Hayato Yamazaki1, Ryoko Sakai1, Ryuji Koike1, Yasunari Miyazaki1, Michi Tanaka1, Toshihiro Nanki1, Kaori Watanabe1, Shinsuke Yasuda1, Takashi Kurita1, Yuko Kaneko1, Yoshiya Tanaka1, Yasuhiko Nishioka1, Yoshinari Takasaki1, Kenji Nagasaka1, Hayato Nagasawa1, Shigeto Tohma1, Makoto Dohi1, Takahiko Sugihara1, Haruhito Sugiyama1, Yasushi Kawaguchi1, Naohiko Inase1, Sae Ochi1, Hiroyuki Hagiyama1, Hitoshi Kohsaka1, Nobuyuki Miyasaka1, Masayoshi Harigai. 1. From the Department of Pharmacovigilance, Department of Medicine and Rheumatology, and Department of Integrated Pulmonology, Graduate School of Medical and Dental Sciences, the Clinical Research Center, and the Global Center of Excellence (GCOE) Program, and the International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University (TMDU); Division of Rheumatology, and Department of Internal Medicine, Keio University School of Medicine, Tokyo; Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo; Department of Rheumatology, Tokyo Metropolitan Geriatric Hospital; Department of Respiratory Medicine, National Center for Global Health and Medicine; Institute of Rheumatology, Tokyo Women's Medical University; Department of Rheumatology, Tokyo Metropolitan Bokutoh Hospital, Tokyo; Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo; The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu; Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima; Department of Rheumatology, Ome Municipal General Hospital, Ome; Department of Rheumatology/Clinical Immunology, Saitama Medical Center, Saitama Medical University, Kawagoe; Department of Rheumatology, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, National Hospital Organization, Sagamihara; and the Department of Rheumatology, Yokohama City Minato Red Cross Hospital, Yokohama, Japan.H. Yamazaki, MD; R. Sakai, PhD; M. Tanaka, MD, PhD; T. Nanki, MD, PhD; K. Watanabe, MD, PhD; M. Harigai, MD, PhD, Professor, Department of Pharmacovigilance, and Department of Medicine and Rheumatology, Graduate School of Medical and Dental Sciences, TMDU; R. Koike, MD, PhD, Departme
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.
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.