Disease-modifying antirheumatic drug

Methotrexate

Hydroxychloroquine

Auranofin, a gold salt

Disease-modifying antirheumatic drugs (DMARDs) is a category of otherwise unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression. 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.

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), Sjogren's Syndrome, immune thrombocytopenic purpura (ITP), myasthenia gravis, sarcoidosis 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, a 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.

DMARDs have been classified as:

• synthetic (sDMARD)

* conventional synthetic and targeted synthetic DMARDs (csDMARDs and tsDMARDs, respectively)

* csDMARDs are the traditional drugs (such as methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, gold salts)

* tsDMARDs are drugs that were developed to target a particular molecular structure

• biological: original and biosimilar DMARDs (boDMARDs and bsDMARDs)

* bsDMARDs are those that have the same primary, secondary and tertiary structure as an original (boDMARD) and possess similar efficacy and safety as the original protein

Members

Drug	Mechanism
abatacept	T-cell costimulatory signal inhibitor
adalimumab	TNF inhibitor
azathioprine	Purine synthesis inhibitor
chloroquine and hydroxychloroquine (antimalarials)	Suppression of IL-1 & TNF-alpha, induce apoptosis of inflammatory cells and decrease chemotaxis
ciclosporin (Cyclosporin A)	calcineurin inhibitor
D-penicillamine	Reducing numbers of T-lymphocytes etc.
etanercept	decoy TNF receptor
golimumab	TNF inhibitor
gold salts (sodium aurothiomalate, auranofin)	unknown
infliximab	TNF inhibitor
leflunomide	Pyrimidine synthesis inhibitor
methotrexate (MTX)	Purine metabolism inhibitor
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.

Some of the drugs can be used in combination.

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.Furthermore, should DMARDs fail, tocilizumab can be used for tumor necrosis factor(TNF) inhibitor treatments in NICE guidance.

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.