Assessment of Risks of Pulmonary Infection During 12 Months Following Immunosuppressive Treatment for Active Connective Tissue Diseases: A Large-scale Prospective Cohort Study

作者：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^*

来源：Journal of Rheumatology, 2015, 42(4): 614-622.

DOI：10.3899/jrheum.140778

• CONNECTIVE TISSUE DISEASES
• IMMUNOSUPPRESSIVE AGENTS
• INFECTION
• COHORT STUDIES
• CORTICOSTEROIDS

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.

• 出版日期2015-4