Patients with inflammatory bowel disease (IBD) are at an increased risk for infections as a consequence of their disease, and this risk may be further amplified by certain immunosuppressive regimens (1–3). Many of these infections may be preventable with routine immunization and with the COVID-19 pandemic preventing vaccine preventable disease (VPD) is more important than ever (4). We present our approach for optimal vaccine use in patients with IBD to reduce the burden of VPD.
IMPROVING VACCINE UPTAKE
Patients with IBD historically have lower rates of vaccination than the general population because of several barriers including uncertainty as to which provider is responsible for recommending and providing age-appropriate vaccines. Gastroenterology providers must assume or share the responsibility for recommending or providing appropriate vaccines to protect their patients. In addition, providers should recommend that patients' family members be up to date with their immunization schedule to provide a “cocoon” vaccination strategy. To improve immunization rates, providers should consider implementing simple interventions such as using a medical assistant to review the immunization history and administer influenza and pneumococcal vaccines under delegation protocols. This allows providers to focus on patients who are vaccine hesitant to review the benefits and dispel misconceptions about vaccines. Furthermore, certain vaccines (influenza, pneumococcal, and hepatitis B) are stocked in our offices and administered during office visits to increase vaccine uptake.
SPECIAL IMMUNIZATION CONSIDERATIONS FOR PATIENTS WITH IBD
We recommend following the adult immunization schedule from the Advisory Committee on Immunization Practices (ACIP) except for instances where vaccine use might be recommended because of an increased risk for VPD in patients with IBD (5) (Table 1). In addition, certain therapies used to treat IBD may lower the immunogenicity of vaccines and require optimization of the adult immunization schedule (4) (Table 2).
Patients with IBD are at an increased risk for influenza compared with the general population and are more likely to require hospitalization (2). Furthermore, those treated with antitumor necrosis factor (TNF) monotherapy or combination therapy (anti-TNF and immunomodulator) may have a lower response to the inactived influenza vaccine (IIV) (6). The standard dose IIV is recommended for all adults each season, but certain patients with IBD may benefit from a different vaccine preparation. The high dose IIV induces higher antibodies in healthy adults older than 65 years and patients with IBD on anti-TNF monotherapy when compared with standard dose. We recommend high dose IIV for adult patients with IBD older than 65 years and those treated with anti-TNF monotherapy (7,8).
Patients with IBD are also at a one and a half times higher risk for pneumonia compared with age-matched controls (9). A large population-based study showed that the increased risk of invasive pneumococcal disease starts years before and continues after the diagnosis of IBD. Immunosuppressive medications, such as anti-TNF therapy and steroids, did not increase the risk, suggesting that the risk may be related to an underlying altered immune function (1). Both pneumococcal conjugate and pneumococcal polysaccharide vaccines are recommended by the ACIP for patients planning to initiate or already on systemic immunosuppression (5). Similar to influenza vaccine, patients on anti-TNF monotherapy or combination therapy may have a blunted vaccine response to pneumococcal vaccines (10). Thus, we recommend both pneumococcal vaccines be administered at diagnosis and before starting immunosuppression to allow for a normal vaccine response (Figure 1).
Patients with IBD have a 2-fold increased risk of herpes zoster (HZ) irrespective of whether they are on immunosuppressive therapy compared with the general population (11). In addition, 40-year-old patients with IBD are at a greater risk of HZ than healthy 50-year-olds for whom the ACIP currently recommends HZ immunization (5). Treatment with immunosuppressive therapies such as thiopurines, corticosteroids, or anti-TNF therapy is independently associated with an increased risk to HZ (11). A recent study also found that flares in IBD and repeated corticosteroid exposure also increased the risk of HZ (3). Furthermore, tofacitinib, a new Janus Kinase inhibitor, is associated with a higher risk of HZ compared with conventional agents (12).
