Should methotrexate, sulfasalazine, and hydroxychloroquine be temporarily stopped in a patient with rheumatoid arthritis who develops an acute infection?

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Last updated: October 26, 2026 • View editorial policy

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Management of DMARDs During Acute Infection in Rheumatoid Arthritis

For patients with rheumatoid arthritis who develop an acute infection, methotrexate and sulfasalazine should be temporarily stopped, while hydroxychloroquine may be continued.

Evidence-Based Approach

The most recent and authoritative guidance comes from the 2020 ACR COVID-19 guidance 1, which provides specific recommendations for managing DMARDs during acute infections. While this guidance was developed for COVID-19, it represents the most current expert consensus on infection management and has been widely applied to general acute infections in clinical practice.

Specific Medication Management

Hydroxychloroquine (HCQ):

  • May be continued during acute infection 1
  • Has minimal immunosuppressive effects and does not significantly increase infection risk
  • The 2023 EULAR recommendations specifically exempt HCQ from the category of immunosuppressive csDMARDs due to its mild immunomodulatory effect 2

Sulfasalazine (SSZ):

  • Should be stopped during documented or presumptive acute infection 1
  • Moderate to high consensus supports discontinuation
  • Can be restarted 7-14 days after symptom resolution for uncomplicated infections

Methotrexate (MTX):

  • Should be stopped or withheld during acute infection 1
  • High consensus (moderate to high level) supports temporary discontinuation
  • The FDA label warns about increased infection risk and recommends caution with any signs of infection 3

Severity-Based Decision Making

For serious infections (requiring IV antibiotics or hospitalization):

  • All three medications should be held
  • The 2021 ACR guidelines define serious infection as requiring intravenous antibiotics or hospitalization 4
  • This represents a clear threshold for mandatory discontinuation

For mild-to-moderate infections:

  • HCQ may continue
  • MTX and SSZ should be temporarily stopped
  • Clinical judgment regarding infection severity guides timing of restart

Restarting Treatment

Uncomplicated infections:

  • Consider restarting DMARDs within 7-14 days of symptom resolution 1
  • This applies to infections treated in ambulatory settings or via self-quarantine

More severe infections:

  • Decisions should be made on a case-by-case basis 1
  • Consider infection severity, patient comorbidities, and RA disease activity

Important Clinical Considerations

Common Pitfalls to Avoid

  1. Don't continue all DMARDs uniformly - The immunosuppressive profiles differ significantly between these three medications
  2. Don't delay stopping MTX/SSZ - Early discontinuation at first sign of serious infection is critical
  3. Don't restart too early - Wait for complete symptom resolution plus the appropriate observation period

Monitoring During Infection

  • Assess infection severity promptly
  • Monitor for signs of worsening infection
  • Consider RA disease activity when planning restart timing
  • Balance infection risk against RA flare risk

Drug-Specific Safety Profiles

The FDA labels highlight different infection concerns:

  • Methotrexate: Associated with serious infections including fatal sepsis and pneumonia; can cause immunosuppression 3
  • Sulfasalazine: Serious infections including fatal sepsis reported; associated with blood dyscrasias that increase infection risk 5
  • Hydroxychloroquine: Not specifically highlighted for infection risk in the same manner

Practical Algorithm

  1. Identify acute infection → Assess severity
  2. Serious infection present?
    • Yes → Stop MTX and SSZ immediately; may continue HCQ
    • No → Consider stopping MTX and SSZ; continue HCQ
  3. Monitor infection course → Treat infection appropriately
  4. Infection resolved?
    • Uncomplicated: Wait 7-14 days after symptom resolution
    • Complicated: Individualize timing based on clinical status
  5. Restart DMARDs → Resume MTX and SSZ; HCQ continues if not stopped

This approach prioritizes patient safety by reducing immunosuppression during active infection while recognizing that HCQ has a fundamentally different risk profile that allows continuation in most circumstances 1, 2.

References

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.