When can a COVID-19 (Coronavirus Disease 2019) vaccine be administered after a patient receives a dose of rituximab (Rituxan, generic name: rituximab)?

COVID-19 Vaccination Timing After Rituximab

COVID-19 vaccination should be administered at least 6 months after the last dose of rituximab to optimize vaccine response, though 9 months may be preferable for maximal immunogenicity. 1

Guideline-Based Recommendations

Standard Timing Interval

• Delay vaccination for at least 6 months after the last rituximab dose for patients with end-stage renal disease (ESRD), neurologic disorders including multiple sclerosis, and other conditions requiring immunosuppressive therapy 1

• Patients receiving immune reconstitution therapy (IRT), including rituximab, should be vaccinated 6 months after treatment across both mRNA and adenoviral vector vaccine platforms 1

• If active underlying disease is present, immunosuppressive therapy (including rituximab) should be prioritized over vaccination until the condition is stabilized 1

Alternative Approach: Delaying Rituximab After Vaccination

The American College of Rheumatology provides an inverse strategy when vaccination timing is prioritized:

• Delay the next rituximab dose by 2-4 weeks after the second COVID-19 vaccine dose if disease activity allows 1

• This approach assumes the patient receives vaccination first, then adjusts rituximab timing to optimize vaccine response 1

Evidence-Based Refinements

The 9-Month Interval May Be Superior

Recent research suggests the standard 6-month recommendation may be insufficient:

• Only 17.3% of patients developed detectable antibodies when vaccinated ≤6 months after rituximab, compared to 66.7% at 9-12 months 2

• A 9-month rituximab-to-vaccination interval coincides with naïve B lymphocyte repopulation and maximizes immunological benefits while avoiding unnecessary treatment delays 3

• Patients vaccinated >6 months after rituximab had significantly reduced COVID-19 hospitalization risk (adjusted OR 0.22) compared to those vaccinated ≤6 months after treatment 4

Critical Factors Affecting Response

B-cell recovery status is the key determinant:

• Patients with undetectable CD20+ cell levels do not seroconvert regardless of vaccination timing 5

• Hypogammaglobulinemia is associated with a 15-fold decrease in seroconversion likelihood 5

• Only 36% of patients who failed to respond after the primary vaccine series achieved seroconversion with a supplemental dose 5

Clinical Algorithm

For patients currently on rituximab:

1. Check CD20+ B-cell levels and immunoglobulin levels before vaccination 5
2. If CD20+ cells are detectable and immunoglobulins are adequate, vaccinate at 6-9 months after the last rituximab dose 1, 2, 3
3. If CD20+ cells remain undetectable at 6 months, delay vaccination further until B-cell recovery is documented 5

For patients planning to start rituximab:

1. Complete the COVID-19 vaccine series before initiating rituximab whenever possible 1
2. If rituximab cannot be delayed, administer at least the first vaccine dose, then delay rituximab by 2-4 weeks after the second dose 1

Special Considerations

Vaccine Type Matters

• mRNA vaccines (Pfizer/Moderna) are independently associated with decreased COVID-19 hospitalization risk (adjusted OR 0.36) in rituximab-treated patients 4

• Booster doses provide additional protection (adjusted OR 0.31 for hospitalization) and should be strongly encouraged 4

Prior COVID-19 Infection

• Patients with documented prior SARS-CoV-2 infection may develop adequate antibody responses even with shorter rituximab-to-vaccine intervals (<6 months), as natural infection creates memory B cells that can be reactivated by vaccination 6

• This finding suggests some flexibility in timing for patients with confirmed prior infection 6

Common Pitfalls to Avoid

• Do not assume the 6-month interval is sufficient for all patients—consider extending to 9 months for optimal response, particularly in those with severe disease requiring robust immunity 2, 3

• Do not vaccinate patients with persistently undetectable B cells—this will likely result in vaccine failure 5

• Do not delay rituximab indefinitely in patients with active disease—the absolute risk of COVID-19 hospitalization remains low even with suboptimal vaccine response, and disease control takes priority 4

• Do not forget booster doses—rituximab-treated patients benefit significantly from additional vaccine doses 4

• Consider monoclonal antibody prophylaxis for high-risk patients who cannot mount adequate vaccine responses 5