Are steroids considered Disease-Modifying Antirheumatic Drugs (DMARDs)?

Are Steroids Considered DMARDs?

Glucocorticoids (steroids) are not traditionally classified as DMARDs in the formal nomenclature, but they do possess disease-modifying properties in rheumatoid arthritis when used at low doses, particularly in early disease. 1, 2

Formal Classification of DMARDs

The established DMARD classification system divides these agents into three categories 1, 3:

• Conventional synthetic DMARDs (csDMARDs): methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, azathioprine 1, 3
• Biologic DMARDs (bDMARDs): TNF inhibitors, IL-6 inhibitors, B-cell depleting agents, T-cell costimulation blockers 1, 4
• Targeted synthetic DMARDs (tsDMARDs): JAK inhibitors and other small molecules specifically designed to target molecular structures 1, 3

Glucocorticoids are conspicuously absent from this formal classification system. 1

Evidence for Disease-Modifying Properties

Despite their exclusion from formal nomenclature, substantial evidence demonstrates that low-dose glucocorticoids can retard radiographic progression in rheumatoid arthritis 4, 2:

• Short-term efficacy: Systemic glucocorticoids—either alone or combined with DMARDs—effectively relieve signs and symptoms in early and established RA 4
• Radiographic benefits: Multiple RCTs show that low-dose prednisone (≤10 mg/day) can slow joint damage progression when combined with conventional DMARDs 4, 2
• Early disease: The disease-modifying effect is especially prominent in early RA and when used in combination with other drugs 2

However, this evidence is not uniformly positive. Some trials failed to demonstrate radiographic benefits, and subanalyses of newer DMARD trials showed no added benefit of low-dose prednisone on radiographic progression 4.

Clinical Practice Guidelines Position

Current guidelines treat glucocorticoids as adjunctive therapy rather than primary DMARDs 4, 3, 5:

• Bridging therapy: Low-dose glucocorticoids (≤10 mg/day prednisone equivalent) should be added as temporary bridging therapy for up to 6 months while awaiting DMARD effect, then tapered as rapidly as clinically feasible 3, 5
• Not first-line: Methotrexate remains the anchor drug and first-line DMARD; glucocorticoids are never recommended as monotherapy for disease modification 4, 3
• Temporary use only: Guidelines emphasize temporary use (<6 months) at the lowest effective dose due to cumulative toxicity including weight gain, hypertension, diabetes, cataracts, and osteoporosis 4, 5

Key Distinctions from True DMARDs

Glucocorticoids differ from conventional DMARDs in critical ways 4, 6:

• Safety profile: Long-term safety of low-dose glucocorticoids remains largely unknown, whereas established DMARDs have well-characterized long-term toxicity profiles 4
• Sustainability: DMARDs are intended for long-term disease control; glucocorticoids are explicitly temporary 4, 5
• Mechanism: True DMARDs modify the underlying disease process through specific immunomodulation, while glucocorticoids provide broad anti-inflammatory effects 6

Practical Clinical Algorithm

When managing rheumatoid arthritis 3, 5:

1. Start with a csDMARD (methotrexate preferred) as the disease-modifying agent
2. Add low-dose glucocorticoids (≤10 mg/day prednisone) as bridging therapy if needed for symptom control
3. Taper glucocorticoids within 3-6 months as the DMARD takes effect
4. Never use glucocorticoids alone as the primary disease-modifying strategy
5. If inadequate response at 3-6 months, escalate to biologic or targeted synthetic DMARDs—not higher-dose or prolonged glucocorticoids 3, 5

Common Pitfalls

• Avoiding the trap of chronic steroid use: Glucocorticoids should never become long-term maintenance therapy; failure to taper indicates inadequate DMARD therapy requiring escalation 5
• Misunderstanding their role: While glucocorticoids may slow radiographic progression, they are adjunctive agents, not replacements for true DMARDs 4, 2
• Overlooking monitoring requirements: When used, glucocorticoids require careful monitoring and appropriate prevention strategies for osteoporosis and other complications 4