Disease-modifying antirheumatic drug

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Methotrexate Methotrexate skeletal.svg
Methotrexate
Hydroxychloroquine Hydroxychloroquine.svg
Hydroxychloroquine
Auranofin, a gold salt Auranofin-2D-skeletal.png
Auranofin, a gold salt

Disease-modifying antirheumatic drugs (DMARDs) comprise a category of otherwise unrelated disease-modifying drugs defined by their use in rheumatoid arthritis to slow down disease progression. [1] [2] The term is often used in contrast to nonsteroidal anti-inflammatory drugs (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).

Contents

The term "antirheumatic" can be used in similar contexts, but without making a claim about an effect on the disease course. [3] 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). [4]

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, lupus erythematosus, Sjögren syndrome, immune thrombocytopenic purpura, myasthenia gravis, sarcoidosis, and various others. [ citation needed ]

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, reduced haemoglobin level, raised rheumatoid factor level, and more recently, a raised C-reactive protein level.[ citation needed ] More recently, the term has been used to indicate a drug that reduces the rate of damage to bone and cartilage.[ citation needed ] 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 their main therapeutical benefit.[ citation needed ]

Subdivision

DMARDs have been classified as: [5]

Members

DrugMechanismType
abatacept T-cell costimulatory signal inhibitorbDMARD
adalimumab TNF inhibitor bDMARD
anakinra IL-1 receptor antagonistbDMARD
apremilast phosphodiesterase 4 (PDE4) inhibitortsDMARD
azathioprine Purine synthesis inhibitor unknown
baricitinib JAK1 and JAK2 inhibitortsDMARD
certolizumab pegol TNF inhibitor bDMARD
chloroquine (anti-malarial)Suppression of IL-1, induce apoptosis of inflammatory cells and decrease chemotaxis unknown
ciclosporin (Cyclosporin A) calcineurin inhibitor unknown
D-penicillamine (seldom used today)Reducing numbers of T-lymphocytes etc.unknown
etanercept decoy TNF receptor bDMARD
filgotinib Janus kinase (JAK) inhibitortsDMARD
golimumab TNF inhibitor bDMARD
gold salts (sodium aurothiomalate, auranofin) (seldom used today)unknowncsDMARD
hydroxychloroquine (anti-malarial)TNF-alpha, induce apoptosis of inflammatory cells and decrease chemotaxis csDMARD
infliximab TNF inhibitor bDMARD
leflunomide Pyrimidine synthesis inhibitor csDMARD
methotrexate (MTX) Purine metabolism inhibitorcsDMARD
minocycline 5-LO inhibitor unknown
rituximab chimeric monoclonal antibody against CD20 on B-cell surfacebDMARD
sarilumab IL-6 receptor antagonistbDMARD
secukinumab IL-17 inhibitorbDMARD
sulfasalazine (SSZ)Suppression of IL-1 & TNF-alpha, induce apoptosis of inflammatory cells and increase chemotactic factors csDMARD
tocilizumab IL-6 receptor antagonistbDMARD
tofacitinib Janus kinase (JAK) inhibitortsDMARD
ustekinumab IL-12 and IL-23 inhibitorbDMARD

Although these agents operate by different mechanisms, many of them can have similar impacts upon the course of a condition. [6] Some of the drugs can be used in combination. [7] A common triple therapy for rheumatoid arthritis is methotrexate, sulfasalazine, and hydroxychloroquine.[ citation needed ]

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. [8]

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 effects.[ citation needed ]

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 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.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Arthritis</span> Type of joint disorder

Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some types of arthritis, other organs are also affected. Onset can be gradual or sudden.

<span class="mw-page-title-main">Rheumatoid arthritis</span> Type of autoimmune 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 involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body, including skin, eyes, lungs, heart, nerves, and blood. This may result in a low red blood cell count, inflammation around the lungs, and inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months.

