Observational Study

. 2019 Jan;23(1):65-75.

doi: 10.1007/s10157-018-1609-8. Epub 2018 Jun 29.

Safety and effectiveness of eculizumab for adult patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance

Affiliations

¹ Division of Nephrology and Endocrinology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
² Department of General Internal Medicine, Thrombosis and Hemostasis Center, Saitama Medical University, 38 Moroyama, Iruma-gun, Saitama, 350-0495, Japan.
³ Clinical Division of Pediatrics, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
⁴ Department of Tumor Immunology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan.
⁵ Department of Pediatrics, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanasawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
⁶ Department of Pediatrics, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto cho 3-chome, Tokushima, 770-8503, Japan.
⁷ Department of Nephrology and Rheumatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.
⁸ Department of Blood Transfusion Medicine, Nara Medical University, 840 Shijyo-cho, Kashihara, Nara, 634-8522, Japan.
⁹ Renal Replacement Therapy, Division of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
¹⁰ Alexion Pharma GK, 1-18-14 Ebisu, Shibuya-ku, Tokyo, 150-0013, Japan.
¹¹ Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
¹² Japanese Red Cross Kinki Block Blood Center, 7-5-17, Saitoasagi, Ibaraki, Osaka, 567-0085, Japan.
¹³ Department of Nephrology, Saitama Medical University, 38 Moroyama, Iruma-gun, Saitama, 350-0495, Japan. hirookda@saitama-med.ac.jp.

PMID: 29959568
PMCID: PMC6344388
DOI: 10.1007/s10157-018-1609-8

Observational Study

Safety and effectiveness of eculizumab for adult patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance

Hideki Kato et al. Clin Exp Nephrol. 2019 Jan.

. 2019 Jan;23(1):65-75.

doi: 10.1007/s10157-018-1609-8. Epub 2018 Jun 29.

Authors

Affiliations

¹ Division of Nephrology and Endocrinology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
² Department of General Internal Medicine, Thrombosis and Hemostasis Center, Saitama Medical University, 38 Moroyama, Iruma-gun, Saitama, 350-0495, Japan.
³ Clinical Division of Pediatrics, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
⁴ Department of Tumor Immunology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan.
⁵ Department of Pediatrics, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanasawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
⁶ Department of Pediatrics, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto cho 3-chome, Tokushima, 770-8503, Japan.
⁷ Department of Nephrology and Rheumatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.
⁸ Department of Blood Transfusion Medicine, Nara Medical University, 840 Shijyo-cho, Kashihara, Nara, 634-8522, Japan.
⁹ Renal Replacement Therapy, Division of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
¹⁰ Alexion Pharma GK, 1-18-14 Ebisu, Shibuya-ku, Tokyo, 150-0013, Japan.
¹¹ Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
¹² Japanese Red Cross Kinki Block Blood Center, 7-5-17, Saitoasagi, Ibaraki, Osaka, 567-0085, Japan.
¹³ Department of Nephrology, Saitama Medical University, 38 Moroyama, Iruma-gun, Saitama, 350-0495, Japan. hirookda@saitama-med.ac.jp.

PMID: 29959568
PMCID: PMC6344388
DOI: 10.1007/s10157-018-1609-8

Abstract

Background: Eculizumab has been available for the treatment of atypical hemolytic-uremic syndrome (aHUS) in Japan since 2013. To assess safety and effectiveness of eculizumab in adult aHUS patients in the real-life setting, we performed interim analysis of a post-marketing surveillance mandated by Japanese regulations.

Methods: This study enrolled any patient who was diagnosed with TMA excluding Shiga toxin-producing Escherichia coli-HUS or thrombotic thrombocytopenic purpura based on Japanese clinical guide published in 2013 as inclusion criteria and treated with eculizumab. Although the term aHUS was redefined to denote only complement-mediated HUS in the guide revised in 2016, the patients with TMA caused by other causes (secondary TMA) were included. Patient outcomes and safety were evaluated at 6 months, 12 months, and annually thereafter.

Results: Thirty-three patients with aHUS and 27 patients with secondary TMA were enrolled. Median treatment duration of aHUS was 24weeks. Complement genes variants were detected in 11 of 18 patients with aHUS (61.1%). Among the 29 aHUS patients with available baseline data, platelet count (PLT), lactic dehydrogenase and serum creatinine (SCr) improved within 1-month after eculizumab initiation. TMA event-free status, complete TMA response, PLT normalization, and SCr decrease were achieved in 67.9% (19/28), 27.8% (5/18), 56.5% (13/23), and 57.1% (16/28) of patients, respectively. Thirty-three and 11 adverse reactions were observed in patients with aHUS (13/33 patients) and secondary TMA (6/27 patients), respectively.

