title: The 23-valent pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis: a double-blinded, randomized, placebo-controlled trial.
abstract: Pneumococcal 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.
  
  
  
  A 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.
  
  
  
  Seventeen (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.
  
  
  
  PPSV23 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.
  
  
  
  UMIN-CTR UMIN000009566 . Registered 17 December 2012.
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Yasumori
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Public Health and Epidemiology, Meiji Pharmaceutical University, Noshio 2-522-1, Kiyose, Tokyo, 204-8588, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Akazawa
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita, Osaka, 565-8563, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akeda
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Tohma
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Hirano
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Ideguchi
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Matsumura
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Miyamura
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Mori
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukui
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Iwanaga
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Jiuchi
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Kozuru
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsutani
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Kouichirou
authors.initials: K
authors.lastname: Saisyo
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suenaga
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Katayama
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ichikawa
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Infectious Diseases Surveillance Center, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku, Tokyo, 162-8640, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Oishi
authors.affiliation: Japanese National Hospital Organization (NHO) (Evidence-based Medicine Study Group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan. migita@fmu.ac.jp.|Department of Rheumatology, Fukushima Medical University, Hikarigaoka 1, Fukushima, 960-1295, Japan. migita@fmu.ac.jp.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D022242:Pneumococcal Vaccines / Q000276:immunology / Q000627:therapeutic use*; D011018:Pneumonia, Pneumococcal / Q000150:complications / Q000382:microbiology / Q000517:prevention & control*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000276:immunology / Q000502:physiology
chemical_list: C414006:23-valent pneumococcal capsular polysaccharide vaccine; D022242:Pneumococcal Vaccines
keywords: Interstitial lung disease; Pneumococcal polysaccharide vaccine; Pneumonia; Rheumatoid arthritis