VACcination In Methotrexate Treated Rheumatoid Arthritis Patients

Study Overview
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Brief Summary
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To estimate the rate of immunological answer 1 month after antipneumococcal vaccination by the conjugated vaccine Prevenar13 ® in patients suffered from rheumatoid polyarthritis and who begin a treatement by methotrexate either in the same time, either 1 month later.

Detailed Description
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Patients suffering from rheumatoid polyarthritis have an increased risk to develop an infection compared to general population, with a more important mortality risk because pneumococcus is considered as one of the major pathogenic agents. Antipneumcoccal vaccination is recommended to patients suffering from chronic inflammatory rheumatism treated with immunosuppressants. Methotrexate is a long term treatment used in first intention for rheumatoid polyarthritis. A recent study shows a decrease of efficacity of antipneumoccal vaccination for patients suffering from rheumatoid polyarthritis treated by methotrexate. The tested hypothesis will be the presence of better vaccinal protection for patients suffered from rheumatoid polyarthritis after 1 month between antipneumococcal vaccination and the initiation of methotrexate. The objective is to compare immunologic response for antipneumococcal vaccination between patients who are vaccinated in the same time of initiation of methotrexate and patients who are vaccinated 1 month before the beginning of the treatment.

Official Title
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Lead Time of the Methotrexate Establishment and Vaccinal Protection Against the Pneumococcal Agent in Patients Affected With Rheumatoid Polyarthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: Prevenar 13
* Biological: Pneumo23 / Pneumovax
* Drug: Methotrexate - Immediate
* Drug: Methotrexate - Delay


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (>18 yeas old) suffers from rheumatoid arthritis considering ACR/EULAR 2010 criteria Rheumatoid arthritis considering 3,2<DAS<5,1 Patient did not treat by long term treatment or has stopped a treatment by sulfasalazine, hydroxychloroquine or methotrexate for at least 3 months Patient has never treated by biotherapy Patient has never vaccinated against pneumococcal Patient has signed study consent form Exclusion Criteria: Patient has ever treated by leflunomide or has treated previously by leflunomide (last 3 months) Patient is currently treated by methotrexate or has treated previously by methotrexate (last 3 months) Contraindication to methotrexate: renal insuffisance, alcoolic, chronic hepatisis, infectious condition, AIDS, hematological failure (cytopeny), pregnancy, obesity, diabet, respiratory disease, gastric ulcer Contraindication to corticotherapy Pregnancy or pregancy wish Nursing Absence of oral contraception for women of childbearing age Patient of age protected by law et deprived of liberty Subject who refuses to be vaccinated against pneumococcis agent Previous history of vaccination allergy (anaphylactic shok, Quincke oedema...) Gluten hypersensivity or intolerance Other vaccination during the last month before inclusion Ig perfusion during the last 3 months period before the study inclusion or during the study duration Patient currently treated by anticoagulant or has not been stopped for at least 48h before the study inclusion or hemostasis failure which is contraindicated with muscular injection Participation with an other clinical trial

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Immediate group<br>For these patients, the methotrexate treatment is initiated in the same time that the antipneumococcal vaccination by Prevenar13. A revaccination by Pneumo23/Pneumovax is administred 2 months after the first vaccination. Interventions : biological/vaccine and drug | Biological: Prevenar 13<br>* Vaccination at the beginning of the study (day 0)<br>* Other names: Antipneumococcal vaccination;Biological: Pneumo23 / Pneumovax<br>* Vaccination 2 months later the beginning of the study NB : Vaccine Pneumo23 has been replaced by equivalent vaccine Pneumovax in September 2017 because of the stop of commercialization of Pneumo23 in France by the pharmaceutical company<br>* Other names: Antipneumococcal vaccination;Drug: Methotrexate - Immediate<br>* concerning immediate group, methotrexate is Initiated in the same time that the antipneumococcal vaccination by prevenar 13<br>* Other names: conventional methotrexate treatment;|
| Experimental: period group<br>Methotrexate treatment is initiated 1 month later the first antipneumococcal vaccination by Prevenar13. A revaccination by Pneumo23/Pneumovax is administred 2 months after the first vaccination Interventions : biological/vaccine and drug | Biological: Prevenar 13<br>* Vaccination at the beginning of the study (day 0)<br>* Other names: Antipneumococcal vaccination;Biological: Pneumo23 / Pneumovax<br>* Vaccination 2 months later the beginning of the study NB : Vaccine Pneumo23 has been replaced by equivalent vaccine Pneumovax in September 2017 because of the stop of commercialization of Pneumo23 in France by the pharmaceutical company<br>* Other names: Antipneumococcal vaccination;Drug: Methotrexate - Delay<br>* For period group, methotrexate is Initiated & month after the antipneumococcal vaccination by prevenar 13<br>* Other names: Experimental methotrexate treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of immunological positive answer 1 month after antipneumococcal vaccination by the conjugated vaccine Prevenar13 ® in patients suffering from rheumatoid polyarthritis. | Patient who begins a treatement by methotrexate either in the same time, either 1 month later. An answer will be considered as positive if the patient answers in at least 3 on 5 of interest serotypes. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients in each group who will know fully immunological answer to 5 interest serotypes after the first antipneumococcal vaccination (Prevenar13) |  | 1 month | 
| Number of patients in each group who will know an immunological answer to 13 serotypes after the first antipneumococcal vaccination (Prevenar13) |  | 1 month | 
| Number of patients who will know a fully immunological answer (13 serotypes of vaccine) after a antipneumococcal revaccination with Pneumo 23. |  | 3, 6 and 12 months | 
| Number of patients who will suffer from adverse events in relation with the antipneumococcal vaccination |  | up to 12 months | 
| Frequency of occurence of disease spurts from the first vaccination until the end of the study |  | Up to 12 months | 
| occurence of the pneumococcal disease from the first vaccination to the end of the study. |  | 1, 6, 7 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antipneumococcal vaccination, Methotrexate treatment