SUMMARY: 

Vaccines have played a vital role in improving community health and life expectancy for the better part of the past century. Since the 1940s, vaccine development has expanded to cover a variety of infectious diseases, and has been proven to be safe and efficacious time and again. Despite many advances in vaccine technology, immunocompromised patients face the dual challenge of being both especially vulnerable to infectious diseases, and having less efficacy and safety profiles when vaccines are administered. The American College of Rheumatology has issued guidance on vaccine administration for rheumatic and musculoskeletal disease (RMD) patients. 

KEY POINTS: 

• The ACR notes that its recommendations are based on mostly low-quality evidence resulting in conditional recommendations  
  • Use of their recommendations should take into account: Risk of patient disease flare if immunosuppression is held | Risk for vaccine preventable illnesses | Risk of vaccine effects  
• Adult RMD patients on immunosuppressive medications should receive the following in addition to their regularly recommended vaccinations  
  • Quadrivalent (high dose) influenza vaccine (conditional recommendation)  
  • Recombinant zoster vaccine (Shingrix; strongly recommended)  
  • Pneumococcal vaccine (strongly recommended) 
• RMD patients on immunosuppressive medications who are > 26 and < 45 years old should receive HPV vaccine if not previously vaccinated (conditional recommendation) 
• RMD patients should receive all recommended non-live attenuated vaccines regardless of their disease activity AND immunosuppressive medications should be continued 
  • Exceptions to this in regard to specific medications and timing are outlined below 
• Live attenuated vaccines should be deferred for RMD patients on immunosuppressive medications (see below for further details)  
• Live attenuated vaccines include: MMR | Chickenpox | Rotavirus | Smallpox | Yellow fever  
• RMD patients may receive multiple vaccines on the same day  

MEDICATIONS AND VACCINE TIMING: 

Methotrexate (MTX) 

• Hold for two weeks after influenza vaccine is given if disease activity allows 
  • PCP can administer the flu vaccine and then contact patient’s rheumatologist for guidance on holding MTX 
• Methotrexate can be continued with all other non-live attenuated vaccinations  
• If live-attenuated vaccine is necessary, MTX should be held for 4 weeks before and after vaccination  
  • If the patient is taking methotrexate ≤ 0.4 mg/kg/week (low dose immunosuppression), then hold times can be shortened if vaccination is critical and the risk of a disease flare off immunosuppression is high  

Prednisone  

• Give all necessary non-live attenuated vaccines if total daily dose is ≤ 10 mg (strong recommendation) or > 10 to < 20 mg daily (conditional recommendation)  
• Give scheduled influenza vaccine regardless of prednisone dosing 
• Defer other non-live attenuated vaccines until prednisone can be tapered to < 20mg daily  
• Live attenuated vaccines can be given if prednisone is held for 4 weeks before and after vaccine is given  
  • Low dose prednisone (< 20 mg daily) can be continued if: Risk of disease flare is high | Risk of developing adrenal insufficiency is high | Vaccine is critical for patient’s health   

Rituximab  

• Give influenza vaccine on schedule and delay next rituximab dose for at least 2 weeks as disease activity allows 
• For all other non-live attenuated vaccines time them for when the next rituximab dose is due, and then hold rituximab for at least 2 weeks after vaccination  
• For live attenuated vaccines, hold rituximab for 6 months prior and 4 weeks after vaccine administration  

Leflunomide (Arava) | Mycophenolate mofetil (Cellcept) | Calcineurin inhibitors (e.g., Tacrolimus)  | Cyclophosphamide (PO) | Azathioprine (Imuran) 

• Hold these medicines for 4 weeks before and after live attenuated vaccines are given 
  • The exception is Azathioprine: if dose is ≤ 3 mg/kg/day (low dose immunosuppression), then hold times can be shortened if vaccination is critical and the risk of a disease flare off immunosuppression is high 

JAK inhibitors (e.g., Xeljanz, Jakafi, Olumiant)  

• Hold for 1 week prior and 4 weeks following administration of live attenuated vaccine  

TNF inhibitors (e.g. Remicade) | IL17 inhibitors | IL12/23 inhibitors |  IL23 inhibitors | BAFF/BLyS 
inhibitors | IL6 pathway inhibitors | IL1 inhibitors (e.g., Anakinra) | Abatacept | Anifrolumab | IV Cyclophosphamide  

• Hold these medicines for 1 dosing interval before and 4 weeks after live attenuated vaccines are given 
  • For medications with more than one FDA-approved dosing interval, the longest interval should be used 

IVIG 

• For dosing of 300-400 mg/kg: hold when giving a live attenuated vaccine for 8 months prior and 4 weeks after vaccine is given  
• For dosing of 1 gm/kg: hold when giving a live attenuated vaccine for 10 months prior and 4 weeks after vaccine is given 
• For dosing of 2 gm/kg: hold when giving a live attenuated vaccine for 11 months prior and 4 weeks after vaccine is given 
• The hold recommendations above are designed to enhance efficacy and not safety 
  • If vaccine is critically needed then the timeframes can be shortened  

Learn More – Primary Sources 

2022 American College of Rheumatology (ACR) Guideline for Vaccinations in Patients with Rheumatic and Musculoskeletal Diseases 

2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host 

CDC: General Best Practice Guidelines for Immunization: Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP)