Antiarthritics


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.
Common antiarthritic drug classes include the following: disease-modifying antirheumatic drugs, biologic response modifiers, analgesics, non-steroidal anti-inflammatory drugs, and corticosteroids.

Types of arthritis

Osteoarthritis

is caused by the wear and tear damage to the joint's cartilage.
The compelling pharmacological recommendations for the treatment of OA are oral NSAIDs, topical NSAIDs, and intra-articular steroids. Other conditionally recommended therapies include acetaminophen, tramadol, duloxetine, chondroitin, and topical capsaicin.

Rheumatoid arthritis

is an inflammatory disease that's caused by an autoimmune condition. The condition occurs when bodily cells begin to attack and target their own healthy joint tissues resulting in redness, inflammation, and pain. Patients with RA may be given antiarthritics that are used to block inflammation and help prevent joint damage.
The typical first-line pharmacological recommendation for patients with symptomatic rheumatoid arthritis is DMARD monotherapy. In moderate or severe disease activity, it is recommended to combine conventional DMARDs, add a TNF-α inhibitors or a non-TNF biologic or tofacitinib.

Gout

is another common type of inflammatory arthritis that typically affects one joint at a time. Pharmacological treatment of gout typically relies on the management of flare-ups. Flare-ups are treated with the use of nonsteroidal anti-inflammatory drugs like ibuprofen, steroids, and/or the anti-inflammatory medication colchicine.

Juvenile rheumatoid arthritis

, the most common type of childhood arthritis, can cause permanent physical damage to joints. Pharmacological interventions include NSAIDs, intra-articular corticosteroid injections like triamcinolone hexacetonide, conventional DMARDs, and TNF inhibitors such as etanercept.

Medical use

Antiarthritic drugs are used to treat or prevent joint pain and joint diseases. These medications also provide symptomatic relief to common arthritic joint symptoms including swelling, tenderness, pain, stiffness, and decreased range of motion. These symptoms may persist or occur periodically and if symptoms are not managed, major complications may develop including permanent joint changes, chronic pain, and functional disabilities. Ultimately, antiarthritic treatments aim to achieve disease remission or low disease activity if remission cannot be achieved and thereby improving quality of life.
The pharmacological effects of antiarthritic medications are typically exerted through the reduction of inflammation, suppression of the immune system and/or aid in easing pain.

Disease-modifying antirheumatic drugs (DMARDs)

Disease-modifying antirheumatic drugs are often used to decrease inflammation at the site of injury for RA. DMARDs also act to relieve pain and decrease progression and worsening of RA. It mainly functions by slowing or stopping the immune system from attacking the joints.
Conventional DMARDs are known to be the first-line treatment for rheumatoid arthritis. Treatment can be a monotherapy or in combination with other anti-arthritic medications. Common DMARDs include oral methotrexate, leflunomide, or sulfasalazine.
Conventional DMARDs have a slow onset of action and can take 2–3 months to exhibit effect. Short-term bridging treatment with a corticosteroid is often considered when introducing a treatment with a new conventional DMARD. The use of short-term corticosteroids will help with a rapid symptomatic relief while waiting for the DMARD to exert effect.

Methotrexate

is considered to be the preferred conventional DMARD to treat RA. Route of administration includes oral tablets and liquids as well as intravenous and subcutaneous injections.

Mechanism of action

Methotrexate is a DMARD that acts as a competitive inhibitor on the enzyme dihydrofolate reductase and hinders the formation of tetrahydrofolate. Tetrahydrofolate is essential for the synthesis of purine and pyrimidine which consequently controls the formation of DNA and RNA that are responsible for the immune response and inflammation. By preventing the formation of tetrahydrofolate and the subsequent proteins, DMARDs suppress the immune response and reduce arthritis inflammation.

Side effects

Methotrexate is commonly associated with dose-related toxic effects involving the bone marrow and gastrointestinal tract. Folic acid may be given weekly to help diminish the frequency of side-effects. Methotrexate is also associated with acute and chronic liver damage.
Other adverse effects include:
Folic acid may be given by medical practitioners during the drug therapy using methotrexate. Folic acid acts to provide protection for the healthy cells in the human body. As such, it will help to reduce the side effects of methotrexate.

Contraindications

Contraindications of methotrexate include:
In addition, methotrexate is teratogenic and has been associated with fetal deaths. As a consequence, it is avoided during pregnancy.

Biologic response modifiers

are drugs classified as a special type of DMARDs. It is typically administered when conventional DMARDs do not work. It is genetically engineered to target various proteins that are involved in the immune response. The route of administration is available through intravenous or subcutaneous injection.
Biologic response modifiers are commonly used as a monotherapy or in combination with non-biologics, such as methotrexate. Combination of biologics is not advised due to limited additional benefit accompanied with a substantial increase in risks.
Biologic response modifiers can be divided into classes based on protein molecules that it inhibits such as tumor necrosis factor, interleukin-1, interleukin-6, and white blood cells like B cells or T cells.

Mechanism of action

Biologic response modifiers act by altering the immune response of the human body. The mechanism of action is either through interfering with the effect of cytokines, inhibiting the costimulation of T cell activation, or inhibiting B cells. Cytokines are proinflammatory and are responsible for regulating the human immune response.

TNF-α inhibitors

are the most commonly prescribed medication among biologic response modifiers used to treat arthritis. Patients with rheumatic conditions may have higher levels of TNF in the systemic circulation. As a result of increased levels of TNF, there would be more inflammation and persistent symptoms of arthritis. Certolizumab is the only TNF-α Inhibitor that can be administered during pregnancy.
Examples:
and IL-6 are particularly involved as proinflammatory cytokines contributing to arthritic symptoms. The inhibition of these cytokines is effective in reducing inflammation and consequently reducing the severity of arthritis.
Examples:
Selective costimulation modulator of T cells is a type of biologic that targets the inhibition of T cell activation as well as the selective blocking of the interaction between CD80 and CD86 receptors to CD28. To prevent CD28 interaction with the CD80/CD86 receptors, these drugs modulate by binding to these receptors on antigen presenting cells. As a result, this type of biologic inhibits T cell proliferation and B cell immunological response.
Abatacept is available as an antiarthritic medication for moderate to severe RA. This biologic can also be used to treat patients with juvenile rheumatoid arthritis.
Examples:
  • Abatacept

    B cells inhibitor

s, or B lymphocytes are a type of white blood cells that contribute to the pathogenesis of RA. B cells have a variety of functions including being an efficient APC, contribute to T cell activation, produce cytokines that promote the permeation of leukocytes into the joints and more. The therapeutic effect of B cells inhibitor is dependent on the disruption of these diverse functions.
Examples:
The adverse reactions of biologic response modifier therapies are associated with their mechanism of action that disrupts the immune homeostasis of the human body. These inhibitory biologics cause suppression of the immune response resulting in an increase in risk and susceptibility to infection.
Common infections include:
It may also cause mild side effects such as headache and nausea.

Janus kinase inhibitors

are used to treat RA. Similar to biologic response modifiers, these drugs act to reduce immune response. However, these medications are available in tablet formulations, unlike biologics.
Examples:
JAK inhibitors act by inhibiting Janus kinases which consequently affect a cascade of enzymes responsible for signaling a variety of cytokine and haematopoietic growth factor receptors. As a consequence, inhibiting these enzymes leads to the control and suppression of immune pathways.