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Vaccination Against Pneumococcal in Naïve Abatacept Rheumatoid Arthritis Patients

Not Applicable
Completed
Conditions
Rheumatoid Arthritis
Interventions
Biological: pneumococcal polysaccharide vaccine
Biological: pneumococcal conjugate vaccine
Registration Number
NCT02547493
Lead Sponsor
University Hospital, Montpellier
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
80
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
pneumococcal polysaccharide vaccinepneumococcal polysaccharide vaccinePatients are vaccinated vith Peumo23/Pneumovax on the first day. Abatacept started on frst day.
pneumococcal conjugate vaccinepneumococcal conjugate vaccinePatients are vaccinated with Prevenar13 on the first day, and with Pneumo23/Pneumovax two months later. Abatacept started on frst day.
pneumococcal conjugate vaccineAbataceptPatients are vaccinated with Prevenar13 on the first day, and with Pneumo23/Pneumovax two months later. Abatacept started on frst day.
pneumococcal polysaccharide vaccineAbataceptPatients are vaccinated vith Peumo23/Pneumovax on the first day. Abatacept started on frst day.
Primary Outcome Measures
NameTimeMethod
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)1 month after vaccination

To compare the rate of responders, at one month after vaccination, between patients vaccinated with PCV and patient vaccinated with PPSV.

Secondary Outcome Measures
NameTimeMethod
Side Effect frequency (number of side effect at each patient's visit for both groups)1, 2,6 ans 12 months after inclusion

Comparison of the frequency of side effects between the 2 groups at 1, 2, 6 and 12 months

Prime boost strategy efficacity evaluation (number of responder in the PCV group)6 months after inclusion

Calculation of the rate of responders, in the PCV group, at 4 month after re-vaccination by a dose of PPSV

Long term immune response after vaccination6 and 12 months after vaccination

Comparison between the 2 groups of the rate of responders at 6 and 12 months after vaccination

Comparison between the 2 groups of the opsonophagocytosis activity of the antibodies produced1, 2, 6 and 12 months after vaccination

Comparison between the 2 groups of the opsonophagocytic titers (OPA) at 1, 2, 6 and 12 months after vaccination

Pneumococcal vaccination predictive factor identification12 month after last patient inclusion

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

Trial Locations

Locations (11)

CHU Nord

🇫🇷

Amiens, France

CHRU de Montpellier

🇫🇷

Montpellier, Hérault, France

CHU Pellegrin

🇫🇷

Bordeaux, France

CHU Bicêtre

🇫🇷

Le Kremlin-bicêtre, France

CHRU Roger Salengro

🇫🇷

Lille, France

CHU Carémeau

🇫🇷

Nîmes, France

CHU Montpied

🇫🇷

Clermont-Ferrand, France

CHU La pitié salpétriere

🇫🇷

Paris, France

CHU Orléans

🇫🇷

Orléans, France

CHPG Monaco

🇲🇨

Monaco, Monaco

CHU Hautepierre

🇫🇷

Strasbourg, France

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