Efficacy Safety Study of Flu Vaccine in Immunodepression Patients

Study Overview
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Brief Summary
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The primary purpose of the study is to compare the efficacy and safety of influenza vaccine in patients with inflammatory bowel disease (IBD) receiving immunosuppressive therapy with patients not receiving immunosuppressants . The main objective of the study is to evaluate the humoral immunogenicity of influenza vaccination in patients with IBD

Detailed Description
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Annual vaccination against influenza is recommended for those at high risk of complications, particularly among patients with immunodeficiency including those resulting from immunosuppressive treatments administered for a chronic inflammatory bowel disease (IBD). However, published data showing that influenza vaccination coverage is low in this population (<30%) due to lack of data on the effectiveness of vaccination in these patients and the theoretical risk of negative impact on the evolution of IBD. To improve influenza vaccination coverage of the population treated by immunosuppressants for a chronic IBD, it is essential to have data on the effectiveness of vaccination in these populations. The research aims to evaluate the immunogenicity of influenza vaccination in patients followed for a chronic IBD. Factors in choice of study population were as follows: IBD is a common disease. Among the inflammatory diseases treated with immunosuppressants and reaching patients under 65 years, IBD are among the most frequent. They result from an abnormal immune response to gut flora and their management often requires the prescription of immunosuppressive drugs (azathioprine, methotrexate, in particular) and more recently TNF-blockers; the existence of vaccine recommendations published recently for specific patients on immunosuppressive therapy at greatest risk of complications related to influenza; the fact that vaccinations have not been implicated in the pathogenesis of the disease; data showing that vaccination recommendations are poorly followed in this population. A recently published work found vaccination coverage against influenza of only 28% in a cohort of 169 patients treated for IBD; The methodology chosen is a phase III, prospective, open, vaccine trial. The primary endpoint is the humoral immunogenicity induced by the vaccine. The study is scheduled on 2 successive years to assess the value of annual vaccination repeated in this population treated with immunosuppressants. There is a benefit for patients to participate in this study because they are all vaccinated against influenza and will benefit from a clinical and laboratory monitoring in this study. Moreover, these patients are taken to be vaccinated in the event of a pandemic influenza

Official Title
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Prospective, Multicentre, Open-label Study Evaluating the Immunogenicity and Safety of Influenza Vaccine in Patients With Inflammatory Bowel Disease (IBD) Receiving or Not Immunosuppressive Therapy

Conditions
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Inflammatory Bowel Disease (IBD)

Intervention / Treatment
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* Drug: Vaccine
* Biological: Vaccine anti-H1N1


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : informed consent signed Age between 18 to 64 Patient suffering from chronic inflammatory bowel disease (Crohn's disease, ulcerative colitis, or indeterminate colitis) For patients receiving at least one immunosuppressive or anti-TNF therapy: treatment introduced for at least 3 months Patient willing to participate in the study throughout its duration and acceptance procedures related to the study (blood samples, self questionnaires, nasal swab and telephone follow-up) Exclusion criteria : Patient treated by corticosteroid alone without immunosuppressive or anti-TNF For women, being pregnant or positive pregnancy test Known allergy to any component of the study vaccine or a history of hypersensitivity reaction to influenza vaccination Fever (at least 37.5°C measured orally) or acute infection in the week prior to vaccination Received influenza vaccination in the 6 months preceding enrollment Known history of progressive neuropathy or Guillain-Barre Known infection with HIV and/or HBV (Ag-HBs positive) and/or HCV Other causes of severe immune deficiency Cellular therapy, immunoglobulin infusions, of blood products or monoclonal antibodies (except anti-TNF) in the 3 months prior to vaccination Patient deprived of freedom by an administrative or court order Patient non affiliated to a health social security system

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2<br>patients with IBD receiving immunosuppressants (TNF blockers excluded) (n=100) | Drug: Vaccine<br>* MUTAGRIP (2009-2010 winter) VAXIGRIP (2010-2011 winter)<br>|
| Experimental: 3<br>patients with IBD receiving immunosuppressants including TNF blockers (n=100) | Drug: Vaccine<br>* MUTAGRIP (2009-2010 winter) VAXIGRIP (2010-2011 winter)<br>|
| Experimental: 1<br>patients with IBD not receiving immunosuppressant (n=100) | Drug: Vaccine<br>* MUTAGRIP (2009-2010 winter) VAXIGRIP (2010-2011 winter)<br>|
| Active Comparator: 4<br>patients with IBD receiving immunosuppressants including TNF blockers (n=20) | Biological: Vaccine anti-H1N1<br>* patients who received the vaccine anti-H1N1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rate | Seroconversion rate in the overall population, defined as the geometric mean titers ratio post / pre-vaccination for each of the three vaccine strains | 3-4 weeks after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion factor | The seroconversion factor obtained for each of the three vaccine strains will be compared between each of the three groups (patients not receiving treatment, patients receiving immunosuppressants and patients receiving immunosuppressants including TNF) defined as the geometric mean titers ratio post / pre-vaccination for each of the three vaccine strains | 3 weeks and 6 months after vaccination | 
| Seroprotection rate against the three vaccine strains | The seroprotection rate (defined as the proportion of subjects attaining an anti-hemagglutinin titer ≥1:40) obtained 3-4 weeks after flu vaccination, against the three vaccine strains | 3 or 4 weeks after of vaccination | 
| Seroprotection rate in the general population | The seroprotection rate in the general population and according to the three groups of patients | 3 weeks and 6 months after vaccination | 
| Seroconversion rate, geometric mean titers ratio before and after vaccination by haemagglutination inhibition assay | The seroconversion rate, geometric mean titers ratio before and after vaccination by haemagglutination inhibition (HI) assay before and after vaccination | after 3 weeks of vaccination | 
| Comparison of seroprotection rates for each of the three vaccine strains obtained in each of three groups | Comparison of seroprotection rates for each of the three vaccine strains obtained in each of three groups (patients not receiving treatment, patients receiving immunosuppressants and patients, receiving immunosuppressants including TNF) | 3 weeks and 6 months of vaccination | 
| Comparison of seroconversion factors obtained after 1 or 2 vaccinations in each of three groups of inflammatory bowel disease (IBD) and in the entire population |  | After 3 weeks of vaccination | 
| Number of influenza episodes and confirmed flu during each influenza peak season |  | 6 months after vaccination | 
| Occurrence of medical visits, emergency room visits, hospital admissions and deaths throughout the course of the study |  | 18 months after vaccination | 
| Occurrence and intensity of local and general adverse events within 5 days after vaccine administration |  | 5 days after vaccination | 
| Search of the determining factors to the influenza vaccine response | Search of the determining factors to the influenza vaccine response: sex, age, previous vaccination against influenza, chronic smoking, the presence of other comorbidities (diabetes, renal failure, cirrhosis, ..), the nature of the IBD, the nature of the treatment of IBD and their duration, the number of immunosuppressive treatments associated and Disease Activity Index score of IBD at the vaccination time | 18 months after vaccination | 
| Sub-immunological study | Sub-immunological study each year of the study, the first and the second year (n=60, 20 patients per group): To determine if the LT-CD4 induction at J21-28 is correlated with the antibody anti-vaccines concentration measured within 6 months. To determine if the basal concentrations of anti-flu LT-CD4 at J21-J28 is correlated with the antibody anti-vaccines concentrations measured within 6 months. | 6 months after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inflammatory bowel disease (IBD), immunosuppressed or non-immunosuppressed, influenza vaccine, antibody titers, seroprotective titers, vaccine-associated adverse events