Disease-Modifying Antirheumatic Drugs (DMARDs) are a class of medications used to treat autoimmune arthritis and related diseases. Their primary goal is to suppress abnormal immune activation, slow joint destruction and tissue damage, and delay disease progression. Unlike common analgesics or anti-inflammatory drugs, DMARDs require long-term, regular use to be effective, and are commonly used in the treatment of rheumatoid arthritis, Sjögren's syndrome, and juvenile arthritis.
These drugs modulate immune responses through various mechanisms, with some taking several weeks to months to show therapeutic effects. Physicians typically select between traditional synthetic DMARDs (csDMARDs) or biologic agents (bDMARDs) based on patient age, disease severity, and comorbidities to achieve optimal treatment outcomes.
Traditional DMARDs include methotrexate, leflunomide, and others, mainly by inhibiting cellular metabolism or DNA synthesis, thereby blocking immune cell activation. For example, methotrexate inhibits dihydrofolate reductase, reducing proliferation of T and B cells.
Biologic DMARDs target specific inflammatory cytokines such as tumor necrosis factor (TNF) or interleukins (IL). These monoclonal antibodies or receptor antagonists precisely neutralize pathogenic molecules; for instance, adalimumab binds to TNF-α, preventing its role in inducing arthritis. These two categories of drugs are often used in combination to enhance efficacy.
DMARDs are primarily used for autoimmune arthritis, including rheumatoid arthritis (RA), Sjögren's syndrome, and psoriatic arthritis. Initiating treatment early can effectively delay joint structural damage and prevent irreversible injury.
Additionally, DMARDs are suitable for juvenile idiopathic arthritis and joint symptoms of systemic lupus erythematosus. Some drugs, such as azathioprine, are also used for inflammatory bowel diseases, demonstrating their broad immunomodulatory functions.
Traditional DMARDs are often administered orally or via periodic injections, such as methotrexate at 2.5-25 mg weekly, with folic acid supplementation to reduce side effects. Biologics are usually given subcutaneously or intravenously, with dosages adjusted according to the specific drug, e.g., adalimumab 40 mg once weekly by subcutaneous injection.
Initial treatment requires regular monitoring of liver function, blood counts, and renal function, with dosage adjustments based on response. Biologics typically use fixed doses but are combined with baseline DMARDs to improve long-term outcomes.
DMARDs can repair some early joint damage and reduce long-term complications such as joint deformities. The high selectivity of biologics significantly decreases systemic immunosuppressive side effects.
Common side effects of traditional DMARDs include elevated liver enzymes, leukopenia, and gastrointestinal discomfort. Methotrexate may cause oral ulcers and should avoid alcohol intake. Biologics may increase infection risks, especially tuberculosis or severe viral infections.
Contraindications include severe liver or kidney dysfunction, active infections, and late pregnancy. Patients receiving biologics should undergo tuberculin testing beforehand to prevent reactivation of latent tuberculosis.
During treatment, blood counts, liver function, and antinuclear antibody levels should be monitored every 3-6 months. Pregnant women need to evaluate drug effects on the fetus; some medications should be discontinued before pregnancy.
Combining DMARDs with non-steroidal anti-inflammatory drugs (NSAIDs) may exacerbate gastrointestinal side effects. Combining with corticosteroids can enhance anti-inflammatory effects but increases the risk of excessive immunosuppression.
Using biologics with methotrexate can improve efficacy but requires monitoring for neutropenia. During biologic therapy, live vaccines are contraindicated, and patients should inform their healthcare providers of all medications and supplements they are taking.
Clinical studies show that early use of DMARDs can achieve remission in 70% of rheumatoid arthritis patients. Combination biologic therapy reduces joint destruction rates by 40-60%, with X-ray imaging showing significantly less bone erosion.
Long-term follow-up indicates that patients adhering to regular medication experience slower joint function decline, with improvements in quality of life indices (such as HAQ-DI) exceeding 30%. In refractory cases, 60% of patients regain responsiveness to treatment with biologics.
NSAIDs and corticosteroids can relieve pain and inflammation but do not prevent joint destruction. Traditional antirheumatic drugs (e.g., sulfasalazine) can be used as alternatives when DMARDs are contraindicated, although their efficacy is weaker.
Natural therapies such as fish oil or heat therapy are only supportive and cannot replace the disease-modifying effects of DMARDs. In certain cases (e.g., severe liver dysfunction), physicians may opt for selective COX-2 inhibitors, weighing cardiovascular risks.
Before initiating treatment, doctors usually arrange blood tests to assess liver and kidney function, blood cell counts, and infection markers (such as tuberculosis screening). Patients should inform their physicians of current medications, allergies, and family medical history. Additionally, vaccination against influenza or pneumonia may be recommended to reduce infection risks during therapy.
How should liver function abnormalities caused by DMARDs be monitored during use?Regular blood tests to monitor liver enzymes are necessary, typically every 3 to 6 months, depending on the specific medication. If elevated liver enzymes are detected, the physician may adjust the dose or switch drugs. Patients experiencing jaundice, severe fatigue, or dark urine should stop medication immediately and seek medical attention.
Can vaccines be administered or surgeries performed during DMARD therapy?Some DMARDs may suppress immunity; live vaccines (such as measles or varicella) should be administered before therapy or during treatment intervals. For surgeries, physicians may temporarily suspend medication to reduce bleeding or infection risks. Patients should communicate with their healthcare providers at least two weeks in advance of vaccination or surgery.
Should medication adjustments be made during pregnancy while on DMARDs?Certain DMARDs (e.g., methotrexate) may affect fetal development; women planning pregnancy or pregnant should discontinue these drugs. Safer alternatives like corticosteroids may be used. During pregnancy, strict contraception is required, and if pregnancy occurs, patients should inform their doctors immediately to avoid abrupt discontinuation that could worsen disease.
What if there is no improvement after 6 months of DMARD treatment?If no significant improvement occurs within 6 to 12 weeks, physicians will evaluate whether the dosage is sufficient or consider combining biologic agents. Response to therapy varies; different drug combinations may be attempted. Personalized adjustment plans are formulated based on disease activity indices, laboratory results, and patient symptoms, with regular follow-up visits.
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