Methotrexate Management for Flu Vaccination in Rheumatic Disease Patients
For patients with rheumatic and musculoskeletal diseases, methotrexate should be held for 2 weeks after influenza vaccination if disease activity allows, to maximize vaccine immunogenicity. 1
Evidence-Based Recommendation
The 2022 American College of Rheumatology (ACR) guidelines provide clear direction on this clinical question. The guidelines specifically recommend:
- Hold methotrexate for 2 weeks after influenza vaccination if disease activity allows 1
- Continue methotrexate for other non-influenza vaccinations 1
Rationale for Temporarily Discontinuing Methotrexate
Multiple studies demonstrate that methotrexate significantly blunts the immunogenicity of influenza vaccination:
- Observational studies show methotrexate reduces but doesn't completely eliminate vaccine response 1
- Randomized controlled trials confirm that temporary discontinuation improves vaccine immunogenicity 2, 3
Implementation Algorithm
Before vaccination:
- Assess current rheumatic disease activity
- Determine if disease is stable enough to tolerate a 2-week methotrexate hold
- Discuss with patient the benefits of improved vaccine response versus risk of disease flare
At vaccination:
- Administer influenza vaccine as scheduled
- Hold methotrexate for 2 weeks after vaccination
- If non-rheumatology provider is administering the vaccine, they should give the vaccination and then consult with rheumatology about holding methotrexate 1
After vaccination:
- Resume methotrexate after 2 weeks
- Monitor for disease flares
Duration of Methotrexate Hold
Research evidence supports that a 2-week discontinuation is optimal:
- A 2-week hold after vaccination significantly improves vaccine response (75.5% vs 54.5% satisfactory response) 2
- Shorter holds (1-week) may be sufficient but have less robust evidence 4
- Longer holds (4-week) increase risk of disease flares without additional immunologic benefit 5, 3
Important Considerations and Caveats
- Disease activity is paramount: Only hold methotrexate if disease activity allows 1
- Risk of flare: Short-term (2-week) discontinuation appears safe, but 4-week discontinuation is associated with increased flare risk (20.5% vs 7.4%) 5
- Timing matters: The evidence specifically supports holding methotrexate after vaccination, not before 2, 3
- Non-influenza vaccines: Continue methotrexate for all other non-live attenuated vaccines 1
Special Situations
- For patients with highly active disease where a flare would be particularly concerning, continuing methotrexate may be preferable to risking disease destabilization
- For patients receiving rituximab, timing of influenza vaccination is more important than methotrexate management 1
- For patients on high-dose glucocorticoids (≥20mg prednisone daily), the impact of methotrexate hold may be less significant as glucocorticoids themselves substantially reduce vaccine response 1