The ACIP states that the recombinant zoster vaccine (RZV) series is the preferred vaccine for all immunocompetent adults aged 50 years and above (5). They do not provide formal recommendations for immunosuppressed populations, but RZV is safe and immunogenic in other immunosuppressed populations (13). All patients with IBD aged 50 years and older should receive the RZV series, but certain patients with IBD younger than 50 years may benefit from the RZV series. Those at an increased risk are patients aged 40–49 years with a history of HZ, those requiring repeated courses of corticosteroids, those on combination therapy requiring corticosteroids, and patients on tofacitinib with one of the following risk factors: oral corticosteroid use at baseline, Asian race, history of diabetes mellitus, history of previous anti-TNF failure, or chronic use of 10 mg twice a day (3,12). Insurance coverage should be verified before vaccine administration because these recommendations do not follow the 2020 adult ACIP immunization schedule (5).
DETERMINING IMMUNITY TO VPD IN PATIENTS WITH IBD
Most inactivated and live vaccines do not have a commercially available serologic test that is a correlate of vaccine-induced immunity. Hepatitis B vaccine is a notable exception. The ACIP recommends that patients with documentation of age-appropriate vaccines should be considered immune rather than relying on serologic tests to determine vaccine-induced immunity (14,15). Measles outbreaks have raised concerns among providers and patients regarding whether immunosuppressed patients with IBD are immune. Live pediatric vaccines induce an immune response that is virtually identical to that produced by natural infection and induce immunity in almost all recipients (16). The vaccine-induced antibody concentrations are often lower than those compared with primary infection, but these lower antibody concentrations are not indicative of lower sustained protection (14,15). In addition, the vaccine-induced antibody concentrations may not be measured adequately with commercially available serologic tests. Researchers from the Centers for Disease Control and Prevention (CDC) found that commercial enzyme-linked immunosorbent assay had a 34% false-negative rate when compared with their more sensitive assay (17). Furthermore, systemic immunosuppression does not seem to affect sustained antibody concentrations to measles, mumps, and rubella in adults with IBD who completed the series on average 17 years earlier compared with healthy controls (18). Therefore, we recommend following the ACIP recommendation that appropriate immunization history is acceptable evidence for immunity for measles, mumps, and rubella and varicella. They recommend against serologic screening for measles, rubella, or varicella in persons with presumptive immunity by these criteria (Figure 2) owing to a potential false-negative serologic test (14,15). A complete immunization history should be obtained on initial diagnosis of IBD, and it should be included in any transition of care whether from pediatric to adult or between adult providers. Obtaining a patient immunization history is easier than in the past because most states have statewide web-based immunization registries, although most are not linked to the EMR.
ADMINISTRATION OF LIVE TRAVEL VACCINES
A live travel vaccine may be recommended for an immunosuppressed patient with IBD. We recommend providers be familiar with vaccinating the traveling patient with IBD because it is a relatively common clinical scenario (Table 3). Travel clinic consultations are essential to determine which infections may be endemic to the region that the patient will be visiting but these clinicians may not be familiar with the risk of holding immunosuppressive therapy to administer a live vaccine. Thus, providers should counsel patients on the risk of holding immunosuppressive therapy because potential loss of response to biologic therapy or disease relapse and whether travel is advised. Emerging evidence suggests that live vaccines may be safe in some immunosuppressed patients depending on the type of immunosuppressive regimen and live vaccine (19). However, experts from the CDC do not recommend live vaccine administration in a patient on severely immunosuppressive therapy until prospective studies are available evaluating safety (Figure 3). If a live travel vaccine, such as yellow fever, is required, experts from the CDC recommend providers wait 3 months after discontinuation of severely immunosuppressive therapies before administration (20).
In conclusion, providers caring for patients with IBD have an opportunity to reduce the burden of VPD by assuming or sharing responsibility for appropriate vaccine administration. Furthermore, optimizing the adult immunization schedule may reduce the burden of VPD in patients with IBD.
CONFLICTS OF INTEREST
Guarantors of the article: Freddy Caldera, DO, MS, Mary S. Hayney, PharmD, MPH, Francis A. Farraye, MD, MSc.
Specific author contributions: Conceived the idea for the paper, did the initial literary search, and wrote the manuscript: F.C. M.S.H.: edited the manuscript and reviewed recommendations; edited the manuscript and reviewed recommendations.
Financial support: None to report.
Potential competing interests: None to report. F.C. has received research support from Takeda Pharmaceuticals and Sanofi. He has been a consultant for Takeda, GSK and Celgene. F.C. has served on advisory boards for Glaxo, Smith Kline, Janssen, Merck, Pfizer and Takeda.
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