How to initiate Disease-Modifying Antirheumatic Drugs (DMARDs) in patients with Rheumatoid Arthritis (RA)?

How to Start DMARDs in Rheumatoid Arthritis

Methotrexate should be initiated as the first-line DMARD as soon as RA is diagnosed, with rapid dose escalation to 20-25 mg weekly (or 16 mg in Asian populations), combined with folic acid supplementation. 1

Initial DMARD Selection

• Therapy with DMARDs should be started immediately after RA diagnosis to prevent joint damage and disability 1
• Methotrexate (MTX) should be part of the first treatment strategy in patients with active RA due to its established efficacy, safety profile, and role as an anchor drug 1, 2
• For patients with contraindications or early intolerance to MTX, consider leflunomide or sulfasalazine as alternative first-line options 1
• For patients with low disease activity, hydroxychloroquine is conditionally recommended over other csDMARDs 3, 2

Methotrexate Dosing and Administration

• Start with 7.5-10 mg weekly and rapidly escalate to 20-25 mg weekly (or 16 mg in Asian populations) within 4-6 weeks 1, 2, 4
• Consider subcutaneous administration if higher doses are needed or if gastrointestinal side effects occur, as it shows higher ACR20 response rates (85%) compared to oral administration (77%) 1, 4
• Always prescribe folic acid supplementation with MTX to reduce side effects 1, 2
• Patient education about MTX is crucial to address fears of potential side effects and improve adherence 1, 2

Treatment Strategy Based on Disease Activity

For Moderate to High Disease Activity:

• DMARD-naïve patients: Start MTX monotherapy with rapid dose escalation 1
• Add low-dose glucocorticoids (≤10 mg/day prednisone equivalent) as bridging therapy for up to 6 months while waiting for DMARD effect, then taper as rapidly as clinically feasible 1
• Monitor every 1-3 months; if no improvement by 3 months or target not reached by 6 months, adjust therapy 1

For Low Disease Activity:

• Consider hydroxychloroquine as first-line, followed by sulfasalazine, then MTX 3, 5
• Monitor less frequently than for moderate/high disease activity but still adjust therapy if target not reached 1

Treatment Escalation Algorithm

1. If inadequate response to MTX monotherapy after 3 months:

   • For patients with poor prognostic factors (RF/ACPA positivity, high disease activity, early joint damage, failure of 2 csDMARDs): Add a biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD) 1
   • For patients without poor prognostic factors: Add another csDMARD (leflunomide, sulfasalazine, hydroxychloroquine) or switch to another csDMARD strategy 1

2. If inadequate response to combination csDMARDs after 3 months:

   • Add or switch to a bDMARD (preferably TNF inhibitor) combined with MTX 1

3. If inadequate response to first bDMARD after 3-6 months:

   • Switch to another bDMARD (same or different class) or tsDMARD 1

Special Populations and Considerations

• Serious infection within previous 12 months: Addition of/switching to DMARDs is conditionally recommended over initiation/dose escalation of glucocorticoids 1
• Nontuberculous mycobacterial lung disease: Add csDMARDs over bDMARDs/tsDMARDs; if bDMARDs needed, abatacept is conditionally recommended over other options 1
• Heart failure (NYHA class III or IV): Use non-TNF inhibitor bDMARDs or tsDMARDs instead of TNF inhibitors 1
• Previous lymphoproliferative disorder: Rituximab is conditionally recommended over other DMARDs 1
• Hepatitis B infection: Prophylactic antiviral therapy is strongly recommended when initiating rituximab or other b/tsDMARDs in hepatitis B core antibody positive patients 1

Common Pitfalls to Avoid

• Delaying DMARD therapy beyond 3 months after symptom onset significantly reduces the chance of optimal outcomes 5
• Using long-term glucocorticoids instead of appropriate DMARD therapy increases risk of significant toxicity without addressing the underlying disease process 5
• Starting with inadequate MTX dosing (too low) or failing to escalate to optimal doses 2, 4
• Initiating biologic DMARDs before optimizing MTX therapy in DMARD-naïve patients 3, 2
• Neglecting folic acid supplementation with MTX, leading to unnecessary side effects 1, 2
• Failing to monitor disease activity regularly and adjust therapy accordingly 1