VACcination In Methotrexate Treated Rheumatoid Arthritis Patients (VACIMRA)

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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: Prevenar 13; Biological: Pneumo23 / Pneumovax; Drug: Methotrexate - Immediate; Drug: Methotrexate - Delay

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 276
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • CHU Nord
  • Bordeaux, France, 33000
    • CHU Pellegrin
  • Brest, France, 29609
    • CHU La Cavale Blanche
  • Clermont-Ferrand, France, 63003
    • CHU Montpied
  • Le Kremlin Bicetre, France, 94275
    • CHU Bicêtre
  • Le Mans, France, 72000
    • CH du Mans
  • Limoges, France, 87042
    • Chu Dupuytren
  • Marseille, France, 13005
    • CHU la Conception
  • Montpellier, France, 34295
    • CHU de Montpellier - Hôpital Lapeyronie
  • Nice, France, 06202
    • CHU de Nice - Hôpital l'Archet 1
  • Nîmes, France, 30029
    • CHU Caremeau
  • Orléans, France, 45000
    • CHU Orléans - Hôpital La Source
  • Paris, France, 75012
    • CHU Saint Antoine
  • Paris, France, 75013
    • CHU La Pitié Salpêtrière
  • Rennes, France, 35056
    • CHU de Rennes
  • Rouen, France, 76031
    • CHU Bois Guillaume
  • Saint Etienne, France, 42055
    • CHU Saint Etienne - Hôpital Nord
  • Strasbourg, France, 67098
    • CHU HautePierre
  • Toulouse, France, 31059
    • CHU Purpan
  • Tours, France, 37044
    • CHU Trousseau
• Monaco
  • Monaco, Monaco, 98000
    • CHPG Monaco - Hôpital Prince Grace de Monaco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Immediate group; 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; Vaccination at the beginning of the study (day 0); Other Names: Antipneumococcal vaccination; Biological: Pneumo23 / Pneumovax; 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; Other Names: Antipneumococcal vaccination; Drug: Methotrexate - Immediate; concerning immediate group, methotrexate is Initiated in the same time that the antipneumococcal vaccination by prevenar 13; Other Names: conventional methotrexate treatment
Experimental: period group; 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; Vaccination at the beginning of the study (day 0); Other Names: Antipneumococcal vaccination; Biological: Pneumo23 / Pneumovax; 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; Other Names: Antipneumococcal vaccination; Drug: Methotrexate - Delay; For "period group", methotrexate is Initiated & month after the antipneumococcal vaccination by prevenar 13; Other Names: Experimental methotrexate treatment

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Pfizer; Hôpital Cochin
• Investigators: Principal Investigator: Jacques MOREL, PU-PH, University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2013
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): July 10, 2019

Study Registration Dates

• First Submitted: September 10, 2013
• First Submitted That Met QC Criteria: September 10, 2013
• First Posted (Estimate): September 13, 2013

Study Record Updates

• Last Update Posted (Actual): August 3, 2020
• Last Update Submitted That Met QC Criteria: July 30, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Antipneumococcal vaccination; Methotrexate treatment
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Heptavalent Pneumococcal Conjugate Vaccine; Methotrexate
• Other Study ID Numbers: 9144 (OTHER: CTEP)