Vaccination Against Pneumococcal in Naïve Abatacept Rheumatoid Arthritis Patients

Study Overview
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Brief Summary
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Is pneumococcal conjugate vaccine (which induces a T-dependent humoral response) more efficient than pneumococcal polysaccharide vaccine (which induces a T-independent humoral response) in RA patients treated with abatacept, biotherapy targeting T-cells? The investigator propose to conduct a prospective, multicenter (11 centers), randomized, open-label study. The patients are going to be randomized in 2 groups: patients of the first group will be vaccinated with the polysaccharide pneumococcal vaccine (Pneumo23®/Pneumovax®) whereas patients of the second group will be vaccinated with conjugate pneumococcal vaccine (Prevenar13®).

Detailed Description
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The study population will be all the RA patients between 18 and 85 years with instauration of a treatment by sub-cutaneous abatacept in association with methotrexate who agreed to participate to the study. At the time of their inclusion, patients will be randomized for receiving either pneumococcal polysaccharide vaccine (PPSV) or pneumococcal conjugate vaccine (PCV). The primary endpoint will be evaluated at one month after vaccination. The total of follow-up will be of 12 months. For the patients of the group PCV, the prime-boost strategy will be applied in order to be in accordance with the current French recommendation and a revaccination at 2 months after the initial vaccine will be realized with PPSV.

Official Title
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Comparison of Humoral Response to Conjugate Pneumococcal Vaccine and Polysaccharide Pneumococcal Vaccine in Rheumatoid Arthritis (RA) Patients Treated With Abatacept

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: pneumococcal polysaccharide vaccine
* Biological: pneumococcal conjugate vaccine
* Drug: Abatacept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: RA according to American College of Rheumatology (ACR)/European League Against rheumatism (EULAR) 2010 criteria Disease Activity Score (DAS) 28 ≥ 3.2 Initiation of a treatment by sub-cutaneous abatacept in combination with methotrexate (MTX), whatever treatment they were receiving before (apart from rituximab (RTX) in the last year) Patient has signed study consent form Exclusion Criteria: age < 18 or > 85 year dementia patients subjects to legal protection measures Corticosteroids ≥ 10mg/d the day of inclusion Patient who had a pneumococcal vaccination in the previous 3 years Last pneumococcal vaccination < 3 year rituximab in the last year History of anaphylactic response to a vaccination Contraindications to abatacept or methotrexate Pregnancy or pregnancy wish Breast feeding Patient who currently abuse drugs or alcohol Subject who have received any live vaccines within 3 months of the anticipated first dose of study medication. Subject who have receive any vaccine within 1 month of the anticipated first dose of the study medication and for all the duration of the study Patient with contraindication to intramuscular injections Subject with respiratory insufficiency Subject at risk for Tuberculosis. Blood transfusion within the 3 months previous to the study and for all the duration of the study. Concomitant biologic disease-modifying antirheumatic drug (DMARD) Within 4 weeks of receiving treatment with any investigational drug. Patient positive for hepatitis B surface antigen Patient who are positive for hepatitis C antibody if the presence of hepatitis C virus was also shown with polymerase chain reaction or recombinant immunoblot assay.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: pneumococcal polysaccharide vaccine<br>Patients are vaccinated vith Peumo23/Pneumovax on the first day. Abatacept started on frst day. | Biological: pneumococcal polysaccharide vaccine<br>* Vaccination with PPSV on first day. NB : PPSV vaccine Pneumo23 has been replaced in September 2017 by the equivalent vaccine Pneumovax because of the stop of commercialization of Pneumo23 in France by the pharmaceutical company.<br>* Other names: Pneumo23/Pneumovax;Drug: Abatacept<br>* Abatacept started on frst day<br>* Other names: Orencia;|
| Active Comparator: pneumococcal conjugate vaccine<br>Patients are vaccinated with Prevenar13 on the first day, and with Pneumo23/Pneumovax two months later. Abatacept started on frst day. | Biological: pneumococcal conjugate vaccine<br>* Patients are vaccinated with Prevenar13 on the first day, and with Pneumo23/Pneumovax two months later.<br>* Other names: Prevenar13;Drug: Abatacept<br>* Abatacept started on frst day<br>* Other names: Orencia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral response comparison after vaccination (number of patient with at least a two-fold increase of the antibody titer for at least 3 of the 5 serotypes of interest : 1,3 14, 7F, 19A) | To compare the rate of responders, at one month after vaccination, between patients vaccinated with PCV and patient vaccinated with PPSV. | 1 month after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Side Effect frequency (number of side effect at each patient's visit for both groups) | Comparison of the frequency of side effects between the 2 groups at 1, 2, 6 and 12 months | 1, 2,6 ans 12 months after inclusion | 
| Prime boost strategy efficacity evaluation (number of responder in the PCV group) | Calculation of the rate of responders, in the PCV group, at 4 month after re-vaccination by a dose of PPSV | 6 months after inclusion | 
| Long term immune response after vaccination | Comparison between the 2 groups of the rate of responders at 6 and 12 months after vaccination | 6 and 12 months after vaccination | 
| Comparison between the 2 groups of the opsonophagocytosis activity of the antibodies produced | Comparison between the 2 groups of the opsonophagocytic titers (OPA) at 1, 2, 6 and 12 months after vaccination | 1, 2, 6 and 12 months after vaccination | 
| Pneumococcal vaccination predictive factor identification | Analysis of the collected date to search for predictive factors of immune response after pneumococcal vaccination by comparison of the rates of responders within each group, according to age, gender, RA activity, MTX dosage, corticosteroid, dosage, therapeutical history | 12 month after last patient inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccination against Pneumococcal, Naïve Abatacept patients