What is the recommended approach for tapering Disease-Modifying Antirheumatic Drugs (DMARDs) in patients with seronegative Rheumatoid Arthritis (RA)?

Tapering DMARDs in Seronegative Rheumatoid Arthritis

For patients with seronegative rheumatoid arthritis, tapering of DMARDs should only be considered after achieving low disease activity or remission for at least 6 months, with biologics tapered first followed by cautious reduction of conventional synthetic DMARDs if sustained remission continues. 1

Prerequisites for DMARD Tapering

• Patients must be in persistent low disease activity or remission for at least 6 months before considering any tapering strategy 1
• Disease activity should be measured using validated instruments such as DAS28 or SDAI to confirm stable disease control 1
• Tapering should be implemented as part of a treat-to-target approach with frequent monitoring 1

Recommended Tapering Sequence

Step 1: Glucocorticoid Tapering

• If the patient is on glucocorticoids, these should be tapered first before considering DMARD tapering 1
• Glucocorticoids should be tapered as rapidly as clinically feasible to minimize long-term adverse effects 1
• Caution: Some patients may require continued low-dose glucocorticoids (5mg prednisone) for disease control even with DMARDs 2

Step 2: Biologic DMARD Tapering

• After glucocorticoid tapering and with maintained disease control, consider tapering biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) first 1, 3
• Recommended approach for bDMARD tapering:
  • Begin with dose reduction (lowering dose or increasing dosing interval) rather than abrupt discontinuation 1
  • A 33% dose reduction appears practical and has minimal impact on disease flares compared to 66% reduction, which significantly increases flare risk 3
  • TNF inhibitors can be effectively tapered in approximately 30% of patients with stable low disease activity 4

Step 3: Conventional Synthetic DMARD Tapering

• Only consider tapering conventional synthetic DMARDs (csDMARDs) after successful tapering of biologics and with continued remission 1
• csDMARD tapering should be more cautious and implemented as a shared decision between patient and physician 1
• Maintain methotrexate if possible, as concomitant methotrexate is positively associated with successful biologic tapering 4

Monitoring During Tapering

• Disease activity should be monitored frequently during tapering (every 1-3 months) 1
• Define flare criteria in advance (e.g., increase in DAS28 ≥0.6 with at least one additional swollen joint) 3
• Be prepared to promptly reinstate previous effective doses if disease activity increases 5

Risk Factors for Flare During Tapering

• Higher baseline pain scores and elevated ESR are associated with increased risk of relapse during tapering 5
• Patients without concomitant methotrexate have higher risk of flare during biologic tapering 4
• More aggressive tapering (66% dose reduction vs. 33%) significantly increases flare risk 3

Important Considerations and Pitfalls

• Approximately 15% of patients may not respond to reinstatement of full-dose biologics after a flare, highlighting the importance of cautious tapering 5
• The presence of radiographic damage should be considered when making tapering decisions 1
• Seronegative status itself is not specifically addressed in guidelines for tapering, so standard RA tapering principles apply 1
• Tapering should always be implemented as a shared decision with the patient, with clear discussion of potential benefits and risks 1

Long-term Outcomes

• With careful tapering, approximately 65% of patients can successfully maintain low disease activity with reduced doses 5
• Long-term follow-up shows that relapse rates are approximately 10% at 6 months, 19% at 12 months, and 50% after 5 years of dose reduction 5
• Mean duration of successful dose reduction can be approximately 4.5 years in well-selected patients 5