Immunogenicity of Influenza, Pneumococcal and Hepatitis B Vaccines in IBD Patients Treated With Vedolizumab
Condition: Inflammatory Bowel Diseases
MeSH terms: Hepatitis B; Intestinal Diseases; Inflammatory Bowel Diseases
Study type: Observational

Summary: 
      Patients with Crohn's disease (CD) and ulcerative colitis (UC) are often treated with
      medications that suppress the immune system. These patients are therefore at increased risk
      for developing infections, such as influenza, pneumonia, and hepatitis B, which may be
      prevented by vaccination. While awareness is increasing among gastroenterologists of the
      importance of vaccinations in the IBD patient, there continues to be some question of the
      effectiveness of vaccination in immunosuppressed patients. It has been previously shown that
      patients on immunosuppressive therapy with certain biologic medications (the TNF-blockers:
      infliximab and adalimumab) had an impaired immune response to vaccination as compared to
      healthy controls, as the mechanism of immunosuppression for these agents is systemic.
      Vedolizumab, a biologic medication for CD and UC approved in May 2014, targets the α4β7
      integrin, a key component of gut immunity, and as such it has been hypothesized that with
      this agent effects are gut specific. There is limited data that suggests that in healthy
      patients given vedolizumab do not have an altered response to parentally administered
      vaccines, however there are no studies in the CD and UC population describing this.
      Additionally, IBD patients treated with vedolizumab are frequently also on concomitant
      therapy with an immunomodulator (6-mercaptopurine, azathioprine, or methotrexate), and these
      patients ability to mount an immune response has not been demonstrated.
    

Detailed description: 
      The purpose of this study is to determine immune response rates to (a) influenza, (b)
      pneumococcal, and (c) hepatitis B vaccines in IBD patients receiving vedolizumab therapy
      compared to patients on other therapies for IBD.

      Four study groups will be established -- 1. Group A - IBD patients on vedolizumab
      monotherapy. 2. Group B - IBD patients receiving combination treatment with vedolizumab and
      concomitant immunomodulator therapt (methotrexate, azathioprine, or 6-mercaptopurine). 3.
      Group C - IBD patients on other biologic therapy (infliximab, adalimumab, certolizumab,
      golimumab, and ustekinumab). 4. Group D - IBD patients not taking any immunosuppressive
      therapy. Patients in all groups should have been on stable treatment for IBD for at least
      three months.

      For each of the four vaccines included in this study (influenza, PCV-13, PSV-23, hepatitis
      B), a total of 220 samples will be collected. Given that more than one of these vaccines may
      be clinically indicated for an individual patient, a single patient may receive more than one
      vaccine, and therefore can be included in the immune response analysis for each vaccine they
      receive.

      Once the subject has signed consent and enrolled in the study, the following procedures will
      take place:

      Baseline/enrollment visit: The subject will have a comprehensive medical history and physical
      exam performed at their baseline clinic visit. During this visit they will also fill out the
      10 question IBD quality of life questionnaire, a baseline serum sample will be obtained, and
      then receive the vaccine(s) indicated based on their vaccination history. These vaccines
      include, for pneumococcal pneumonia - PSV-23 and PCV-13 (both given as a single dose of 0.5
      mL intramuscularly in the deltoid region of the upper arm), for influenza - Afluria or
      Fluzone for patients over 65 year of ago (both given as a single dose of 0.5 mL
      intramuscularly in the deltoid region of the upper arm), and for hepatitis B - Energix
      (administered in a three dose series with 1.0 mL given at 0, 1, and 6 months, or for patients
      receiving a booster a single intramuscular dose of 1.0 mL will be given). Subjects will be
      instructed to call the study team for any concerns or any development of fever, chills, rash
      or other concerning symptom.

      Follow up phone call: Subjects will receive a follow-up phone call 2 weeks after vaccination
      to identify any adverse effects including fevers or chills, rash, and visits to the emergency
      room or to their primary care physicians.

      Follow up visit: At 3-4 weeks after vaccination, patients will have a visit where serum will
      again be obtained. Patients will also be asked about any adverse events such as fevers or
      vaccine reactions, as well as complete the 10 question IBD quality of life questionnaire
      (IBDQ).
    

Intervention name(s): Pneumococcal Pneumonia vaccine; Influenza vaccine; Hepatitis B vaccine
Intervention type(s): Biological; Biological; Biological
Intervention description(s): Vaccination for pneumococcal pneumonia will be carried out with either the PSV-23 (Pneumovax, Merck, Whitehouse Station, NJ) or the PCV-13 (Prevnar 13, Pfizer, Philadelphia, PA). Either vaccine is administered in a single dose of 0.5 mL intramuscularly.; Influenza vaccination will be carried out with the 2017-2018 trivalent component vaccine (Afluria, Seqirus USA Inc., King of Prussia, PA) or for patients over 65 years of age (Fluzone, Sanofi Pasteur, Swiftwater, PA). Both of these vaccines are administered in a single dose of 0.5 mL intramuscularly.; Hepatitis B vaccination with be carried out with a single antigen, recombinant hepatitis B vaccine (Energix B, GlaxoSmithKline, Research Triangle Park, NC). This vaccine is administered in a three dose series with 1.0 mL given intramuscularly at 0, 1, and 6 months. For patients receiving a booster, a single intramuscular dose of 1.0 mL will be given.
Other intervention name(s): PSV-23 (Pneumovax, Merck, Whitehouse Station, NJ); PCV-13 (Prevnar 13, Pfizer, Philadelphia, PA).; Afluria; Fluzone; Energix B
Intervention MeSH terms: Vaccines
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Adult patients aged 18-75 with IBD (diagnosed by standard clinical, radiographic,
        endoscopic, and histopathologic criteria) receiving care at Boston Medical Center, Center
        for Digestive Disorders.