Short summary

This is a randomized controlled, un-blinded phase 3 trial. The aim is to investigate the serological response after pneumococcal vaccination in rheumatoid arthritis patients, receiving either DMARDs (Disease Modifying Antirheumatic Drugs) or biological therapy. All patients will receive the 13-valent conjugated pneumococcal vaccine, Prevenar 13®, and the 23-valent polysaccharide pneumococcal vaccine, Pneumovax®. Follow up will be two years.

Rationale

During the last few years, patients undergoing biological treatment for rheumatoid arthritis have improved the prognosis significantly. At the same time, it has shown that the treatment is associated with a greater risk for infections, including severe bacterial infections, tuberculosis and other opportunistic infections with microorganisms, which normally would not lead to disease in healthy individuals. Data from several studies show that the risk is significantly increased initially, but decreases after the first year. Then the risk will be the same seen during DMARD therapy (Disease Modifying Antirheumatic Drugs).
However, it is a dynamic area where new drugs with other specific immune-modulating effects are being used (including IL -6 receptor antagonist Tocilizumab, B-cell inhibitor Rituximab (anti- CD20) and co- stimulation inhibitor abatacept). Therefore there will be a need to investigate the risk of infection during different types of immunomodulatory therapy, and to examine the need of preventive actions, including vaccinations and screening for infection.

National and international guidelines recommend pneumococcal vaccination to immunocompromised patients. The current recommendation is the 13-valent conjugated pneumococcal vaccine (PCV13), Prevenar 13®, followed by the 23-valent polysaccharide pneumococcal vaccine (PPV23), Pneumovax®. There should be at least 8 weeks between the two vaccinations.

We will investigate the serological response after vaccination with PCV13 and PPV23. The biological patients will be randomised to single or double dose PCV13. The patients receiving single dose will be randomised to boosting with PPV23 after four or six months. DMARD patients will receive single dose PCV13 and boosting with PPV23 after four months (standard of care). Follow up will be two years.

Description of the cohort

Rheumatoid arthritis patients followed at the Department of Rheumatology at either Odense University Hospital or King Christian X Hospital for Rheumatic Diseases in Gråsten.

The patients have to receive either DMARD (disease Modifying Antirheumatic Drugs) or biological therapy. Patients receiving DMARDs has to be either IgM Rheumafactor or anti-CCp positive.

Patients have to be over 18 years old.

Data and biological material

Data will be collected from:

• Survey: Status regarding prior influenza vaccination and pneumococcal vaccination and socioeconomic status.
• Biological material: Blood samples (Pneumococcal antibodies, D-vitamin, CMV serology, biobank blood samples)

Collaborating researchers and departments

Department of Rheumatology, Odense University Hospital

• Senior Consultant Hanne Lindegaard, MD, PhD

Department of Rheumatology, King Christian X Hospital for Rheumatic Diseases

• Senior Consultant Oliver Hendricks, MD, PhD

Microbiological Diagnostics & Virology, Statens Serum Institut

• Charlotte Sværke Jørgensen, MSc, PhD
• Research Scientist Bjørn Kantsø

Department of Microbiology, Odense University Hospital