Disease-modifying antirheumatic drugs (DMARDs) is a category of otherwise unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression.[1][2] The term is often used in contrast to non-steroidal anti-inflammatory drug (which refers to agents that treat the inflammation but not the underlying cause) and steroids (which blunt the immune response but are insufficient to slow down the progression of the disease).
The term "antirheumatic" can be used in similar contexts, but without making a claim about an effect on the course.[3]
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Terminology
Although their use was first propagated in rheumatoid arthritis (hence their name) the term has come to pertain to many other diseases, such as Crohn's disease, lupus erythematosus (SLE), immune thrombocytopenic purpura (ITP), myasthenia gravis and various others. Many of these are autoimmune disorders, but others, such as ulcerative colitis, are probably not (there is no consensus on this).
The term was originally introduced to indicate a drug that reduced evidence of processes thought to underlie the disease, such as a raised erythrocyte sedimentation rate, reduced haemoglobin level, raised rheumatoid factor level and more recently, raised C-reactive protein level. More recently, the term has been used to indicate a drug that reduces the rate of damage to bone and cartilage. DMARDs can be further subdivided into traditional small molecular mass drugs synthesised chemically and newer 'biological' agents produced through genetic engineering.
Some DMARDs (e.g. the Purine synthesis inhibitors) are mild chemotherapeutics but use a side-effect of chemotherapy - immunosuppression - as its main therapeutical benefit.
Members
Drug | Mechanism |
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adalimumab | TNF inhibitor |
azathioprine | Purine synthesis inhibitor |
chloroquine and hydroxychloroquine (antimalarials) | Suppression of IL-1 & TNF-alpha, induce apoptosis of inflammatory cells and increase chemotactic factors |
ciclosporin (Cyclosporin A) | calcineurin inhibitor |
D-penicillamine | Reducing numbers of T-lymphocytes etc. |
etanercept | TNF inhibitor |
golimumab | TNF inhibitor |
gold salts (sodium aurothiomalate, auranofin) | unknown - proposed mechanism: inhibits macrophage activation |
infliximab | TNF inhibitor |
leflunomide | Pyrimidine synthesis inhibitor |
methotrexate (MTX) | Antifolate |
minocycline | 5-LO inhibitor |
rituximab | chimeric monoclonal antibody against CD20 on B-cell surface |
sulfasalazine (SSZ) | Suppression of IL-1 & TNF-alpha, induce apoptosis of inflammatory cells and increase chemotactic factors |
Although these agents operate by different mechanisms, many of them can have similar impact upon the course of a condition.[4]
Some of the drugs can be used in combination.[5]
Alternatives
When treatment with DMARDs fails, cyclophosphamide or steroid pulse therapy is often used to stabilise uncontrolled autoimmune disease. Some severe autoimmune diseases are being treated with bone marrow transplants in clinical trials, usually after cyclophosphamide therapy has failed.
Combinations of DMARDs are often used together, because each drug in the combination can be used in smaller dosages than if it were given alone, thus reducing the risk of side effects.
Many patients receive an NSAID and at least one DMARD, sometimes with low-dose oral glucocorticoids. If disease remission is observed, regular NSAIDs or glucocorticoid treatment may no longer be needed. DMARDs help control arthritis but do not cure the disease. For that reason, if remission or optimal control is achieved with a DMARD, it is often continued at a maintenance dosage. Discontinuing a DMARD may reactivate disease or cause a “rebound flare”, with no assurance that disease control will be reestablished upon resumption of the medication, according to Arthritis & Rheumatism.[6]
References
- ^ "disease-modifying antirheumatic drug" at Dorland's Medical Dictionary
- ^ "Disease modifying antirheumatic drugs (DMARDs)". http://www.uptodate.com/patients/content/topic.do?topicKey=arth_rhe/5016.
- ^ "antirheumatic" at Dorland's Medical Dictionary
- ^ Nandi P, Kingsley GH, Scott DL (May 2008). "Disease-modifying antirheumatic drugs other than methotrexate in rheumatoid arthritis and seronegative arthritis". Current opinion in rheumatology 20 (3): 251–6. doi:10.1097/BOR.0b013e3282fb7caa. PMID 18388514. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00002281-200805000-00005.
- ^ Capell HA, Madhok R, Porter DR, et al. (February 2007). "Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double‐blind placebo‐controlled MASCOT study". Annals of the rheumatic diseases 66 (2): 235–41. doi:10.1136/ard.2006.057133. PMC 1798490. PMID 16926184. http://ard.bmj.com/cgi/pmidlookup?view=long&pmid=16926184.
- ^ Blog Article on DMARDS DMARDs: Prescription Rheumatoid Arthritis Medications
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