Induction of Immunity Against Streptococcus Pneumoniae in Adults With Inflammatory Bowel Disease
Condition: Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative
MeSH terms: Crohn Disease; Intestinal Diseases; Inflammatory Bowel Diseases; Colitis, Ulcerative
Study type: Interventional
Phase: Phase 4

Summary: 
      Patients with inflammatory bowel disease are at increased risk for infections due to their
      baseline disease and the subsequent immunocompromising regimen. Streptococcus pneumoniae
      (pneumococcus) has a high mortality and morbidity, particularly in immunosuppressed patients.
      A polysaccharide vaccine covering 23 different serotypes of pneumococcus (PPSV23) is
      currently recommended to immunocompromised patients to reduce their risk of invasive
      pneumococcal infections (such as bacteremia, meningitis, or pneumonia). Its immunogenicity is
      however limited, both in magnitude and duration, even in healthy individuals. Several studies
      have investigated the immunogenicity of PPSV23 in patients with IBD and have reported a
      marked inhibitory effect of immunosuppressive therapy on vaccine responses.

      A pneumococcal conjugated vaccine (PCV) was originally developed to protect young children
      and demonstrated as highly effective and safe. PCV13 contains polysaccharides from thirteen
      different serotypes, conjugated to an inactivated diphtheria toxin, and has the capacity to
      induce both primary and memory responses. PCV also appears much more immunogenic than PPSV23
      in immunocompromised pediatric and adult patients. Whether some therapeutic regimens may
      nevertheless prevent the induction of protective responses by PCV13 is yet unknown.

      To date, no study has yet reported the immunogenicity / safety of PCV13 in adult IBD
      patients.

      Study's objectives

        -  Primary objective: evaluate the immunogenicity and safety profile of PCV13 immunization
           in IBD patients

        -  Secondary objective: evaluate the relative influence of treatment and disease on immune
           responses to PCV13 immunization

        -  Tertiary objective: evaluate the immunity/vulnerability against vaccine-preventable
           diseases (VZV, measles) in the IBD cohort of Switzerland (optional, depending on funds)
    

Detailed description: 
      A. Inclusion:

      Patients are eligible for this study if they are part of the SIBDCS and are followed in
      Switzerland in Geneva, Vaud, Neuchatel or Bern. Gastroenterologist will present the study to
      the patient during a routine follow-up visit. Inclusion will be cumulative, into 2 groups of
      150 patients without (Group 1) or with (Group 2) immunosuppressive treatments.

      B. Intervention

        1. Vaccine history evaluation: A questionnaire will be filled at baseline including
           questions to establish patients' history of vaccine-preventable diseases and/or
           immunizations.

        2. Serologic evaluation: Blood will be taken at inclusion for a baseline serological
           evaluation against pneumococcus. Antibody analyses will be performed using enzyme linked
           immunosorbent assays (ELISA) to quantify antigen-specific immunoglobulin G (IgG)
           antibodies. Serological evaluation against tetanus, measles and VZV could be performed
           through a study extension, depending on funds available.

        3. Pneumococcal immunization: PCV13 (1 dose=0.5ml, intra-muscular) will be administrated
           during the same inclusion visit.

           Optional intervention (depending on available funds):

        4. Additional missing immunizations could be identified by the study team on an
           individualized level, based on the patient's immunological record, and presence or
           absence of immunosuppression.

      C. Assessment of effectiveness:

      A second blood sampling will be scheduled 2 months (minimum 1, maximum 4) after PCV13
      administration and will to assess vaccine response to PCV13.

      D. Assessment of safety:

      Vaccine safety will be monitored using standardized diary cards recording local and systemic
      side effects at week 1, 2, 4, 6, 8 after immunization. Patient will also be contacted by
      phone at week 6 by the investigator who will ask standardized questions regarding vaccine
      safety. Potential changes in disease activity (vaccine-induced flares) will be monitored
      during the following 6 months, through data collected in the SIBDCS database.
    

Intervention name(s): 13-valent pneumococcal conjugated vaccine (PCV13)
Intervention type(s): Biological
Intervention description(s): Immunization with 1 dose of PCV13 (=0.5ml) intra-muscular
Other intervention name(s): Streptococcus pneumoniae conjugated vaccine; PCV13 (Prevenar13®, Pfizer AG, Zurich); Swissmedic authorization number 60129
Intervention MeSH terms: Vaccines
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention