If a patient is not immune to hepatitis B, should they complete the hepatitis B vaccination series before initiating Stellara (ustekinumab)?

Should Hepatitis B Vaccination Be Completed Before Starting Stellara?

Yes, patients who are not immune to hepatitis B should ideally complete the hepatitis B vaccination series before initiating Stellara (ustekinumab), though this should not delay necessary treatment if the clinical situation is urgent.

Rationale and Evidence

The most recent and relevant guideline for patients starting immunosuppressive therapy comes from the 2025 AGA Clinical Practice Update on IBD patients 1. This guideline explicitly states that universal hepatitis B vaccination is recommended for all adults starting immune-modifying therapy 1. While this guideline specifically addresses IBD patients, the principle applies directly to Stellara (ustekinumab), which is an immunomodulator used for both IBD and psoriasis.

Key Considerations:

Hepatitis B Reactivation Risk:

• Patients with IBD on immunosuppressive therapy face increased risk of HBV reactivation, which can lead to death in approximately 5% of cases 1
• Recent meta-analysis data shows HBV reactivation occurs in 10% of HBsAg-positive patients on ustekinumab, though this risk appears lower than with other biologics 2

Vaccination Response on Immunosuppression:

• Immunosuppressive medications significantly impair vaccine response
• Meta-analysis demonstrates that immunomodulators reduce adequate immune response by 27% (RR: 0.73) and anti-TNFs by 28% (RR: 0.72) compared to no immunosuppression 3
• Vaccination should preferably be done before starting immunosuppressive drugs to maximize seroconversion rates 3

Practical Algorithm:

For Non-Immune Patients:

1. Check HBV serologies (HBsAg, anti-HBs, anti-HBc) before starting Stellara 1

2. If patient is seronegative (not immune):

   • Initiate HBV vaccination series immediately
   • Use HEPLISAV-B (2-dose series at 0 and 1 month) for faster completion 1
   • Alternative: Standard 3-dose series (0,1, and 6 months) with Engerix-B or Recombivax HB 1

3. Timing of Stellara initiation:

   • Ideal scenario: Complete vaccination series before starting Stellara
   • If treatment cannot be delayed: Start first vaccine dose immediately and proceed with Stellara, continuing vaccination series as scheduled
   • The vaccine can be given concurrently with immunosuppressive therapy, though response may be suboptimal 1

4. Post-vaccination monitoring:

   • Check anti-HBs levels 4-8 weeks after final dose 1
   • If anti-HBs <10 mIU/mL (non-responder), give single challenge dose and recheck 1
   • If still no response, complete second full vaccination series 1

Important Caveats:

Do not delay urgent treatment for severe disease to complete vaccination. The clinical urgency of starting Stellara must be weighed against the benefit of completing vaccination first. For moderate-to-severe disease requiring immediate treatment, initiate vaccination and Stellara simultaneously.

Age matters: Patients younger than 26 years have significantly better vaccine response (OR: 6.01) 4, so timing may be less critical in younger patients who can mount adequate responses even on therapy.

Previous vaccination history: If the patient previously completed a vaccination series but is now anti-HBs negative, they likely have immune memory and may respond to a single booster dose rather than requiring the full series 1.

The 2018 ACIP guidelines support this approach, emphasizing that vaccination of susceptible persons should not be delayed, but optimal protection is achieved when vaccination precedes immunosuppression 5.