Assessment of risks of pulmonary infection during 12 months following immunosuppressive treatment for active connective tissue diseases

A large-scale prospective cohort study

Hayato Yamazaki, Ryoko Sakai, Ryuji Koike, Yasunari Miyazaki, Michi Tanaka, Toshihiro Nanki, Kaori Watanabe, Shinsuke Yasuda, Takashi Kurita, Yuko Kaneko, Yoshiya Tanaka, Yasuhiko Nishioka, Yoshinari Takasaki, Kenji Nagasaka, Hayato Nagasawa, Shigeto Tohma, Makoto Dohi, Takahiko Sugihara, Haruhito Sugiyama, Yasushi Kawaguchi & 6 others Naohiko Inase, Sae Ochi, Hiroyuki Hagiyama, Hitoshi Kohsaka, Nobuyuki Miyasaka, Masayoshi Harigai

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective. Pulmonary infections (PI) are leading causes of death in patients with connective tissue diseases (CTD). The PREVENT study (Pulmonary infections in patients REceiving immunosuppressiVE treatmeNT for CTD) assessed risk of PI in patients with active CTD in the contemporary era of advanced immunosuppressive therapy. Methods. In patients who started corticosteroids (n = 763), conventional immunosuppressants or biologics for active CTD were enrolled. Clinical and laboratory data, usage of drugs, and occurrence of PI were collected for 12 months. Baseline risk factors were investigated using Cox regression analysis. A nested case-control (NCC) study was performed with 1:2 matched case-control pairs to assess the risk for each drug category. Results. During the observation period, 32 patients died (4.2%) and 66 patients were lost to followup (8.6%). Patients with PI (n = 61, 8%) had a significantly worse accumulated survival rate than patients without (p ≤ 0.01). Cox hazard regression analysis using baseline data showed that these factors were significantly associated with PI: age > 65 years (HR 3.87, 95% CI 2.22-6.74), > 20 pack-years of smoking (2.63, 1.37-5.04), higher serum creatinine level (1.21, 1.05-1.41 per 1.0 mg/dl increase), and maximum prednisolone (PSL) dose during the first 2 weeks of treatment (2.81, 1.35-5.86 per 1.0 mg/kg/day increase). Logistic regression analysis by an NCC study revealed that maximum PSL dose within 14 days before PI (OR 4.82, 95% CI 1.36-17.01 per 1.0 mg/dl increase; 2.57, 1.28-5.16 if > 0.5 mg/kg/day) was significantly associated with the events, while other immunosuppressants were not. Conclusion. Physicians should be aware of the higher risks for corticosteroids of PI than other immunosuppressants and assess these risk factors before immunosuppressive treatment, to prevent PI.

Original languageEnglish
Pages (from-to)614-622
Number of pages9
JournalJournal of Rheumatology
Volume42
Issue number4
DOIs
Publication statusPublished - 2015 Apr 1

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Connective Tissue Diseases
Immunosuppressive Agents
Cohort Studies
Prospective Studies
Lung
Infection
Therapeutics
Regression Analysis
Prednisolone
Case-Control Studies
Adrenal Cortex Hormones
Biological Products
Pharmaceutical Preparations
Cause of Death
Creatinine
Survival Rate
Logistic Models
Smoking
Observation
Physicians

Keywords

  • Cohort studies
  • Connective tissue diseases
  • Corticosteroids
  • Immunosuppressive agents
  • Infection

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

Assessment of risks of pulmonary infection during 12 months following immunosuppressive treatment for active connective tissue diseases : A large-scale prospective cohort study. / Yamazaki, Hayato; Sakai, Ryoko; Koike, Ryuji; Miyazaki, Yasunari; Tanaka, Michi; Nanki, Toshihiro; Watanabe, Kaori; Yasuda, Shinsuke; Kurita, Takashi; Kaneko, Yuko; Tanaka, Yoshiya; Nishioka, Yasuhiko; Takasaki, Yoshinari; Nagasaka, Kenji; Nagasawa, Hayato; Tohma, Shigeto; Dohi, Makoto; Sugihara, Takahiko; Sugiyama, Haruhito; Kawaguchi, Yasushi; Inase, Naohiko; Ochi, Sae; Hagiyama, Hiroyuki; Kohsaka, Hitoshi; Miyasaka, Nobuyuki; Harigai, Masayoshi.

In: Journal of Rheumatology, Vol. 42, No. 4, 01.04.2015, p. 614-622.

Research output: Contribution to journalArticle

Yamazaki, H, Sakai, R, Koike, R, Miyazaki, Y, Tanaka, M, Nanki, T, Watanabe, K, Yasuda, S, Kurita, T, Kaneko, Y, Tanaka, Y, Nishioka, Y, Takasaki, Y, Nagasaka, K, Nagasawa, H, Tohma, S, Dohi, M, Sugihara, T, Sugiyama, H, Kawaguchi, Y, Inase, N, Ochi, S, Hagiyama, H, Kohsaka, H, Miyasaka, N & Harigai, M 2015, 'Assessment of risks of pulmonary infection during 12 months following immunosuppressive treatment for active connective tissue diseases: A large-scale prospective cohort study', Journal of Rheumatology, vol. 42, no. 4, pp. 614-622. https://doi.org/10.3899/jrheum.140778
Yamazaki, Hayato ; Sakai, Ryoko ; Koike, Ryuji ; Miyazaki, Yasunari ; Tanaka, Michi ; Nanki, Toshihiro ; Watanabe, Kaori ; Yasuda, Shinsuke ; Kurita, Takashi ; Kaneko, Yuko ; Tanaka, Yoshiya ; Nishioka, Yasuhiko ; Takasaki, Yoshinari ; Nagasaka, Kenji ; Nagasawa, Hayato ; Tohma, Shigeto ; Dohi, Makoto ; Sugihara, Takahiko ; Sugiyama, Haruhito ; Kawaguchi, Yasushi ; Inase, Naohiko ; Ochi, Sae ; Hagiyama, Hiroyuki ; Kohsaka, Hitoshi ; Miyasaka, Nobuyuki ; Harigai, Masayoshi. / Assessment of risks of pulmonary infection during 12 months following immunosuppressive treatment for active connective tissue diseases : A large-scale prospective cohort study. In: Journal of Rheumatology. 2015 ; Vol. 42, No. 4. pp. 614-622.
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abstract = "Objective. Pulmonary infections (PI) are leading causes of death in patients with connective tissue diseases (CTD). The PREVENT study (Pulmonary infections in patients REceiving immunosuppressiVE treatmeNT for CTD) assessed risk of PI in patients with active CTD in the contemporary era of advanced immunosuppressive therapy. Methods. In patients who started corticosteroids (n = 763), conventional immunosuppressants or biologics for active CTD were enrolled. Clinical and laboratory data, usage of drugs, and occurrence of PI were collected for 12 months. Baseline risk factors were investigated using Cox regression analysis. A nested case-control (NCC) study was performed with 1:2 matched case-control pairs to assess the risk for each drug category. Results. During the observation period, 32 patients died (4.2{\%}) and 66 patients were lost to followup (8.6{\%}). Patients with PI (n = 61, 8{\%}) had a significantly worse accumulated survival rate than patients without (p ≤ 0.01). Cox hazard regression analysis using baseline data showed that these factors were significantly associated with PI: age > 65 years (HR 3.87, 95{\%} CI 2.22-6.74), > 20 pack-years of smoking (2.63, 1.37-5.04), higher serum creatinine level (1.21, 1.05-1.41 per 1.0 mg/dl increase), and maximum prednisolone (PSL) dose during the first 2 weeks of treatment (2.81, 1.35-5.86 per 1.0 mg/kg/day increase). Logistic regression analysis by an NCC study revealed that maximum PSL dose within 14 days before PI (OR 4.82, 95{\%} CI 1.36-17.01 per 1.0 mg/dl increase; 2.57, 1.28-5.16 if > 0.5 mg/kg/day) was significantly associated with the events, while other immunosuppressants were not. Conclusion. Physicians should be aware of the higher risks for corticosteroids of PI than other immunosuppressants and assess these risk factors before immunosuppressive treatment, to prevent PI.",
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author = "Hayato Yamazaki and Ryoko Sakai and Ryuji Koike and Yasunari Miyazaki and Michi Tanaka and Toshihiro Nanki and Kaori Watanabe and Shinsuke Yasuda and Takashi Kurita and Yuko Kaneko and Yoshiya Tanaka and Yasuhiko Nishioka and Yoshinari Takasaki and Kenji Nagasaka and Hayato Nagasawa and Shigeto Tohma and Makoto Dohi and Takahiko Sugihara and Haruhito Sugiyama and Yasushi Kawaguchi and Naohiko Inase and Sae Ochi and Hiroyuki Hagiyama and Hitoshi Kohsaka and Nobuyuki Miyasaka and Masayoshi Harigai",
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T1 - Assessment of risks of pulmonary infection during 12 months following immunosuppressive treatment for active connective tissue diseases

