INTRODUCTION
Patients with inflammatory bowel disease (IBD) are often treated with long-term immunosuppressive (IS) therapies such as anti-tumor necrosis factor (TNF) drugs and newer drugs such as anti-integrin, anti-interleukin, or Janus kinase inhibitor drugs. Such patients can be at increased risk of infections [
1,
2]. Several infections including influenza infection, pneumococcal infections, herpes zoster (HZ) infection, or hepatitis B infection in IBD patients treated with IS therapy are potentially preventable through vaccination. Therefore, adequate immunization for vaccine-preventable infectious diseases is currently recommended for all patients with IBD [
3]. The vaccination status of the patient should be determined at the time of diagnosis, and recommended vaccinations should be administered [
3]. Thus, the American College of Gastroenterology and European Crohn’s and Colitis Organisation developed guidelines for primary care physicians and gastroenterologists to vaccinate IBD patients [
4,
5]. However, vaccination rates are lower among IBD patients than in the general population [
6,
7]. In a Western study on 958 patients, only 47.7% of IBD patients received the hepatitis B vaccine, 42.6% received the pneumococcal vaccine, and 34.1% received the hepatitis A vaccine [
6]. According to a Canadian survey, vaccination uptake rates were 61.3% for influenza, 10.3% for pneumococcus, 61.0% for hepatitis B, 52.0% for hepatitis A, 26.0% for varicella, 20.7% for meningococcus, 5.3% for HZ, and 11.0% for herpes papilloma virus (females only) [
8]. In another Belgian study, only 32% of patients were completely vaccinated according to the guidelines [
9]. The immunization program in India is still in the development phase, and the immunization rates of elective vaccines are low [
10]. Physicians in various Asian countries/regions may have different approaches and management strategies for vaccination among IBD patients. We aimed to assess current therapeutic approaches and clinical management strategies for vaccination in Asian patients with IBD in the clinical setting using a questionnaire-based survey.
DISCUSSION
IBD patients are at higher risk of infection due to treatment with long-term IS therapies [
7]. A large study on 140,480 IBD patients reported a higher risk of influenza (incidence rate ratio, 1.54; 95% confidence interval [CI], 1.49-1.63) [
11]. A meta-analysis of 14,590 IBD patients showed an elevated risk of any infection (odds ratio, 1.19; 95% CI, 1.10-1.29) and of opportunistic infections (odds ratio, 1.90; 95% CI, 1.21-3.01) [
12]. Several infections are potentially preventable though vaccination. Despite clinical guideline recommendations for vaccination in IBD patients, there is insufficient awareness about vaccinations [
13,
14]. The reasons for the low rates of vaccinations in IBD patients may be the doctor’s lack of awareness, uncertainties about vaccination outcomes, and concerns about potential side effects [
8,
15-
17]. A survey among American gastroenterologists revealed poor knowledge about recommended vaccinations for IBD patients [
14]. In one Korean study, gastroenterologists have insufficient knowledge about vaccination of IBD patients [
16]. In our survey including Asian physicians, vaccination suggestion rates were higher than those in other Western studies. In this survey, knowledge of vaccination was sufficient, good, and excellent in 74.2% of respondents. Many respondents (44.3%) were usually or always collecting information on vaccination, and about half of the Asian doctors (52.6%) were usually or always performing vaccination. The practicing gastroenterologist should be able to educate patients and counsel them about vaccines considering their safety and effectiveness; they should also inform patients about contraindicated vaccinations in immunosuppressed individuals.
Gastroenterologists treating IBD patients should understand the appropriate use of vaccines. All IBD patients should receive non-live vaccines including influenza vaccine, pneumococcal vaccine, and hepatitis A, hepatitis B, HPV, tetanus, and pertussis vaccines. However, live-attenuated vaccines such as measles, mumps and rubella, varicella, and HZ should be avoided in immunosuppressed patients on high doses of IMs and biologics. IMs should be withheld for a minimum of 2 weeks, preferably for 4 to 6 weeks after live vaccine administration [
4,
5,
18]. Live vaccines should be avoided for at least 3 months after discontinuing treatment with IMs and biologics therapies [
19]. Live vaccines could be safely administered in patients undergoing low dose immunosuppression therapy such as those receiving ≤ 20 mg of prednisone for ≤ 14 days, those receiving ≤ 0.4 mg/kg of methotrexate per week, those receiving ≤ 3 mg/kg of azathioprine per day, and those receiving ≤ 1.5 mg/kg of 6-mercaptopurine per day [
5]. Patients on monotherapy with thiopurines or biologics may have an adequate response to vaccination, but in patients on combination therapy, there could be reduced response to the vaccine [
20-
22]. However, there is a report of nearly a 40% and 70% lower chance of achieving an adequate response to vaccinations in patients on IM monotherapy and anti-TNF monotherapy, respectively, than in patients not on IM therapy [
20].
