What are the recommended vaccine doses and booster schedules for immunocompromised Systemic Lupus Erythematosus (SLE)/Rheumatoid Arthritis (RA) patients?

Vaccination Schedules for Immunocompromised SLE/RA Patients

Immunocompromised SLE and RA patients should receive both PCV13 followed by PPSV23 for pneumococcal protection, annual inactivated influenza vaccines, and recombinant zoster vaccine (Shingrix) after age 50, with specific timing modifications based on their immunosuppressive regimen. 1

Pneumococcal Vaccination Schedule

For Vaccine-Naïve Patients

• Administer PCV13 first, followed by PPSV23 at least 8 weeks later 1
• Give a second PPSV23 dose 5 years after the first PPSV23 1
• Administer a third PPSV23 dose at age 65 or later, provided at least 5 years have elapsed since the last PPSV23 1

For Previously Vaccinated Patients

• If received PPSV23 only: Give PCV13 at least 1 year after the most recent PPSV23, then give second PPSV23 at least 5 years after first PPSV23 and at least 8 weeks after PCV13 1
• If received PCV13 only: Give PPSV23 at least 8 weeks after PCV13, then second PPSV23 5 years later 1
• If received both vaccines: Give second PPSV23 at least 5 years after first PPSV23 and at least 8 weeks after PCV13 1

Important caveat: While this sequential strategy is recommended by CDC/ACIP guidelines, immunogenicity may be suboptimal in SLE/RA patients on immunosuppression, with fewer than 40% achieving adequate immune responses in some studies 1. Methotrexate and TNF inhibitors particularly reduce vaccine immunogenicity 1.

Influenza Vaccination

• Annual quadrivalent inactivated influenza vaccine for all SLE/RA patients 1, 2
• For patients ≥65 years or all immunocompromised patients, use high-dose or adjuvanted formulations 1, 2
• Live attenuated influenza vaccines are absolutely contraindicated 1

Medication Management Around Influenza Vaccination

• Methotrexate: Hold for 2 weeks after vaccination if disease activity permits 1, 2
• TNF inhibitors, IL-6, IL-17, IL-1 inhibitors: Continue without interruption 1, 2
• JAK inhibitors: Hold for 1 week after vaccination 1
• Rituximab: Vaccinate as long as possible after last dose (ideally ≥6 months) and 4 weeks before next dose 1

Herpes Zoster Vaccination

• Recombinant zoster vaccine (Shingrix/RZV) is the only appropriate option for immunocompromised SLE/RA patients aged ≥50 years 1, 3
• Two doses given 2-6 months apart 3
• Live zoster vaccine (Zostavax) is absolutely contraindicated in patients on immunosuppression 1, 3

Optimal Timing Strategy

• Ideally administer both RZV doses before starting biologic DMARDs or JAK inhibitors 1, 3
• If already on immunosuppression, proceed without delay—do not defer vaccination 3
• For patients on JAK inhibitors: hold medication for 1 week after each dose 1
• For patients on biologics: hold for one dosing interval before vaccination and 4 weeks after 1

Other Recommended Vaccines

Hepatitis B

• Vaccinate all nonimmune adults at risk for HBV infection 1
• Standard 3-dose series, though immune response may be attenuated 1

Human Papillomavirus (HPV)

• Follow general population guidelines, with particular emphasis in SLE patients due to increased HPV infection risk 1, 4
• Safe and immunogenic in autoimmune disease patients 4

Tetanus-Diphtheria-Pertussis

• Follow standard adult schedules 1
• Consider particularly for rituximab-treated patients 1

Glucocorticoid Dose Considerations

The glucocorticoid dose significantly impacts vaccination timing for non-influenza vaccines:

• Prednisone ≤10 mg/day: Give all vaccines without restriction 1, 2
• Prednisone >10 mg but <20 mg/day: Give all vaccines (conditional recommendation) 1, 2
• Prednisone ≥20 mg/day: Give influenza vaccine, but defer other non-live vaccines until dose reduced to <20 mg/day 1

This stratification aims to maximize vaccine efficacy while recognizing that some patients cannot delay vaccination (e.g., children requiring vaccines for school entry) 1.

Disease Activity Considerations

Vaccinate regardless of disease activity level for non-live vaccines 1. While one study showed lower seroconversion in pediatric lupus patients with high disease activity (SLEDAI >8), most evidence does not support deferring vaccination based on disease activity 1. However, shared decision-making is critical as patients often express concerns about vaccine-induced flares, though prospective studies have not demonstrated increased flare rates 1.

Critical Medication-Specific Modifications for All Non-Live Vaccines

Rituximab (Most Significant Impact)

• Hold for 6 months before vaccination, then vaccinate 4 weeks before next dose 1
• Rituximab profoundly impairs both T-cell-dependent and T-cell-independent vaccine responses 1

Methotrexate

• For influenza only: Hold 2 weeks after vaccination 1, 2
• For all other non-live vaccines: Continue without interruption 2

Mycophenolate Mofetil and JAK Inhibitors

• Hold for 1 week after each vaccine dose 1

Abatacept

• Subcutaneous: Hold 1 week before and 1 week after first dose only 1
• Intravenous: Time first dose 4 weeks after abatacept, postpone next infusion by 1 week 1

Cyclophosphamide

• Time cyclophosphamide 1 week after each vaccine dose 1

No Modification Required

• TNF inhibitors, IL-6R inhibitors, IL-1 inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, belimumab, azathioprine, sulfasalazine, leflunomide, hydroxychloroquine, apremilast 1, 2

Live Vaccine Contraindications

Live attenuated vaccines are contraindicated in SLE/RA patients on immunosuppression 1. If live vaccines are absolutely necessary (e.g., outbreak situations), immunosuppressive medications must be held for appropriate periods:

• Glucocorticoids, methotrexate, azathioprine, leflunomide, mycophenolate, calcineurin inhibitors, oral cyclophosphamide: Hold 4 weeks before and 4 weeks after 1
• JAK inhibitors: Hold 1 week before and 4 weeks after 1
• Most biologics: Hold 1 dosing interval before and 4 weeks after 1
• Rituximab: Hold 6 months before and 4 weeks after 1

However, the safer approach is to use inactivated alternatives whenever available (e.g., inactivated influenza instead of live attenuated) 1.