Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)—Part 2: Inactivated Vaccines

Abstract Background and Aims The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines. Methods Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. Results Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada’s National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27–45 years. Conclusions Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.


Centers for Disease Control (CDC) 3 (General Population) Canadian Immunization Guide (PHAC/NACI) 4 (General Population)
Haemophilus influenzae type b (Hib) "In pediatric patients with IBD, 5 years of age and younger, we recommend Hib vaccine be given." Strong recommendation, moderate-certainty of evidence --Routine Hib vaccination at age 2-6 months of age. Booster at age 12-15 months. Catch-up Hib vaccination until 59 months of age.
Primary series of Hib at age 2, 4, 6 months of age. Booster at age 12-23 months. Catchup Hib vaccination until 5 years of age. "In unimmunized pediatric patients with IBD, older than 5 years of age, we suggest Hib vaccine be given."

Conditional recommendation, low-certainty of evidence
In unimmunized adults and children age 60 months or older, Hib is recommended only for highrisk medical conditions for invasive Hib disease.
In unimmunized adults and children older than 5 years of age, Hib is recommended only for high-risk medical conditions for invasive Hib disease. "In unimmunized adult patients with IBD, we suggest Hib vaccine be given."

Conditional recommendation, very lowcertainty of evidence
Hib is not recommended routinely for unimmunized adults and children older than 5 years.
Hib is not recommended routinely for unimmunized adults and children older than 5 years. Routine HPV vaccination for girls and women age 9 to less than 27 years. Routine HPV vaccination for boys and men age 9 to less than 27 years. "In male patients with IBD age 9 to 26, we suggest HPV vaccine be given." Conditional recommendation, very lowcertainty of evidence Routine meningococcal conjugate vaccine to infants at 12 months.
Infants at higher risk of invasive meningococcal disease should receive meningococcal vaccines starting at 2 months of age.
Routine meningococcal conjugate vaccines to adolescents and young adults (12-24 years) even if previously vaccinated as infant or toddler. In addition, serogroup B meningococcal vaccine may be considered on an individual basis. "In adult patients with IBD with a risk-factor for invasive meningococcal disease, we recommend meningococcal vaccines be given."

Strong recommendation, moderate-certainty of evidence
Routine meningococcal vaccines for children and adults who are at increased risk for invasive meningococcal disease.
Routine meningococcal vaccines for children and adults who are at increased risk for invasive meningococcal disease.
"In adult patients with IBD without a riskfactor for invasive meningococcal disease, the consensus group could not make a recommendation for or against giving meningococcal vaccines." Moderate certainty of evidence Pneumococcal "In pediatric patients with IBD, we recommend age-appropriate pneumococcal vaccines be given." Strong recommendation, moderate-certainty of evidence "Pneumococcal vaccination should be given shortly before initiation of immunomodulators." "Adult patients with IBD receiving immunosuppressive therapy should receive pneumococcal vaccine Routine PCV13 for children younger than 2 years of age.
Routine PCV13 for infants 2 months to less than 12 months of age.
Older children who did not receive the complete schedule should be "In adult patients with IBD not on immunosuppressive therapy, with a risk-factor for pneumococcal disease, we recommend pneumococcal vaccines be given." Strong recommendation, moderate-certainty of evidence with both the PCV13 and PPSV13, in accordance with national guidelines." Conditional recommendation, very low level of evidence vaccinated (see CIG guide for catchup schedule).
"In adult patients with IBD on immunosuppressive therapy, we suggest pneumococcal vaccines be given."

Conditional recommendation, low-certainty of evidence
For children over the age of 2 and adults with certain high-risk medical conditions, both PCV13 and PPSV23 vaccines are recommended.
Children age 2 months to less than 18 years at high risk of invasive pneumococcal disease should receive both PCV13 and PPSV23 vaccines: PCV13 in infancy (3+1 schedule); PPSV23 at 24 months; PPSV23 in older children and adolescents.
For adults older than 18 years of age at high risk for invasive pneumococcal disease, both PCV13 and PPSV23 are recommended. "In adult patients with IBD not on immunosuppressive therapy and without a riskfactor for pneumococcal disease, the consensus group could not make a recommendation for or against giving pneumococcal vaccines" Moderate certainty of evidence Routine childhood vaccination for children age older than 12 months, adolescents, and adults age 50 years or younger without evidence of immunity.
Also recommended for adults older than 50 years known to be serologically susceptible to varicella based on laboratory testing.
When considering immunization of an immunocompromised person with a live vaccine, approval from the individual's attending physician should be obtained before vaccination. For complex cases, referral to a physician with expertise in immunization or immunodeficiency is advised. In cases in which, in the opinion of the physician, the benefits of immunization outweigh the risks, any of the univalent varicella vaccines can be used.
"In varicella-susceptible pediatric patients with IBD on immunosuppressive therapy, we suggest against giving varicella vaccine be given." Conditional recommendation, very lowcertainty of evidence "In varicella-susceptible adult patients with IBD not on immunosuppressive therapy, we suggest varicella vaccine be given." Conditional recommendation, very lowcertainty of evidence "In varicella-susceptible adult patients with IBD on immunosuppressive therapy, we suggest against giving varicella vaccine." Conditional recommendation, very lowcertainty of evidence