Rheumatoid Arthritis treatment with DMARDs

Rheumatoid Arthritis treatment with Disease-modifying Anti-rheumatic Drugs is the standard of care worldwide. Previously, the management of patients with Rheumatoid arthritis centered around relieving pain and inflammation. However, this approach was not enough, as disease activity inside the joints would make a person crippled after a few years.

Read the latest ACR Rheumatoid Arthritis Treatment Guidelines

Currently available medicines to treat Rheumatoid Arthritis:

Medicines to treat Rheumatoid Arthritis include the following groups of medicines: rheumatoid arthritis treatment

  1. Analgesics and Non-steroidal Anti-inflammatory Drugs:

  2. Glucocorticoids:

  3. Conventional or Non-biological Disease-Modifying Anti-rheumatic Drugs:

  4. Biological Disease-Modifying Anti-rheumatic Drugs:

Rheumatoid Arthritis Treatment - A brief overview of the medications:

  • Analgesics and Non-steroidal Anti-inflammatory Drugs: 

    • These drugs are primarily used to treat pain, inflammation, and stiffness in patients with active arthritis.
    • NSAIDs are among the most commonly used drugs worldwide.
    • Common side effects of these drugs include heartburn, gastric ulcers, gastrointestinal bleeding, salt and fluid retention, heart, liver and kidney diseases.
    • These medicines are used in combination with conventional or biological DMARDs to rapidly relieve the pain and inflammation, however, they do not alter the disease activity.

  • Glucocorticoids:

    • Glucocorticoids have strong anti-inflammatory properties.
    • They may also exhibit mild disease-modifying properties in addition to relieving joint inflammation and pain.
    • They can be given as oral, Intramuscular, intravenous or administered directly into the joints.
    • Glucocorticoid use is limited by their long-term side effects like diabetes, hypertension, osteopenia (decreased mineralization of the bones), osteoporosis, increased susceptibility of infections, muscle weakness, hypogonadism, and heart diseases.

Conventional DMARDs:

  • Gold Salts and Penicillamine:

    • Gold Salts and penicillamine are rarely used nowadays because of the more potent and less toxic biological agents.

Gold salts require deep intramuscular injection and a test dose prior to regular administration.

Contraindications to Gold salts include pulmonary fibrosis, blood disorders, necrotizing enterocolitis, and Systemic lupus erythematosus.

Penicillamine is contraindicated in patients with systemic lupus erythematosus.

Furthermore, it may cause nephrotoxicity and should not be given simultaneously with gold salts.

  • Hydroxychloroquine:

    • Hydroxychloroquine may be advised to patients with a mild disease especially arthritis and in patients with cutaneous involvement.

  • Sulfasalazine:

    • This drug is used to treat rheumatoid arthritis and inflammatory bowel diseases.
    • It is relatively safe during pregnancy (pregnancy category B) and is, therefore, a preferred drug in young females who plan to conceive.
    • It should not be given to patients with allergy to sulfa drugs and should be used with caution in patients with liver diseases, cytopenias and with certain medicines (digoxin, warfarin and anti-diabetic medicines).

  • Methotrexate:

    • Methotrexate is an antifolate medicine used to treat a variety of conditions including autoimmune rheumatic diseases and cancers.
    • It is considered as the drug of choice for the treatment of Rheumatoid arthritis because of its safety and efficacy.
    • It is started at a low dose once weekly to a maximum dose of 25 mg per week.
    • It is contraindicated in pregnancy and severe liver diseases.
    • Side effects of methotrexate include cytopenias, hepato-toxicity, lung fibrosis, and gastrointestinal adverse effects.

  • Leflunomide:

    • Leflunomide is used to treat patients with rheumatoid arthritis as monotherapy or in combination with methotrexate.
    • It is usually given to patients who can not tolerate methotrexate and have contraindications to the biological DMARDs.
    • It is given as a loading dose (100 mg for three days) followed by a maintenance dose (20 mg/day).
    • It is contraindicated in pregnant patients and those with elevated liver enzymes (more than three times the upper limits of normal).
    • Other significant adverse effects include a rash, diarrhea, cytopenias, neuropathy, interstitial lung disease and infertility.

Biological DMARDs:

  • TNF Alpha inhibitors:

    • Currently, five drugs from this group have been recommended for the treatment of rheumatoid arthritis.
    • Studies have shown that these drugs have similar efficacy as methotrexate when used as monotherapy and are superior in combination with methotrexate to methotrexate/ TNF Alpha inhibitor monotherapy.