Rheumatology is a branch of medicine devoted to the diagnosis and management of disorders whose common feature is inflammation in the bones, muscles, joints, and internal organs. Rheumatology covers more than 100 different complex diseases, collectively known as rheumatic diseases, which includes many forms of arthritis as well as lupus and Sjögren's syndrome. Doctors who have undergone formal training in rheumatology are called rheumatologists.

<span class="mw-page-title-main">Immunosuppressive drug</span> Drug that inhibits activity of immune system

Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system.

<span class="mw-page-title-main">Methotrexate</span> Chemotherapy and immunosuppressant medication

Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma. Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease. It can be given by mouth or by injection.

<span class="mw-page-title-main">Ankylosing spondylitis</span> Type of arthritis of the spine

Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine, typically where the spine joins the pelvis. With AS, eye, bowel problems and back pain may occur. Joint mobility in the affected areas sometimes worsens over time. Ankylosing spondylitis is believed to involve a combination of genetic and environmental factors. More than 85% of people affected in the UK have a specific human leukocyte antigen known as the HLA-B27 antigen. The underlying mechanism is believed to be autoimmune or autoinflammatory. Diagnosis is based on symptoms with support from medical imaging and blood tests. AS is a type of seronegative spondyloarthropathy, meaning that tests show no presence of rheumatoid factor (RF) antibodies.

<span class="mw-page-title-main">Psoriatic arthritis</span> Long-term inflammatory arthritis

Psoriatic arthritis (PsA) is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. This often happens in association with changes to the nails such as small depressions in the nail (pitting), thickening of the nails, and detachment of the nail from the nailbed. Skin changes consistent with psoriasis frequently occur before the onset of psoriatic arthritis but psoriatic arthritis can precede the rash in 15% of affected individuals. It is classified as a type of seronegative spondyloarthropathy.

<span class="mw-page-title-main">Sulfasalazine</span> Chemical compound

Sulfasalazine, sold under the brand name Azulfidine among others, is a medication used to treat rheumatoid arthritis, ulcerative colitis, and Crohn's disease. It is considered by some to be a first-line treatment in rheumatoid arthritis. It is taken by mouth or can be administered rectally.

<span class="mw-page-title-main">Cyclophosphamide</span> Medication used as chemotherapy and to suppress the immune system

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, small cell lung cancer, neuroblastoma, and sarcoma. As an immune suppressor it is used in nephrotic syndrome, granulomatosis with polyangiitis, and following organ transplant, among other conditions. It is taken by mouth or injection into a vein.

<span class="mw-page-title-main">Anakinra</span> Pharmaceutical drug

Anakinra, sold under the brand name Kineret, is a biopharmaceutical medication used to treat rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease. It is a slightly modified recombinant version of the human interleukin 1 receptor antagonist protein. It is marketed by Swedish Orphan Biovitrum. Anakinra is administered by subcutaneous injection.

<span class="mw-page-title-main">Leflunomide</span> Chemical compound

Leflunomide, sold under the brand name Arava among others, is an immunosuppressive disease-modifying antirheumatic drug (DMARD), used in active moderate-to-severe rheumatoid arthritis and psoriatic arthritis. It is a pyrimidine synthesis inhibitor that works by inhibiting dihydroorotate dehydrogenase.

Biological response modifiers (BRMs) are substances that modify immune responses. They can be endogenous or exogenous, and they can either enhance an immune response or suppress it. Some of these substances arouse the body's response to an infection, and others can keep the response from becoming excessive. Thus they serve as immunomodulators in immunotherapy, which can be helpful in treating cancer and in treating autoimmune diseases, such as some kinds of arthritis and dermatitis. Most BRMs are biopharmaceuticals (biologics), including monoclonal antibodies, interleukin 2, interferons, and various types of colony-stimulating factors. "Immunotherapy makes use of BRMs to enhance the activity of the immune system to increase the body's natural defense mechanisms against cancer", whereas BRMs for rheumatoid arthritis aim to reduce inflammation.

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 COVID‑19. It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was jointly developed by Osaka University and Chugai, and was licensed in 2003 by Hoffmann-La Roche.

