Clinical trial NCT02547493: Vaccination Against Pneumococcal in Naïve Abatacept Rheumatoid Arthritis Patients
Official title: Comparison of Humoral Response to Conjugate Pneumococcal Vaccine and Polysaccharide Pneumococcal Vaccine in Rheumatoid Arthritis (RA) Patients Treated With Abatacept
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rheumatoid Arthritis
Keywords: Vaccination against Pneumococcal
Naïve Abatacept patients
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2015-09-11
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: 1 month after vaccination
Secondary outcomes:
measure: Side Effect frequency (number of side effect at each patient's visit for both groups)
timeFrame: 1, 2,6 ans 12 months after inclusion
measure: Prime boost strategy efficacity evaluation (number of responder in the PCV group)
timeFrame: 6 months after inclusion
measure: Long term immune response after vaccination
timeFrame: 6 and 12 months after vaccination
measure: Comparison between the 2 groups of the opsonophagocytosis activity of the antibodies produced
timeFrame: 1, 2, 6 and 12 months after vaccination
measure: Pneumococcal vaccination predictive factor identification
timeFrame: 12 month after last patient inclusion
Other outcomes:
Locations:
city: Montpellier
country: France
facility: CHRU de Montpellier
state: Hérault
city: Amiens
country: France
facility: CHU Nord
city: Bordeaux
country: France
facility: CHU Pellegrin
city: Clermont-Ferrand
country: France
facility: CHU Montpied
city: Le Kremlin-bicêtre
country: France
facility: CHU Bicêtre
city: Lille
country: France
facility: CHRU Roger Salengro
city: Nîmes
country: France
facility: CHU Carémeau
city: Orléans
country: France
facility: CHU Orléans
city: Paris
country: France
facility: CHU La pitié salpétriere
city: Strasbourg
country: France
facility: CHU Hautepierre
city: Monaco
country: Monaco
facility: CHPG Monaco
Study officials:
affiliation: CHRU de Montpellier
name: Jacques Morel, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: