Classification of Drugs for Rheumatoid Arthritis
Drugs for rheumatoid arthritis are classified into four main categories: conventional synthetic DMARDs (csDMARDs), biological DMARDs (bDMARDs), targeted synthetic DMARDs (tsDMARDs), and symptomatic agents including glucocorticoids and NSAIDs. 1
Primary Drug Classifications
1. Conventional Synthetic DMARDs (csDMARDs)
These are the foundational medications for RA treatment:
- Methotrexate (first-line agent) 1
- Leflunomide
- Sulfasalazine
- Hydroxychloroquine
Methotrexate should be part of the first treatment strategy and serves as the anchor drug for RA management 1. When methotrexate is contraindicated or not tolerated, leflunomide or sulfasalazine should be considered 1.
2. Biological DMARDs (bDMARDs)
These are subdivided by their mechanism of action:
TNF Inhibitors:
- Adalimumab
- Certolizumab pegol
- Etanercept
- Golimumab
- Infliximab (including biosimilars) 1
Non-TNF Biologics:
- IL-6 pathway inhibitors: Tocilizumab, Sarilumab
- T-cell costimulation blocker: Abatacept
- Anti-B cell (CD20): Rituximab 1
3. Targeted Synthetic DMARDs (tsDMARDs)
Currently consists of Janus kinase (JAK) inhibitors:
- Tofacitinib
- Baricitinib
- Filgotinib
- Upadacitinib 1
These oral agents have comparable efficacy to bDMARDs and may have advantages when used as monotherapy, particularly IL-6 inhibitors and JAK inhibitors 1.
4. Symptomatic/Adjunctive Agents
Glucocorticoids:
- Should be used short-term when initiating or changing csDMARDs
- Must be tapered as rapidly as clinically feasible
- Low-dose defined as <7.5 mg/day prednisone equivalent 1
NSAIDs:
Hierarchical Treatment Algorithm
The classification system directly informs treatment sequencing 1:
First-line: csDMARD (methotrexate) + short-term glucocorticoids
Second-line (if target not met within 3-6 months):
- Without poor prognostic factors: Try another csDMARD 1
- With poor prognostic factors: Add bDMARD or tsDMARD to csDMARD 1
Third-line (if bDMARD/tsDMARD fails):
- Switch to another bDMARD or tsDMARD
- Can switch within same class (e.g., TNF to TNF) or to different mechanism 1
Important Clinical Distinctions
Poor prognostic factors that trigger escalation to biologics/targeted synthetics include 1:
- Persistently moderate/high disease activity despite csDMARD therapy
- High acute phase reactants
- High swollen joint count
- Presence of RF and/or ACPA (especially high levels)
- Early erosions
- Failure of ≥2 csDMARDs
Combination therapy principles: bDMARDs and tsDMARDs should be combined with a csDMARD for optimal efficacy, though IL-6 inhibitors and JAK inhibitors may be used as monotherapy when csDMARDs cannot be used as comedication 1, 4.
The ACR 2021 guidelines conditionally recommend adding a bDMARD or tsDMARD over triple therapy (methotrexate + sulfasalazine + hydroxychloroquine) for patients with inadequate response to methotrexate, prioritizing faster improvement and better persistence 5.