There are various international and country-specific guidelines tailored to each country regarding vaccination for IBD patients [
1,
3,
23]. It is important to understand immunization guidelines for IBD patients and convey recommendations to patients. However, in our study, 16.9% (65/384) of respondents never or rarely made such recommendations. According to the guidelines for IBD patients, the recommended rate of vaccinations was significantly different from a country perspective. Respondents in the “usually, always” group were more numerous in Korea than in China, Japan, and other countries. Although influenza vaccination, pneumococcal vaccination, hepatitis B vaccination rates were high, HAV and tetanus/diphtheria (Td) vaccination rates were low. Annual vaccination against influenza was recommended by most respondents (66.4%). IBD patients should receive pneumococcal vaccination with both PCV-13 and PPSV-23 vaccines. Interestingly, 68.2% of the respondents from Korea recommended the 5-year pneumococcal vaccine to every IBD patient, compared to only 13.1% and 12.9% of the respondents from China and Japan, respectively. Vaccination against HPV is recommended to all women aged under 26 years. After checking the immune status, vaccination against HAV and hepatitis B virus should be considered. The survey results of HAV vaccination indicated different approaches among Asian countries/regions. For example, in Japan, the majority of respondents (72.0%) never checked the hepatitis A serology test results and most (51.3%) never recommended vaccination against HAV. The reasons for this relate to the different insurance and domestic vaccination guidelines in each country/region. Our findings suggest that more attention needs to be given to HAV vaccination counselling.
Regarding the tetanus, diphtheria, and pertussis vaccine, a one-time tetanus, diphtheria, and pertussis vaccine and a Td booster every 10 years are recommended. Our findings indicated low rates of vaccination against diphtheria, tetanus, and pertussis (never, 35.2%; rarely, 29.4%). HZ vaccination is recommended in patients aged 50 years and above [
5]. IBD patients have an increased risk of HZ than non-IBD patients (incidence rate ratio, 1.68; 95% CI, 1.60-1.76) [
24]. Anti-TNF medication, corticosteroids, thiopurines and JAK inhibitors are associated with HZ infection [
25,
26]. Vaccination against varicella zoster is recommended in those without a clear history of chickenpox or those with no vaccination history [
5]. Two vaccines, i.e., live vaccine (ZVL, Zostavax®) and recombinant zoster vaccine (RZV, Shingrix®) are approved [
27]. If available, the inactivated vaccine (Shingrix®) should be used. Vaccination against meningococcus and yellow fever should be considered in special situations. Yellow fever is spread by mosquitoes and causes symptoms including fever, chills, headache, backache, and muscle aches. About 15% of people with yellow fever disease develop serious illness that can sometimes be fatal [
4]. Individuals traveling to certain parts of South America and Africa are at a risk of yellow fever. There are no data on yellow fever vaccination in patients with IBD under IS therapy. Patients with IBD who are immunosuppressed while traveling to areas where yellow fever is prevalent should consult with a travel medicine or infectious disease specialist prior to travel [
5].
This study had several limitations. The first limitation of this study is the response bias, i.e., even if the respondents did not fully understand or were not interested in a question, they had to respond; thus, their answers could be inaccurate. However, owing to the anonymous nature of the survey, respondents might have provided honest answers to the questions. The second limitation is that there was no question in the survey regarding severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination due to the lack of knowledge about SARS-CoV-2 vaccination at the time of the survey. SARS-CoV-2 vaccination is currently strongly recommended for IBD patients [
28]. Nevertheless, our study is the first to present data about vaccination in IBD patients in Asian countries/regions. The response rate to the questionnaire was acceptable and large number of respondents were geographically balanced among the Asian countries/regions.
Asian physicians appear to have enough knowledge on vaccines and performing vaccinations in patients with IBD. Influenza, pneumococcal vaccination, and hepatitis B vaccination rates were high. However, vaccination rates according to guidelines, target of pneumococcal vaccine, hepatitis A and Td vaccine rates were different among countries/regions. It is important to understand immunization guidelines for IBD patients and accordingly convey recommendations, notwithstanding differences between countries/regions regarding health insurance and national vaccination guidelines.
In conclusion, the present survey revealed that current approaches and clinical management of vaccination in IBD patients are mostly similar in Asian countries/regions; however, there are some differences among vaccines in some countries/regions. Although Asian physicians largely recommend vaccination, more awareness among doctors and Asian consensus regarding differences in IBD vaccination among countries/regions may be required.