Rheumatoid lung disease is a disease of the lung associated with RA, rheumatoid arthritis. Rheumatoid lung disease is characterized by pleural effusion, pulmonary fibrosis, lung nodules and pulmonary hypertension. Common symptoms associated with the disease include shortness of breath, cough, chest pain and fever. It is estimated that about one quarter of people with rheumatoid arthritis develop this disease, which are more likely to develop among elderly men with a history of smoking.

Sarilumab, sold under the brand name Kevzara, is a human monoclonal antibody medication against the interleukin-6 receptor. Regeneron Pharmaceuticals and Sanofi developed the drug for the treatment of rheumatoid arthritis (RA), for which it received US FDA approval on 22 May 2017 and European Medicines Agency approval on 23 June 2017.

<span class="mw-page-title-main">Filgotinib</span> Chemical compound

Filgotinib, sold under the brand name Jyseleca, is a medication used for the treatment of rheumatoid arthritis (RA). It was developed by the Belgian-Dutch biotech company Galapagos NV.

<span class="mw-page-title-main">ERA-63</span> Chemical compound

ERA-63, also known as ORG-37663, as well as 3-methylene-7α-methyl-17α-ethynylestra-5(10)-en-17β-ol, is a synthetic, steroidal estrogen and a selective agonist of the ERα that was under development for the treatment of rheumatoid arthritis but was never marketed. The drug produced estrogenic effects but failed to show effectiveness for rheumatoid arthritis in a phase IIa clinical study. A large clinical trial also found that prinaberel (ERB-041), a selective ERβ agonist, was ineffective in the treatment of rheumatoid arthritis in spite of activity in preclinical models.

<span class="mw-page-title-main">Peficitinib</span> Chemical compound

Peficitinib is a pharmaceutical drug used for the treatment of rheumatoid arthritis. It belongs to the class of drugs known as Janus kinase inhibitors.

<span class="mw-page-title-main">Upadacitinib</span> Chemical compound (medication)

Upadacitinib, sold under the brand name Rinvoq, is a medication used for the treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and axial spondyloarthritis. Upadacitinib is a Janus kinase (JAK) inhibitor that works by blocking the action of enzymes called Janus kinases. These enzymes are involved in setting up processes that lead to inflammation, and blocking their effect brings inflammation in the joints under control.

<span class="mw-page-title-main">Antiarthritics</span> Drug class

An antiarthritic is any drug used to relieve or prevent arthritic symptoms, such as joint pain or joint stiffness. Depending on the antiarthritic drug class, it is used for managing pain, reducing inflammation or acting as an immunosuppressant. These drugs are typically given orally, topically or through administration by injection. The choice of antiarthritic medication is often determined by the nature of arthritis, the severity of symptoms as well as other factors, such as the tolerability of side effects.

References

  1. "disease-modifying antirheumatic drug" "at Dorland's Medical Dictionary
  2. "Disease modifying antirheumatic drugs (DMARDs)". Archived from the original on 2009-04-26. Retrieved 2008-10-22.
  3. "antirheumatic" "at Dorland's Medical Dictionary
  4. Buer, Jonas Kure (2015). "A history of the term "DMARD"". Inflammopharmacology. 23 (4): 163–71. doi:10.1007/s10787-015-0232-5. PMC   4508364 . PMID   26002695.
  5. Smolen JS, van der Heijde D, Machold KP, Aletaha D, Landewé R. Proposal for a new nomenclature of disease-modifying antirheumatic drugs. Ann Rheum Dis. 2014 Jan;73(1):3–5. doi : 10.1136/annrheumdis-2013-204317.
  6. 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): 251–56. doi:10.1097/BOR.0b013e3282fb7caa. PMID   18388514. S2CID   7278909.
  7. 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.
  8. "Tocilizumab for the Treatment of Rheumatoid Arthritis (TA247)". mims.co.uk. Retrieved 11 April 2018.