Pneumococcal Vaccination of Crohn Patients

NCT ID: NCT01947010

Last Updated: 2015-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2014-08-31

Brief Summary

Inflammatory bowel disease (IBD) are at increased risk of infections. This increased susceptibility to infections is due to the disease itself, but also be-cause many patients with autoimmune conditions are treated with immuno-suppressive drugs, such as azathioprine and or TNF-a inhibitors.

Streptococcus pneumoniae (pneumococcus) is a cause of worldwide morbidity and mortality and one of the most common cause of bacterial meningitis in adults. Infection with pneumococcus can be prevented with vaccination. Two pneumococcal vaccine are used in Denmark, the 23 valent polysaccharide-based vaccine (23PPV) and the 13 valent of conjugate pneumococcal vaccines (PCV13).

In this study the investigators wish to study the effect of pneumococcal vaccination with either PPV23 or PCV13 in IBD patients treated with either TNF-a inhibitors, azathioprine or untreated.

Detailed Description

Patients with autoimmune diseases like inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) are at increased risk of infections. This increased susceptibility to infections is due to the disease itself, but also be-cause many patients with autoimmune conditions are treated with immuno-suppressive drugs. Different drugs are well-known suppressors of the immune system: Prednisolone, Azathioprine, Methotrexate (MTX), TNF-a inhibitors, and the newer biological agents such as, e.g., Rituximab (RTX), which is a drug used in the treatment of RA patients often in combination with MTX. The extent of immunosuppression induced by these therapeutic agents seems to depend, to some extent, on pharmacological dose/response relationships and on the combination of drugs, but individual variability plays a major role as well.

Prophylactic measures such as vaccination, quick upstart of antibiotics in case of fever and general information to patients about how to handle fever etc. are important in order to prevent as many cases of serious infections as possible among patients in immunosuppressive treatment.

Streptococcus pneumoniae is a cause of worldwide morbidity and mortality. Pneumococcal vaccines have been available since the early 1980's. The vaccine which has been licensed for immunization of children >2 years and adults is a polysaccharide-based vaccine (23PPV) consisting of capsule parts of the 23 most frequent serotypes of pneumococci. This vaccine elicits in normal immunocompetent persons a high antibody response, which lasts for approximately 10 years. Because the 23PPV is a polysaccharide-based vaccine, it induces a T-cell independent response with no memory and there-fore with no possibility of boosting. In 2001, the first generation of conjugate pneumococcal vaccines (PCV7) was licensed. In the PCV's, the capsule material from the pneumococci has been conjugated to a protein, which means that the vaccines can elicit a T-cell dependent immune response even in infants giving memory response and booster possibility. This vaccine has been licensed for use in children from 0-5 years, but studies suggest that PCV immunization might be useful in other groups of people as well etc. immunodeficient children and adults (especially now where the second-generation vaccines PCV10, PCV13 have been licensed covering more pneumococcal serotypes).

Some studies have shown that patients treated with immunosuppressive drugs cannot mount a sufficient antibody response upon vaccination whereas other studies suggest that these patient groups do respond to conventional vaccination.

It is recommended in the Danish guidelines for pneumococcal vaccination, that elderly patients with chronic diseases and patients with a decreased immune system are vaccinated against pneumococcal diseases. Accordingly, patients with Crohn's disease treated with TNF-a inhibitors are recommended pneumococcal vaccination.

In this study, the investigators aim to carry out an investigation of the response to pneumococcal vaccination in persons with Crohn's disease treated with TNF-a inhibitors and/or azathioprine, in order to determine if there is a place for the usage of conjugate vaccination in these patient groups.

Conditions

Crohns Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Crohn's patients treated with Azathioprine

Vaccination with PPV23 or Vaccination with PCV 13

Group Type: ACTIVE_COMPARATOR

Prevenar 13

Intervention Type: BIOLOGICAL

Pneumovax

Intervention Type: BIOLOGICAL

Crohn's patients treated with Azathioprine and TNFa inhibitors

Vaccination with PPV23 or Vaccination with PCV 13

Group Type: ACTIVE_COMPARATOR

Prevenar 13

Intervention Type: BIOLOGICAL

Pneumovax

Intervention Type: BIOLOGICAL

Crohn's disease patients without treatment

Vaccination with PPV23 or Vaccination with PCV 13

Group Type: ACTIVE_COMPARATOR

Prevenar 13

Intervention Type: BIOLOGICAL

Pneumovax

Intervention Type: BIOLOGICAL

Interventions

Prevenar 13

Intervention Type: BIOLOGICAL

Pneumovax

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Crohn's disease, receive immunosuppressive treatment or no treatment

Exclusion Criteria

• <18 years of age,
• pregnant,
• anemia,
• previously pneumococcus vaccination

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hvidovre University Hospital

OTHER

Sponsor Role: collaborator

Herlev Hospital

OTHER

Sponsor Role: collaborator

Statens Serum Institut

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andreas M Petersen, MD

Role: PRINCIPAL_INVESTIGATOR

Hvidovre University Hospital

Ole Ø Thomsen, MD

Role: PRINCIPAL_INVESTIGATOR

Herlev Hospital

Locations

Statens Serum Institut

Copenhagen, , Denmark

Countries

Denmark

References

Kantso B, Halkjaer SI, Ostergaard Thomsen O, Belard E, Gottschalck IB, Jorgensen CS, Krogfelt KA, Slotved HC, Ingels H, Petersen AM. Persistence of antibodies to pneumococcal conjugate vaccine compared to polysaccharide vaccine in patients with Crohn's disease - one year follow up. Infect Dis (Lond). 2019 Sep;51(9):651-658. doi: 10.1080/23744235.2019.1638519. Epub 2019 Jul 10.

Reference Type: DERIVED

PMID: 31290715 (View on PubMed)

Kantso B, Halkjaer SI, Thomsen OO, Belard E, Gottschalck IB, Jorgensen CS, Krogfelt KA, Slotved HC, Ingels H, Petersen AM. Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease. Vaccine. 2015 Oct 5;33(41):5464-5469. doi: 10.1016/j.vaccine.2015.08.011. Epub 2015 Aug 12.

Reference Type: DERIVED

PMID: 26275480 (View on PubMed)

Other Identifiers

BJK001

Identifier Type: -

Identifier Source: org_study_id