What is the recommended approach for tapering methotrexate (disease-modifying antirheumatic drug, DMARD)?

Methotrexate Tapering in Rheumatoid Arthritis

When tapering methotrexate in patients with rheumatoid arthritis, gradual dose reduction is conditionally recommended over abrupt discontinuation, and patients should be at target (low disease activity or remission) for at least 6 months before considering any tapering. 1

Prerequisites for Tapering

Before considering methotrexate tapering:

• Patient must achieve target (low disease activity or remission) for at least 6 months 1, 2
• Glucocorticoids should be tapered and discontinued first 1
• If on combination therapy with biologics, consider tapering biologics before methotrexate 1

Tapering Algorithm

1. Initial Assessment:

   • Confirm sustained low disease activity or remission for ≥6 months
   • Ensure all glucocorticoids have been discontinued
   • Assess patient's risk factors for flare

2. Tapering Approach:

   • First option: Continue methotrexate at current dose if possible 1
   • If tapering desired: Implement gradual dose reduction rather than discontinuation 1
   • If discontinuation necessary: Use gradual tapering rather than abrupt cessation 1

3. Practical Tapering Method:

   • Reduce dose by 2.5-5 mg every 8-12 weeks 3
   • Monitor disease activity at each dose reduction
   • Maintain the reduced dose for 2-3 months before further reduction 2
   • For subcutaneous methotrexate, consider extending the interval between doses rather than reducing the dose 3

4. Combination Therapy Considerations:

   • If on methotrexate plus biologic/tsDMARD: Methotrexate should be gradually discontinued before the biologic/tsDMARD if discontinuation is desired 1
   • For triple therapy: Consider discontinuing sulfasalazine before hydroxychloroquine 1

Monitoring During Tapering

• Clinical assessment every 1-3 months during tapering 2
• Laboratory monitoring (CBC, liver function, renal function) at each dose change
• Disease activity measures (joint counts, inflammatory markers, patient-reported outcomes)
• Prompt assessment if symptoms of flare occur

Managing Flares

• If disease activity increases, return to the previous effective dose 3
• Consider resuming the original dose if significant flare occurs
• Reassess disease activity 4-8 weeks after dose adjustment

Important Caveats

• Tapering carries approximately 10% reduction in ability to sustain remission 4
• Complete discontinuation of all DMARDs has high risk of flare (up to 67% in some studies) 1
• Patients with early disease, seronegative status, and longer duration of remission may have better outcomes with tapering
• Radiographic progression may occur even with clinical remission, requiring careful monitoring

Special Situations

• In patients with subcutaneous nodules, consider switching to non-methotrexate DMARD if nodules are progressive 1
• For patients with mild, stable lung disease, methotrexate can generally be continued with appropriate monitoring 1, 2
• If planning pregnancy, methotrexate must be discontinued at least 3 months before conception 2

The evidence for specific tapering protocols is limited, but the principle of gradual reduction with careful monitoring is supported by clinical guidelines and expert opinion. The decision to taper should always balance the benefits of reduced medication burden against the risk of disease flare.