What are the classifications and examples of anti-rheumatoid drugs, including Disease-Modifying Antirheumatic Drugs (DMARDs), biologic response modifiers (biologics), Janus Kinase (JAK) inhibitors, and glucocorticoids?

Anti-Rheumatoid Drug Classification

Anti-rheumatoid drugs are systematically classified into four main categories: conventional synthetic DMARDs (csDMARDs), biological DMARDs (bDMARDs), targeted synthetic DMARDs (tsDMARDs), and glucocorticoids, with additional immunosuppressants used in specific clinical scenarios. 1

1. Conventional Synthetic DMARDs (csDMARDs)

Core agents:

• Methotrexate - the anchor drug and first-line therapy 1, 2
• Leflunomide - alternative first-line option 1
• Sulfasalazine - alternative first-line option 1

Agents with mild immunomodulatory effects (often listed separately):

• Hydroxychloroquine - exempted from standard csDMARD category due to minimal immunosuppressive effect 1
• Sulfasalazine - sometimes specifically named due to milder effects 1

Traditional agents (less commonly used):

• Gold salts 3
• Azathioprine 4

2. Biological DMARDs (bDMARDs)

TNF Inhibitors (TNFi)

Five approved agents:

• Adalimumab (subcutaneous) 1
• Certolizumab pegol (subcutaneous) 1
• Etanercept (subcutaneous) 1
• Golimumab (subcutaneous) 1
• Infliximab (intravenous) 1, 5

Non-TNF Biologics

T-cell costimulation blocker:

• Abatacept 1

B-cell depleting agent:

• Rituximab 1

IL-6 pathway inhibitors:

• Tocilizumab 1
• Sarilumab 1

IL-1 inhibitor:

• Anakinra 3, 6

Biosimilar DMARDs (bsDMARDs)

• EMA-approved and FDA-approved biosimilars of the above biological originators 1

3. Targeted Synthetic DMARDs (tsDMARDs)

Janus Kinase (JAK) Inhibitors:

• Tofacitinib 1
• Baricitinib 1
• Filgotinib 1
• Upadacitinib 1, 7

Other targeted agents:

• Fostamatinib 3
• Apremilast (PDE4 inhibitor, exempted from standard tsDMARD infection risk category) 1

4. Glucocorticoids

Used as bridging therapy:

• Low-dose glucocorticoids (≤10 mg/day prednisone equivalent) 1
• Various dose regimens and routes of administration (oral, intramuscular, intra-articular) 1
• Should be tapered as rapidly as clinically feasible 1

5. Other Immunosuppressants

Used in specific clinical scenarios:

• Cyclophosphamide 1
• Mycophenolate mofetil 1
• Azathioprine 1
• Ciclosporin 1
• Tacrolimus 1

Key Clinical Considerations

Treatment hierarchy: Methotrexate remains the anchor drug, with escalation to bDMARDs or tsDMARDs when csDMARDs fail in patients with poor prognostic factors (autoantibodies, high disease activity, early erosions) 1, 2.

Combination therapy: bDMARDs and tsDMARDs should be combined with a csDMARD for optimal efficacy, though IL-6 pathway inhibitors and tsDMARDs may have advantages as monotherapy when csDMARDs cannot be used 1, 7.

Nomenclature consensus: The four-category system (csDMARDs, bDMARDs, tsDMARDs, glucocorticoids) represents current EULAR consensus, though the rheumatology community continues to refine terminology 1, 3.