Does Abatacept (abatacept) increase the risk of shingles episodes in vaccinated patients?

Abatacept and Shingles Risk in Vaccinated Patients

Yes, abatacept increases the risk of shingles episodes even in vaccinated patients, though the absolute risk remains moderate at approximately 4.6% over several years of treatment. 1

Understanding the Baseline Risk

• Patients with autoimmune inflammatory rheumatic diseases (AIIRD) already have an elevated baseline risk of herpes zoster compared to the general population, independent of treatment 1
• Abatacept specifically confers a moderate risk of herpes zoster reactivation, with data showing 46 per 1,000 patients (4.6%) developing reactivation over follow-up periods ranging from 24 to 154 months 1
• This risk exists because abatacept is an anti-T-cell therapy that modulates T-cell costimulation, and cell-mediated T-cell immunity is the primary defense mechanism against varicella zoster virus reactivation 1

Why Vaccination May Not Fully Protect

The critical issue is that vaccine immunogenicity data for patients currently taking abatacept have not been reported 1. This creates several clinical challenges:

• We lack direct evidence on how well either the live zoster vaccine (Zostavax) or recombinant zoster vaccine (Shingrix) work in patients actively taking abatacept 1
• Cell-mediated VZV-specific T-cell responses correlate more strongly with protection against future shingles than antibody levels alone 1
• Since abatacept directly affects T-cell function, it may theoretically blunt the vaccine response even with the more immunogenic recombinant vaccine 1

Vaccination Strategy for Abatacept Patients

The recombinant zoster vaccine (Shingrix) should be strongly considered before initiating abatacept therapy whenever possible 1:

• For patients ≥50 years old, administer the 2-dose Shingrix series ideally before starting abatacept 1, 2
• The recombinant vaccine is non-live and safe in immunocompromised patients, unlike the live vaccine which carries theoretical risks 1, 3
• If vaccination must occur while on abatacept, proceed without delay—do not withhold vaccination waiting for an "optimal" window 2, 3

The live zoster vaccine (Zostavax) may be considered in less severely immunosuppressed patients, but only with extreme caution 1:

• Live vaccine should only be given to patients who are seropositive for varicella zoster antibodies to prevent primary varicella infection with the vaccine strain 1
• The safety profile in abatacept-treated patients is not well-established 1
• Given the availability of the safer recombinant alternative, live vaccine use in this population is generally not recommended 3

Critical Clinical Pitfalls

Breakthrough shingles can still occur despite vaccination because:

• The vaccine reduces but does not eliminate risk—even in immunocompetent individuals, vaccine efficacy is 90-97% for recombinant vaccine and 50-70% for live vaccine 4
• Patients on abatacept may have suboptimal vaccine responses due to T-cell modulation, though specific data are lacking 1
• The duration of vaccine protection may wane over time, particularly in immunosuppressed populations 3

Do not delay abatacept therapy to achieve vaccination if the rheumatic disease is active and requires urgent treatment 1. The risk of disease progression outweighs the theoretical benefit of improved vaccine response off medication.

Monitor for herpes zoster symptoms (unilateral dermatomal pain, vesicular rash) even in vaccinated patients, as the moderate baseline risk persists 1. Early antiviral treatment within 72 hours of rash onset significantly reduces complications 5.

Practical Algorithm

1. Pre-treatment assessment: Check varicella immunity status and vaccination history before starting abatacept 1
2. Vaccination timing: If patient is ≥50 years and not yet on abatacept, administer 2-dose Shingrix series (doses 2-6 months apart) 2
3. Already on abatacept: Administer Shingrix without delay; do not hold abatacept therapy 2, 3
4. Ongoing surveillance: Educate patients about shingles symptoms and maintain low threshold for early antiviral treatment 5
5. Post-exposure management: If breakthrough shingles occurs, treat promptly with antivirals regardless of vaccination status 5

The evidence consistently shows that while vaccination is beneficial and recommended, it does not eliminate the elevated herpes zoster risk conferred by abatacept's immunomodulatory effects 1.