Should Xeljanz (tofacitinib) be continued in a patient with rheumatoid arthritis who is already on it and in clinical remission?

Continuation of Xeljanz in Patients with Rheumatoid Arthritis in Clinical Remission

Xeljanz (tofacitinib) should be continued in patients with rheumatoid arthritis who are already on it and in clinical remission, as discontinuation significantly increases the risk of disease flare and may lead to difficulty in regaining disease control. 1

Rationale for Continuing Xeljanz in Clinical Remission

The 2020 EULAR recommendations for RA management provide clear guidance on this issue:

1. Maintaining Disease Control: RA is considered an incurable disease, and medications that have proven efficacy and are well-tolerated should not be stopped 1. Clinical remission represents optimal disease control, which is the primary treatment target in RA 1.

2. Risk of Flare After Discontinuation: Evidence shows that immediate withdrawal of tofacitinib leads to significantly higher rates of disease flare compared to dose reduction or continuation. The crude incidence rate of flares per person-year is 0.73 after withdrawal, compared to only 0.04 during continuation 2.

3. Time to Flare: Median flare-free time after tofacitinib withdrawal is only 7 months, compared to 21 months with dose reduction 2. This demonstrates the substantial risk of disease recurrence when the medication is stopped completely.

Tapering Approach vs. Complete Discontinuation

If dose adjustment is being considered due to sustained remission, the evidence supports a structured approach:

1. Tapering Sequence: The EULAR guidelines recommend that if tapering is considered, bDMARDs and tsDMARDs (like tofacitinib) should be tapered first before conventional synthetic DMARDs (Level of Evidence 1b, Strength of Recommendation A) 1.

2. Dose Reduction vs. Withdrawal: Dose reduction of tofacitinib is preferable to complete withdrawal, with significantly lower flare rates (0.44 vs. 0.73 per person-year) 2.

3. Persistent Remission Requirement: Any consideration of dose adjustment should only occur after persistent remission has been achieved for a significant period (expert opinion suggests at least 12 months) 1.

Safety Considerations for Long-term Use

While continuing Xeljanz, it's important to monitor for potential safety issues:

• Infection Risk: Tofacitinib carries a risk of serious infections comparable to most bDMARDs, though slightly higher than etanercept (aHR 1.41) 3.

• Herpes Zoster Risk: There is a 2-fold higher risk of herpes zoster with tofacitinib compared to bDMARDs, requiring vigilance 3.

• Regular Monitoring: Patients on continued tofacitinib therapy should have disease activity measures obtained and documented regularly (every 3-6 months for patients in sustained remission) 1.

Rescue Strategy if Flare Occurs

If a patient does experience a flare after any dose adjustment:

• Rapid Response to Reinitiation: Restart of the original treatment regimen leads to rapid remission in 93-100% of flare cases 2.

• Prompt Action: Early recognition and management of disease flares is essential to prevent joint damage and disability.

Conclusion

The evidence strongly supports continuing Xeljanz in patients with RA who have achieved clinical remission. While dose reduction may be considered in cases of persistent remission, complete withdrawal carries a substantial risk of disease flare. The treat-to-target principle emphasizes maintaining the desired treatment target (remission) throughout the remaining course of the disease 1.