    • Etanercept:

      • Etanercept is licensed for the treatment of moderate to severely active Rheumatoid Arthritis as monotherapy or combination with methotrexate.
      • It is administered subcutaneously in a dose of 50 mg weekly or 25 mg twice weekly.
      • Compared to other DMARDs, it is relatively safe in pregnancy and classified as a pregnancy category B drug.
      • Important side effects of etanercept include reactivation of tuberculosis and hepatitis B infection, increased risks of serious infections that may require hospitalization, and certain hematological malignancies like lymphoma.
    • Infliximab:

      • Infliximab is used to treat moderately to severely active Rheumatoid Arthritis with Methotrexate.
      • It is given in the form of intravenous infusion in a dose of 3 mg/kg at 0, 2 weeks, and 6 weeks followed by 8 weeks thereafter.
      • It is also used to treat ankylosing spondylitis, inflammatory bowel disease, and psoriatic arthritis.
      • It is relatively safe during pregnancy (pregnancy category B).
      • Important side effects of infliximab include allergic reactions, reactivation of tuberculosis, and other serious infections, increased incidence of lymphoma and flare-up of demyelinating diseases like multiple sclerosis and optic neuritis.
    • Adalimumab:

      • Adalimumab is used to treat moderate to severely active arthritis as monotherapy or in combination with methotrexate.
      • It is given in a dose of 40 mg subcutaneously every other week with methotrexate or weekly in patients as a monotherapy.
      • It is relatively safe in pregnancy (category B). Important side effects include reactivation of infections (like tuberculosis and hepatitis B) and demyelinating diseases, increased incidence of hematological malignancies, hypersensitivity reactions, and hematological toxicity.
    • Golimumab:

      • This drug is used to treat active Rheumatoid arthritis as add-on therapy to methotrexate. It can not be combined with other biological DMARDs.
      • Golimumab is given subcutaneously (50 mg) every month.
      • There are no contraindications mentioned in the manufacturer's labeling.
      • However, like other biological DMARDs, the risk of serious infections and reactivation of tuberculosis, hepatitis B, and autoimmune disorders may rarely occur.
    • Certolizumab pegol: 

      • This drug is used to treat moderately to severely active Rheumatoid Arthritis and severe Crohn's colitis.
      • It is given as 400 mg initially, at two weeks and at 4 weeks.
      • The maintenance dose is 200 mg every other week or 400 mg monthly subcutaneously.
      • Adverse effects are similar to other biological DMARDs.

  • Interleukin 1 receptor antagonist (Anakinra):

    • This drug is used in moderately to severely active Rheumatoid arthritis who have failed one or more DMARDs.
    • It can be administered as monotherapy or in combination with other DMARDs other than TNF-receptor inhibitors.
    • It is given as a daily subcutaneous injection (100 mg).
    • Contraindications include allergy to anakinra or E.coli derived proteins.
    • It should be used with caution in patients with asthma and renal failure.
    • Like other DMARDs, it should be avoided in patients with infections as it may cause neutropenia.
    • Before starting the drug, the patients' immunization schedule should be up-to-date.

  • Interleukin 6 receptor antagonist (Tocilizumab):

    • Tocilizumab inhibits interleukin 6 receptors, minimizing the inflammatory process.
    • It is therefore used to treat moderately-to-severely active Rheumatoid Arthritis and systemic-onset Juvenile idiopathic arthritis.
    • It is given intravenously as 4 mg/kg every four weekly (maximum dose of 800 mg).
    • Adverse effects are similar to other DMARDs (reactivation of infections, Tuberculosis, hepatitis B, herpes zoster, and autoimmune diseases).
    • In addition, it should also be avoided in liver disease, patients with thrombocytopenia and neutropenia.
    • It should also be avoided in patients with suspected gastrointestinal perforation.
    • Furthermore, a lipid profile should also be monitored every 4 to 8 weeks.

  • T cell co-stimulator blocker (Abatacept):

    • Abatacept inhibits the activation of T-cells.
    • This drug is used to treat Rheumatoid arthritis and juvenile idiopathic arthritis.
    • It is given as an intravenous infusion of 500 to 1000 mg every month after the initial schedule.
    • It should be used with caution in patients with infections and COPD.

  • Anti CD-20 B cell depleting monoclonal antibody (Rituximab):

    • Rituximab is a monoclonal antibody that inhibits the CD-20 receptors on B cells.
    • It is used as an antineoplastic ( lymphoma and chronic lymphocytic leukemia), immunosuppressant and anti-rheumatic drug.
    • For the treatment of Rheumatoid arthritis, it is given as 1000 mg intravenous infusion on days 1 and 15 in combination with methotrexate.
    • Repeat doses may be given every 24 weeks.
    • Adverse effects include severe anaphylactic reactions, reactivation of infections including multifocal leukoencephalopathy.
    • It should also be used with caution in patients with cardiovascular diseases, respiratory diseases, and suspected bowel obstruction.

Read the latest ACR Rheumatoid Arthritis Treatment Guidelines


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