Conclusions: This interim analysis confirmed the acceptable safety profile and effectiveness of eculizumab for Japanese adult aHUS patients in real-world settings.

Keywords: Atypical hemolytic–uremic syndrome; C5 inhibitor; Complement; Eculizumab; Post-marketing surveillance.

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Conflict of interest statement

Conflict of interest

Employment: Takahisa Matsuda and Akihiko Shimono (Alexion Pharma GK), Advisory role: Yoshitaka Miyakawa (Ablynx, Chugai Pharmaceutical Co., Ltd., FUJIFILM Pharma Co., Ltd, Novartis Pharmaceuticals and Zenyaku Kogyo Co., Ltd.), Stock ownership: Yoshitaka Miyakawa (Preventive Medicine), Patent royalties: Yoshihiro Fujimura (Alfresa Pharma Corporation), Honoraria: Yoshihiko Hidaka, Norimitsu Inoue, Shuichi Ito, Shinya Kaname, Hideki Kato and Masaomi Nangaku (Alexion Pharma GK), Masanori Matsumoto (Alexion Pharma GK and Asahi Kasei Pharma Corporation), Hirokazu Okada (Alexion Pharma GK and Kyowa Hakko Kirin Co. Ltd.), Yoshitaka Miyakawa (Alexion Pharma GK, Bayer Yakuhin, Ltd., Baxalta Japan Limited, Bioverativ, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company Limited, Kyowa Hakko Kirin Co. Ltd., Novartis Pharmaceuticals, Teijin Pharma Limited and Zenyaku Kogyo Co., Ltd.), Shoichi Maruyama (Alexion Pharma GK, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company Limited, Kyowa Hakko Kirin Co. Ltd., Mochida Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., and Sumitomo Dainippon Pharma Co., Ltd.), Research funding: Shoichi Maruyama (Sanwa Kagaku Kenkyusho Co., Ltd.) and Masanori Matsumoto (Bayer Yakuhin, Ltd., Baxalta Japan Limited and Chugai Pharmaceutical Co., Ltd.), Subsidies: Masaomi Nangaku (Alexion Pharma GK), Shuichi Ito (Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd. and Pfizer Japan Inc.), Shoichi Maruyama (Alexion Pharma GK, Asahi Kasei Pharma Corporation, Astellas Pharma Inc., Baxter, Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company Limited, Kissei Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co. Ltd., Mitsubishi Tanabe Pharma, Mochida Pharmaceutical Co. Ltd., MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., ROHTO Pharmaceutical Co.,Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited and Torii Pharmaceutical Co.,Ltd) and Hirokazu Okada (Astellas Pharma Inc., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company Limited., Kyowa Hakko Kirin Co. Ltd., Mitsubishi Tanabe Pharma, MSD K.K., Nippon Boehringer Ingelheim Co., Novartis Pharmaceuticals, Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited and Torii Pharmaceutical Co.,Ltd.), Endowed departments by commercial entities: Masashi Mizuno (Baxter Japan).

Figures

**Fig. 1**
The level of platelet count, LDH and Serum creatinine during eculizumab treatment of aHUS patients. a PLT was significantly improved from 1week of eculizumab initiation in aHUS (complement-mediated HUS) patients. Changes from baseline were compared using the paired t test. *P < 0.05, **P < 0.01, ***P < 0.001 vs eculizumab initiation. b LDH was significantly improved from 1week of eculizumab initiation in aHUS (complement-mediated HUS) patients. Changes from baseline were compared using the paired t test. *P < 0.05, **P < 0.01, ***P < 0.001 vs eculizumab initiation. c SCr was significantly improved from 4 weeks of eculizumab initiation in aHUS (complement-mediated HUS) patients. Changes from baseline were compared using the paired t test. *P < 0.05, vs eculizumab initiation

See this image and copyright information in PMC

References

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Safety and effectiveness of eculizumab for adult patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance

Affiliations

Safety and effectiveness of eculizumab for adult patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance

Authors

Affiliations

Abstract

Conflict of interest statement

Conflict of interest

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Miscellaneous