T2 - A large-scale prospective cohort study

AU - Yamazaki, Hayato

AU - Sakai, Ryoko

AU - Koike, Ryuji

AU - Miyazaki, Yasunari

AU - Tanaka, Michi

AU - Nanki, Toshihiro

AU - Watanabe, Kaori

AU - Yasuda, Shinsuke

AU - Kurita, Takashi

AU - Kaneko, Yuko

AU - Tanaka, Yoshiya

AU - Nishioka, Yasuhiko

AU - Takasaki, Yoshinari

AU - Nagasaka, Kenji

AU - Nagasawa, Hayato

AU - Tohma, Shigeto

AU - Dohi, Makoto

AU - Sugihara, Takahiko

AU - Sugiyama, Haruhito

AU - Kawaguchi, Yasushi

AU - Inase, Naohiko

AU - Ochi, Sae

AU - Hagiyama, Hiroyuki

AU - Kohsaka, Hitoshi

AU - Miyasaka, Nobuyuki

AU - Harigai, Masayoshi

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Objective. Pulmonary infections (PI) are leading causes of death in patients with connective tissue diseases (CTD). The PREVENT study (Pulmonary infections in patients REceiving immunosuppressiVE treatmeNT for CTD) assessed risk of PI in patients with active CTD in the contemporary era of advanced immunosuppressive therapy. Methods. In patients who started corticosteroids (n = 763), conventional immunosuppressants or biologics for active CTD were enrolled. Clinical and laboratory data, usage of drugs, and occurrence of PI were collected for 12 months. Baseline risk factors were investigated using Cox regression analysis. A nested case-control (NCC) study was performed with 1:2 matched case-control pairs to assess the risk for each drug category. Results. During the observation period, 32 patients died (4.2%) and 66 patients were lost to followup (8.6%). Patients with PI (n = 61, 8%) had a significantly worse accumulated survival rate than patients without (p ≤ 0.01). Cox hazard regression analysis using baseline data showed that these factors were significantly associated with PI: age > 65 years (HR 3.87, 95% CI 2.22-6.74), > 20 pack-years of smoking (2.63, 1.37-5.04), higher serum creatinine level (1.21, 1.05-1.41 per 1.0 mg/dl increase), and maximum prednisolone (PSL) dose during the first 2 weeks of treatment (2.81, 1.35-5.86 per 1.0 mg/kg/day increase). Logistic regression analysis by an NCC study revealed that maximum PSL dose within 14 days before PI (OR 4.82, 95% CI 1.36-17.01 per 1.0 mg/dl increase; 2.57, 1.28-5.16 if > 0.5 mg/kg/day) was significantly associated with the events, while other immunosuppressants were not. Conclusion. Physicians should be aware of the higher risks for corticosteroids of PI than other immunosuppressants and assess these risk factors before immunosuppressive treatment, to prevent PI.

AB - Objective. Pulmonary infections (PI) are leading causes of death in patients with connective tissue diseases (CTD). The PREVENT study (Pulmonary infections in patients REceiving immunosuppressiVE treatmeNT for CTD) assessed risk of PI in patients with active CTD in the contemporary era of advanced immunosuppressive therapy. Methods. In patients who started corticosteroids (n = 763), conventional immunosuppressants or biologics for active CTD were enrolled. Clinical and laboratory data, usage of drugs, and occurrence of PI were collected for 12 months. Baseline risk factors were investigated using Cox regression analysis. A nested case-control (NCC) study was performed with 1:2 matched case-control pairs to assess the risk for each drug category. Results. During the observation period, 32 patients died (4.2%) and 66 patients were lost to followup (8.6%). Patients with PI (n = 61, 8%) had a significantly worse accumulated survival rate than patients without (p ≤ 0.01). Cox hazard regression analysis using baseline data showed that these factors were significantly associated with PI: age > 65 years (HR 3.87, 95% CI 2.22-6.74), > 20 pack-years of smoking (2.63, 1.37-5.04), higher serum creatinine level (1.21, 1.05-1.41 per 1.0 mg/dl increase), and maximum prednisolone (PSL) dose during the first 2 weeks of treatment (2.81, 1.35-5.86 per 1.0 mg/kg/day increase). Logistic regression analysis by an NCC study revealed that maximum PSL dose within 14 days before PI (OR 4.82, 95% CI 1.36-17.01 per 1.0 mg/dl increase; 2.57, 1.28-5.16 if > 0.5 mg/kg/day) was significantly associated with the events, while other immunosuppressants were not. Conclusion. Physicians should be aware of the higher risks for corticosteroids of PI than other immunosuppressants and assess these risk factors before immunosuppressive treatment, to prevent PI.

KW - Cohort studies

KW - Connective tissue diseases

KW - Corticosteroids

KW - Immunosuppressive agents

KW - Infection

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