Disease-modifying antirheumatic drugs (DMARDs) comprise a category of otherwise unrelated
disease-modifying drugs A disease-modifying treatment, disease-modifying drug, or disease-modifying therapy is a treatment that delays or slows the progression of a disease by targeting its underlying cause. They are distinguished from symptomatic treatments that treat th ...
defined by their use in
rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
to slow down disease progression.
The term is often used in contrast to
nonsteroidal anti-inflammatory drug
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
s (which refers to agents that treat the
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
, but not the underlying cause) and
steroids
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
(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 disease course. Other terms that have historically been used to refer to the same group of drugs are "remission-inducing drugs" (RIDs) and "slow-acting antirheumatic drugs" (SAARDs).
Terminology
Although the use of the term DMARDs was first propagated in rheumatoid arthritis (hence their name), the term has come to pertain to many other diseases, such as
Crohn's disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...
,
lupus erythematosus
Lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blo ...
,
Sjögren syndrome
Sjögren syndrome or Sjögren's syndrome (SjS, SS) is a Chronic disease, long-term autoimmune disease that affects the body's moisture-producing (lacrimal and salivary) glands, and often seriously affects other organ systems, such as the lungs, k ...
,
immune thrombocytopenic purpura
Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is a type of thrombocytopenic purpura defined as an isolated low platelet count with a normal bone marrow in the absence of othe ...
,
myasthenia gravis
Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, dro ...
,
sarcoidosis
Sarcoidosis (also known as ''Besnier-Boeck-Schaumann disease'') is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly af ...
, and various others.
The term was originally introduced to indicate a drug that reduces evidence of processes thought to underlie the disease, such as a raised
erythrocyte sedimentation rate
The erythrocyte sedimentation rate (ESR or sed rate) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of ...
, reduced
haemoglobin
Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...
level, raised
rheumatoid factor level, and more recently, a raised
C-reactive protein
C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin-6 ...
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 inhibitor
Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.
Biosynthesis
Purines are biologically synthesized as nucleotides and in particular as ribotides, i.e. bases attached to r ...
s) are mild
chemotherapeutics
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
, but use a side effect of chemotherapy—''
immunosuppression
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...
''—as their main therapeutical benefit.
Subdivision
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 (bDMARD) can be further separated into original and
biosimilar
A biosimilar (also known as follow-on biologic or subsequent entry biologic) is a biologic medical product that is almost an identical copy of an original product that is manufactured by a different company. Biosimilars are officially approved ...
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
Although these agents operate by different mechanisms, many of them can have similar impacts upon the course of a condition.
Some of the drugs can be used in combination.
A common triple therapy for rheumatoid arthritis is methotrexate, sulfasalazine, and hydroxychloroquine.
Alternatives
When treatment with DMARDs fails,
cyclophosphamide
Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
or
steroid
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
pulse therapy is often used to stabilise uncontrolled autoimmune disease. Some severe autoimmune diseases are being treated with
bone marrow transplant
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...
s in
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
s, usually after cyclophosphamide therapy has failed. Furthermore, should DMARDs fail,
tocilizumab
Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, a severe form of arthritis in children, and COVID19. It is a hu ...
can be used for
tumor necrosis factor (TNF) inhibitor treatments in
NICE
Nice ( , ; Niçard: , classical norm, or , nonstandard, ; it, Nizza ; lij, Nissa; grc, Νίκαια; la, Nicaea) is the prefecture of the Alpes-Maritimes department in France. The Nice agglomeration extends far beyond the administrative c ...
guidance.
Combinations of DMARDs are often used, because each drug in the combination can be used in a smaller dose than if it were given alone, thus reducing the risk of
side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
s.
Many patients receive an NSAID and at least one DMARD, sometimes with low-dose oral
glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
s. 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 as a maintenance dosage. Discontinuing a DMARD may reactivate disease or cause a "rebound flare", with no assurance that disease control will be re-established upon resumption of the medication.
References
{{Antirheumatic products