Clinical characteristics of and risk factors for serious infection in Japanese patients within six months of remission induction therapy for antineutrophil cytoplasmic antibody-associated vasculitis registered in a nationwide, prospective, inception cohort study

Abstract

Objectives: The purpose of this study was to identify the clinical characteristics and predictors of serious infections (SIs) in the RemIT-JAV, a nationwide, prospective, inception cohort study for Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

Methods: We analyzed SIs within six months of remission induction therapy in 156 AAV patients. Hazard ratios with 95% confidence intervals (CIs) for SIs were calculated using the COX proportional hazard model.

Results: Sixty-three SIs in 42 patients were identified. The incidence rate (IR) of SIs was 87.59/100 patient-years. The median length of time to the onset of first SIs was 54 days. Hazard ratios (95%CI) for SIs were 1.97 (0.99–3.95) for age >65 years, 0.47 (0.25–0.89) for female sex, 2.11 (1.05–4.27) for the severe form of AAV, and 2.88 (1.49–5.88) for initial PSL >0.8 mg/kg/day in the first model, and 2.64 (1.39–5.01) for smoking and 3.27 (1.66–6.45) for initial PSL >0.8 mg/kg/day in the second model.

Conclusions: Lowering the IR of SIs in Japanese AAV patients is mandatory to improve the vital prognosis of these patients. For remission induction therapy of AAV patients with these risk factors, risk management of immunosuppressive treatment should be carefully considered.

Keywords:

• Antineutrophil cytoplasmic antibody-associated vasculitis
• Corticosteroid
• Inception cohort study
• Risk factors
• Safety
• Serious infection

Acknowledgments

The authors thank Keiko Hongo, Kumiko Muraki, Eri Katsuyama, Takayuki Katsuyama, Haruki Watanabe, Mariko Narazaki, Noriko Toyota, Yoshinori Matsumoto, Ryutaro Yamanaka, and Kouichi Sugiyama for their great assistance in data management and Ryoko Sakai for her contribution to the statistical analysis. The authors also thank all patients and their health care providers who participated in this study

Conflict of interest

MH has received research grants and/or honoraria from Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma, Ltd., and Pfizer Japan Inc. TF belongs to a department that is financially supported by Mitsubishi Tanabe Pharma Co., Ltd., Bristol-Myers K.K., and Eisai Co., Ltd., and has received research grants from Abbott Japan Co., Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo Pharmaceutical Co. Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co, Takeda Pharmaceutical Co., Ltd., and Pfizer Japan Inc. KA has received research grants and/or honoraria from AbbVie Japan Co. Ltd., Astellas Pharma Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co. Ltd., Mitsubishi-Tanabe Pharma Co., Pfizer Japan Inc. HM is a consultant for AbbVie and Teijin, receives speaker honoraria from Astellas, Boehringer-ingelheim, Daiichi Sankyo, Dainippon Sumitomo, Kyowa Hakko Kirin, MSD, Pfizer, Takeda, and Tanabe Mitsubishi, and receives grant support from Astellas, Boehringer-ingelheim, Daiichi Sankyo, Dainippon Sumitomo, Kowa, Kyowa Hakko Kirin, MSD, Novartis, Novo Nordisk, Ono, Otsuka, Pfizer, Taishyo-Toyama, Takeda, Teijin, and Tanabe Mitsubishi. K.W-I., K.S., M.Y, H.D., S.I., S.H., S.K., S.B., Y.A. do not have any conflict of interest to declare. This work was supported by grants from Research on Rare and Intractable Diseases, the Ministry of Health, Labor and Welfare, Japan [H23-25 nanti-ippann-004, H26 nanti-ippan-004].

Research committee of intractable vasculitis syndrome of the ministry of health, labor, and welfare of Japan

In addition to the authors, the following investigators and institutions participated in this study: Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine (Yoshinari Takasaki); Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine (Hidehiro Yamada); Department of Nephrology, Faculty of Medicine, University of Tsukuba (Kunihiro Yamagata); Department of Hemovascular and Artificial Organs, Faculty of Medicine, University of Miyazaki (Shouichi Fujimoto); Division of Nephrology, Department of Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University (Takashi Wada); Center for Nephrology and Urology, Division of Nephrology and Dialysis, Kitano Hospital, Tazuke Kofukai Medical Research Institute (Eri Muso); Department of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo (Junichi Hirahashi); Department of Rheumatology, Shimane University Faculty of Medicine (Yohko Murakawa); Department of Bioregulatory Medicine, Ehime University Graduate School of Medicine (Hitoshi Hasegawa); Jichi Medical University (Wako Yumura); Division of Nephrology, Department of Internal Medicine, Department of Cardiovascular Medicine, Kyoto Prefectural University School of Medicine (Hiroaki Matsubara); Division of Nephrology, Tokyo Medical University Hachioji Medical Center (Masaharu Yoshida); Department of Dermatology, Kitasato University School of Medicine (Kensei Katsuoka); Third Department of Internal Medicine, Division of Immunology and Rheumatology, Hamamatsu University School of Medicine, Hamamatsu (Noriyoshi Ogawa).