The 23-valent pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis: a double-blinded, randomized, placebo-controlled trial

Abstract

BackgroundPneumococcal pneumonia is the most frequent form of pneumonia. We herein assessed the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in the prevention of pneumonia overall in rheumatoid arthritis (RA) patients at risk for infections. We hypothesized that PPSV23 vaccination is superior in preventing pneumococcal pneumonia compared with placebo in RA patients.MethodsA prospective, multicenter, double-blinded, randomized, placebo-controlled (1:1) trial was conducted across departments of rheumatology in Japanese National Hospital Organization hospitals. RA patients (n = 900) who had been treated with biological or immunosuppressive agents were randomly assigned PPSV23 or placebo (sodium chloride). The primary endpoints were the incidences of all-cause pneumonia and pneumococcal pneumonia. The secondary endpoint was death from pneumococcal pneumonia, all-cause pneumonia, or other causes. Cox regression models were used to estimate the risk of pneumonia overall for the placebo group compared with the vaccine group.ResultsSeventeen (3.7%) of 464 patients in the vaccine group and 15 (3.4%) of 436 patients in the placebo group developed pneumonia. There was no difference in the rates of pneumonia between the two study groups. The overall rate of pneumonia was 21.8 per 1000 person-years for patients with RA. The presence of interstitial pneumonia (hazard ratio: 3.601, 95% confidence interval: 1.547–8.380) was associated with an increased risk of pneumonia in RA patients.ConclusionPPSV23 does not prevent against pneumonia overall in RA patients at relative risk for infections. Our results also confirm that the presence of interstitial lung disease is associated with pneumonia in Japanese patients with RA.Trial registrationUMIN-CTR UMIN000009566. Registered 17 December 2012.

2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases

“…Two pneumococcal vaccines are now available: the 23-valent pneumococcal polysaccharide vaccine (PPSV23) and the 13-valent pneumococcal conjugate vaccine (PCV13). Regarding efficacy, a randomised double-blind trial on the clinical efficacy of PPSV23 in preventing pneumonia in RA patients did not demonstrate an increased efficacy of the vaccine over placebo 123. On the other hand, a retrospective study on the long-term effect of PPSV23 in RA patients treated with MTX showed a relative risk of 9.7 to develop pneumonia in non-vaccinated patients 124.…”

Efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases: a systematic literature review for the 2019 update of EULAR recommendations

“…Regarding efficacy of pneumococcal vaccination in AIIRD, a randomised double-blind trial on the clinical efficacy of PPSV23 in preventing pneumonia in patients with RA did not demonstrate an increased efficacy of the vaccine over placebo, emphasising the need for a more efficacious vaccine 120. In contrast, a retrospective study on the long-term effect of PPSV23 in 180 patients with RA treated with MTX showed a relative risk of 9.7 to develop pneumonia among non-vaccinated patients 121.…”

“…From the previous recommendations and up to August 2018, 34 studies53 76 81 83 84 105–133 and two meta-analyses45 77 have been published on the efficacy, immunogenicity and safety of PPSV23 and the conjugated vaccines PCV7 and PCV13, including evaluation of a combined strategy (tables 7 and 8). 106 128 133…”

The use of biological disease-modifying antirheumatic drugs for inflammatory arthritis in Korea: results of a Korean Expert Consensus

“…Given the high risk of infection in patients receiving biologic therapy, the 2015 ACR and APLAR guidelines recommended assessment of vaccination history and completion of outstanding vaccination when possible, before initiating bDMARDs. Several RCTs studied the safety and efficacy of pneumococcus, influenza, and HBV vaccination in patients receiving biologic therapy [133][134][135][136][137][138][139][140]. Biologic therapy seems to be unrelated to the side effect of the killed vaccine.…”