What is DMARD (Disease-Modifying Antirheumatic Drug)?

What is a DMARD (Disease-Modifying Antirheumatic Drug)?

DMARDs are medications that modify the underlying disease process in inflammatory arthritis by slowing joint damage and preventing disability, rather than simply treating symptoms like pain relievers do. 1, 2

Classification of DMARDs

DMARDs are categorized into three main groups based on their molecular structure and mechanism 1:

Conventional Synthetic DMARDs (csDMARDs)

• Traditional small-molecule drugs including methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, and azathioprine 1, 2
• These work through various mechanisms including inhibition of purine synthesis, pyrimidine metabolism, and suppression of inflammatory cytokines 3
• Methotrexate is the anchor drug and first-line therapy for rheumatoid arthritis due to its established efficacy and safety profile 2, 4

Biological DMARDs (bDMARDs)

• Protein-based drugs that target specific components of the immune system 2
• Further subdivided into:
  • Biological originator DMARDs: TNF inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab), IL-6 receptor inhibitors (sarilumab, tocilizumab), costimulation inhibitors (abatacept), and anti-B cell agents (rituximab) 1, 2
  • Biosimilar DMARDs: Currently available for adalimumab, etanercept, infliximab, and rituximab 1
• These block inflammatory cytokines like TNF-α or target specific immune cells involved in the inflammatory cascade 2, 3

Targeted Synthetic DMARDs (tsDMARDs)

• Small molecule drugs specifically designed to target particular molecular structures 1, 5
• Include Janus kinase (JAK) inhibitors such as baricitinib, tofacitinib, and upadacitinib 1, 2
• Work intracellularly to block signaling pathways involved in inflammation 2

Primary Clinical Applications

DMARDs are the cornerstone of treatment for inflammatory arthritis conditions 2, 6:

• Rheumatoid arthritis - the primary indication, where early and continuous DMARD use slows joint damage and improves long-term outcomes 7, 6
• Psoriatic arthritis - reduces inflammation and prevents joint damage 2
• Ankylosing spondylitis - particularly bDMARDs for patients not responding to csDMARDs 2
• Juvenile idiopathic arthritis - DMARDs preferred over NSAID monotherapy 2, 3
• Other conditions including Crohn's disease and myasthenia gravis 3

Mechanism of Action

DMARDs work through diverse mechanisms to modify disease progression 2, 3:

• Inhibition of inflammatory cytokines (TNF-α, IL-1, IL-6) 3
• Induction of apoptosis of inflammatory cells 3
• Suppression of lymphocyte proliferation and immune cell function 8
• Intracellular pathway blockade (JAK inhibitors) 2
• Alteration of intracellular pH (antimalarials like hydroxychloroquine) 8

Key Treatment Principles

DMARDs should be started immediately after diagnosis to prevent irreversible joint damage and disability 2:

• Treatment follows a treat-to-target approach, adjusting therapy every 1-3 months until achieving remission or low disease activity 2, 4
• Methotrexate monotherapy (rapidly escalated to 20-25 mg weekly) is the initial strategy for most patients 2, 4
• Combination therapy with bDMARDs or tsDMARDs is added if inadequate response after 3 months in patients with moderate-to-high disease activity 2, 4
• Low-dose glucocorticoids (≤10 mg/day prednisone equivalent) serve as bridging therapy for less than 3 months while awaiting DMARD effect 2, 4

Important Safety Considerations

The major risk of bDMARDs and tsDMARDs relates to infections 1:

• Tuberculosis screening (TST or IGRA) required before initiating biologics or JAK inhibitors 4
• Hepatitis B and C screening mandatory before starting biologics 4
• Prophylactic antiviral therapy strongly recommended for hepatitis B core antibody positive patients initiating rituximab 2, 4
• TNF inhibitors contraindicated in heart failure (NYHA class III or IV) as they can worsen cardiac function 2, 4

Common Pitfalls to Avoid

• Failing to start DMARDs immediately after diagnosis leads to irreversible joint damage 2
• Inadequate methotrexate dosing - must rapidly escalate to 20-25 mg weekly for optimal effect 2
• Neglecting folic acid supplementation with methotrexate causes unnecessary side effects 2
• Insufficient disease activity monitoring - must assess every 1-3 months and adjust therapy accordingly 2, 4
• Prolonged glucocorticoid use beyond 3 months increases risk of cataracts, osteoporosis, and cardiovascular disease 4