Does having rheumatoid arthritis (RA) and taking methotrexate (MTX) and hydroxychloroquine (HCQ) put you in a moderately or severely immune-compromised state?

Immune Status in Rheumatoid Arthritis Patients on Methotrexate and Hydroxychloroquine

Patients with rheumatoid arthritis taking methotrexate and hydroxychloroquine are considered moderately immunocompromised, not severely immunocompromised. This classification has important implications for vaccination strategies, infection risk management, and overall clinical care.

Understanding Immunosuppression Categories in RA

Moderate Immunosuppression

Patients taking the following medications fall into the moderately immunocompromised category:

• Methotrexate (MTX) at standard rheumatologic doses (typically 7.5-25mg weekly)
• Hydroxychloroquine (HCQ)
• Combination therapy with MTX and HCQ

The American College of Rheumatology (ACR) and Infectious Diseases Society of America (IDSA) guidelines classify these conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) as causing moderate immunosuppression 1.

Severe Immunosuppression

This category typically includes:

• High-dose corticosteroids (>20mg prednisone daily for ≥2 weeks)
• Biologic DMARDs (TNF inhibitors, rituximab, etc.)
• Combination of multiple immunosuppressive agents including biologics
• Patients with additional immunocompromising conditions

Clinical Implications of Moderate Immunosuppression

Infection Risk

• Moderately increased risk of common and opportunistic infections
• Not as high risk as severely immunocompromised patients
• MTX and HCQ combination has a more favorable safety profile compared to triple therapy or biologics 1

Vaccination Recommendations

The 2022 ACR vaccination guidelines provide specific recommendations for moderately immunocompromised patients 1:

1. Pneumococcal vaccination is strongly recommended for patients with RA taking immunosuppressive medications
2. Recombinant zoster vaccine (not live) is strongly recommended for patients >18 years on immunosuppressive therapy
3. Influenza vaccination should be administered annually
4. Methotrexate considerations: Holding MTX for 2 weeks after influenza vaccination is conditionally recommended to improve vaccine response, if disease activity allows
5. Hydroxychloroquine: Generally does not require modification around vaccination time

Tuberculosis Screening

Patients on MTX and HCQ should undergo TB screening before initiating therapy, but the risk of TB reactivation is lower compared to biologic agents 1.

Management Considerations

Medication Monitoring

• Regular monitoring of complete blood count, liver function, and renal function is essential for patients on MTX 1
• Less intensive monitoring is needed for HCQ (primarily ophthalmologic)
• The combination of MTX and HCQ is considered to have an acceptable safety profile for long-term use 1

Risk Stratification

When assessing infection risk or planning procedures:

• Patients on MTX + HCQ without other risk factors should be considered moderately immunocompromised
• Additional factors that may increase risk include:
  • Age >65 years
  • Comorbidities (diabetes, COPD, chronic kidney disease)
  • High disease activity
  • Concomitant corticosteroid use

Common Pitfalls to Avoid

1. Overestimating immunosuppression: Unnecessarily restricting activities or treatments based on incorrect classification as severely immunocompromised
2. Underestimating immunosuppression: Failing to provide appropriate vaccinations or infection prophylaxis
3. Medication discontinuation: Inappropriately stopping MTX or HCQ during minor infections or procedures
4. Vaccination timing: Not optimizing vaccination timing in relation to MTX administration (consider holding MTX for 2 weeks after influenza vaccination)
5. Overlooking drug interactions: Not accounting for potential interactions between MTX, HCQ and other medications

Conclusion

The combination of methotrexate and hydroxychloroquine for rheumatoid arthritis places patients in a moderately immunocompromised state, not a severely immunocompromised one. This distinction is important for appropriate clinical management, vaccination strategies, and patient counseling regarding infection risks.