used for symptomatic relief if needed. They provide relatively rapid improvement compared with DMARDs, which may take weeks to months before benefit is seen. However, NSAIDs have no impact on disease progression, and corticosteroids have the potential for long-term complications. 

Hydroxychloroquine lacks the myelosuppressive, hepatic, and renal tox-icities seen with some other DMARDs, which simplifies monitoring. Its onset may be delayed for up to 6 weeks, but the drug should not be considered a therapeutic failure until after 6 months of therapy with no... 

For over the past two decades, MTX has been the fnst-hne DMARD in RA because of its well-established efficacy and safety (2-4). However, the response among patients to MTX can be quite variable, ranging from 46% to 65% (5,6). The exact mechanism of action of the drug in RA remains unclear however, it is beheved that MTX s effects in RA occur because of its effects on the intracellular folate and adenosine pathways. 

Sulfasalazine is another DMARD often used in the treatment of RA. It is estimated that 20-30% of RA patients on SSZ report adverse drug reactions. Adverse drug events of SSZ are G1 and hematologic. 

Polyarticular-course juvenile rheumatoid arthritis (JRA) For reducing signs and symptoms of moderately to severely active polyarticular-course JRA in patients who have had an inadequate response to at least 1 disease-modifying antirheumatic drug (DMARD). 

Unfortunately, a substantial proportion of patients with autoimmune inflammatory diseases have become refractory to NSAIDs, and/or oral or intravenous Disease Modifying Anti Rheumatic Drugs (DMARDs). However, oral combinations of DMARDs generate better outcomes compared to single drug therapy in autoimmune disease. Even autoimmune diseases can become refractory to oral DMARD combinations. 

Outcome measurements used in the evaluation of the outcome of treatment of RA with sulfasalazine, parenteral gold salts, D-penicillamine, hydroxychloroquine, prednisolone, MTX, cyclophosphamide (CyC), and azathioprine in single drug therapy cannot be compared with endpoints used in SBC-5-lMNs and biological-DMARDs combined with MTX. 

DMARD Refractory Lupus Nephritis is considered to be in remission when the SLAM-R Score is suppressed to zero, ESR is suppressed to 10 mm (male 5 mm) and 24 hours Micro-albuminuria is suppressed to <30 mg (normal <30 mg). Remission with oral drugs (RworalDs) is defined when Remission is maintained with MME and/or CyS for at least 2 years and remission without drug (RwD) when after 2 years therapy, oral drugs are tapered off with a sustained remission for at least 2 years. 

Sulfasalazine is contraindicated in individuals with hypersensitivity to salicylates, sulfonamides, sulfonylureas, and certain diuretics (furosemide, thiazides, and carbonic anhydrase inhibitors). Because it can cause kernicterus, sulfasalazine is contraindicated in infants and children under 2 years of age. Sulfasalazine passes into breast milk and is therefore contraindicated for nursing mothers. Similarly, pregnant women near term should not use this drug, although it appears to be the safest of the DMARDs during early pregnancy. 

Hydroxychloroquine Plaquenil) and chloroquine Ara-len) are 4-aminoquinoline antimalarial drugs that possess modest DMARD activity. They are indicated for the treatment of rheumatoid arthritis and systemic lupus erythematosus their use as antimalarials is detailed in Chapter 53. The onset of action of these drugs is longer than that of other DMARDs, and their side effects are relatively mild. Because of this, these agents show promise as ingredients of combination therapies for rheumatoid arthritis. 

Two recently introduced biological therapies were designed to interfere with the inflammatory cascade initiate by TNF-a. Etanercept (Enbrel) is indicated for the treatment of moderate to severe rheumatoid arthritis in individuals over age 4. Infliximab in conjunction with methotrexate (Remicade) is approved for use by adults in the treatment of rheumatoid arthritis. It is also indicated for therapy of Crohn s disease. Over the short term, the efficacy of these drugs in the treatment of rheumatoid arthritis appears to be superior to that of methotrexate alone however, their ability to prevent bone erosion for longer than 24 months must be further studied. The cost of both drugs is significantly higher than that of the other DMARDs. 

Anakinra (Kineret) is the first antirheumatic agent that acts by blocking the action of IL-1. This drug was recently approved for the treatment of moderately to severely active rheumatoid arthritis in adults who have not responded to therapy with one or more DMARDs. Anakinra may be used alone or in combination with DMARDs other than the TNF antagonists. Clinical trials have shown anakinra to be more effective than placebo, either alone or in conjunction with methotrexate. 

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

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