Vol.22 No.6

Original Article

Pneumocystis jirovecii pneumonia associated with etanercept treatment in patients with rheumatoid arthritis: a retrospective review of 15 cases and analysis of risk factors

Authors

Michi Tanaka1,2 , Ryoko Sakai1 , Ryuji Koike1,2,3 , Yukiko Komano2 , Toshihiro Nanki1,2 , Fumikazu Sakai4 , Haruhito Sugiyama5 , Hidekazu Matsushima6 , Toshihisa Kojima7 , Shuji Ohta8 , Yoji Ishibe9 , Takuya Sawabe10, Yasuhiro Ota11, Kazuhisa Ohishi12, Hajime Miyazato13, Yoshinori Nonomura2, Kazuyoshi Saito14, Yoshiya Tanaka14, Hayato Nagasawa15, Tsutomu Takeuchi16, Ayako Nakajima 17, Hideo Ohtsubo18, Makoto Onishi19, Yoshinori Goto20, Hiroaki Dobashi21, Nobuyuki Miyasaka2, Masayoshi Harigai1,2

  • Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
  • Department of Medicine and Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
  • Clinical Research Center, Tokyo Medical and Dental University Hospital, Tokyo, Japan
  • Department of Diagnostic Radiology, International Medical Center, Saitama Medical University, Saitama, Japan
  • National Center for Global Health and Medicine, Tokyo, Japan
  • Saitama Red Cross Hospital, Saitama, Japan
  • Department of Orthopedic Surgery, Nagoya University School of Medicine, Nagoya, Japan
  • Hitachi Ltd., Taga General Hospital, Hitachi, Japan
  • Saijo Central Hospital, Saijo, Japan
  • Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan
  • Yasuhiro Clinic, Hamamatsu, Japan
  • Hamamatsu Medical Center, Hamamatsu, Japan
  • Shunan Memorial Hospital, Yamaguchi, Japan
  • The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
  • Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
  • Division of Rheumatology, Department of Internal Medicine, Keio University, Tokyo, Japan
  • Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan
  • Japanese Red Cross Society Kagoshima Hospital, Kagoshima, Japan
  • Center for Rheumatic Disease, Dohogo Spa Hospital, Matsuyama, Japan
  • Goto Medical Clinic, Hamamatsu, Japan
  • Division of Endocrinology and Metabolism, Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan
Received:

11 January 2012

Accepted:

1 February 2012

Published online:

22 February 2012

Full Text

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Abstract

Objectives The association of anti-tumor necrosis factor therapy with opportunistic infections in rheumatoid arthritis (RA) patients has been reported. The goal of this study was to clarify the clinical characteristics and the risk factors of RA patients who developed Pneumocystis jirovecii pneumonia (PCP) during etanercept therapy.
Methods We conducted a multicenter, case-control study in which 15 RA patients who developed PCP were compared with 74 RA patients who did not develop PCP during etanercept therapy.
Results PCP developed within 26 weeks following the first injection of etanercept in 86.7% of the patients. All PCP patients presented with a rapid and severe clinical course and the overall mortality was 6.7%. Independent risk factors were identified using multivariate analysis and included age ?65 years [hazard ratio (HR) 3.35, p =0.037], coexisting lung disease (HR 4.48, p = 0.009), and concomitant methotrexate treatment (HR 4.68, p = 0.005). In patients having a larger number of risk factors, the cumulative probability of developing PCP was significantly higher (p<0.001 for patients with two or more risk factors vs. those with no risk factor, and p = 0.001 for patients with one risk factor vs. those with no risk factor).
Conclusion Physicians must consider the possibility of PCP developing during etanercept therapy in RA patients, particularly if one or more risk factors are present.

Key words

Pneumocystis jirovecii pneumonia - Rheumatoid arthritis - Etanercept - Anti-TNF therapy - Opportunistic infection