Multicenter Study

. 2020 Apr 7;22(1):72.

doi: 10.1186/s13075-020-02171-6.

Associated factors of poor treatment outcomes in patients with giant cell arteritis: clinical implication of large vessel lesions

Takahiko Sugihara^{1

2

3}, Hitoshi Hasegawa⁴, Haruhito A Uchida⁵, Hajime Yoshifuji⁶, Yoshiko Watanabe⁷, Eisuke Amiya⁸, Yasuhiro Maejima⁹, Masanori Konishi⁹, Yohko Murakawa¹⁰, Noriyoshi Ogawa¹¹, Shunsuke Furuta¹², Yasuhiro Katsumata¹³, Yoshinori Komagata¹⁴, Taio Naniwa^{15

16}, Takahiro Okazaki^{17

18}, Yoshiya Tanaka¹⁹, Tsutomu Takeuchi²⁰, Yoshikazu Nakaoka^{21

22}, Yoshihiro Arimura^{14

23}, Masayoshi Harigai¹³, Mitsuaki Isobe^{9

24}; Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS)

Collaborators, Affiliations

Collaborators

Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS):
Shigeto Kobayashi, Tetsuya Horita, Hiroaki Dobashi, Eri Muso, Atsushi Komatsuda, Satoshi Ito, Kazuo Tanemoto, Hiroshi Akazawa, Issei Komuro, Koichi Amano, Atsushi Kawakami, Takashi Wada, Taichi Hayashi, Shinichi Takeda

Affiliations

¹ Department of Lifetime Clinical Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. sugihara.lci@tmd.ac.jp.
² Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. sugihara.lci@tmd.ac.jp.
³ Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan. sugihara.lci@tmd.ac.jp.
⁴ Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Matsuyama, Ehime, Japan.
⁵ Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
⁶ Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁷ First Department of Physiology, Kawasaki Medical School, Kurashiki, Japan.
⁸ Department of Cardiovascular Medicine, Graduate School of Medicine, Department of Therapeutic Strategy for Heart Failure, The University of Tokyo, Tokyo, Japan.
⁹ Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
¹⁰ Department of Rheumatology, Shimane University Faculty of Medicine, Izumo, Japan.
¹¹ Department of Internal Medicine 3, Hamamatsu University School of Medicine, Hamamatsu, Japan.
¹² Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan.
¹³ Department of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
¹⁴ Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan.
¹⁵ Division of Rheumatology, Department of Internal Medicine, Nagoya City University Hospital, Nagoya, Japan.
¹⁶ Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
¹⁷ Division of Rheumatology & Allergology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
¹⁸ National Hospital Organization, Shizuoka Medical Center, Shimizu, Japan.
¹⁹ The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
²⁰ Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
²¹ Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
²² Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan.
²³ Kichijoji Asahi Hospital, Tokyo, Japan.
²⁴ Sakakibara Heart Institute, Tokyo, Japan.

PMID: 32264967
PMCID: PMC7137303
DOI: 10.1186/s13075-020-02171-6

Multicenter Study

Associated factors of poor treatment outcomes in patients with giant cell arteritis: clinical implication of large vessel lesions

Takahiko Sugihara et al. Arthritis Res Ther. 2020.

. 2020 Apr 7;22(1):72.

doi: 10.1186/s13075-020-02171-6.

Authors

Collaborators

Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS):
Shigeto Kobayashi, Tetsuya Horita, Hiroaki Dobashi, Eri Muso, Atsushi Komatsuda, Satoshi Ito, Kazuo Tanemoto, Hiroshi Akazawa, Issei Komuro, Koichi Amano, Atsushi Kawakami, Takashi Wada, Taichi Hayashi, Shinichi Takeda

Affiliations

¹ Department of Lifetime Clinical Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. sugihara.lci@tmd.ac.jp.
² Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. sugihara.lci@tmd.ac.jp.
³ Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan. sugihara.lci@tmd.ac.jp.
⁴ Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Matsuyama, Ehime, Japan.
⁵ Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
⁶ Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁷ First Department of Physiology, Kawasaki Medical School, Kurashiki, Japan.
⁸ Department of Cardiovascular Medicine, Graduate School of Medicine, Department of Therapeutic Strategy for Heart Failure, The University of Tokyo, Tokyo, Japan.
⁹ Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
¹⁰ Department of Rheumatology, Shimane University Faculty of Medicine, Izumo, Japan.
¹¹ Department of Internal Medicine 3, Hamamatsu University School of Medicine, Hamamatsu, Japan.
¹² Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan.
¹³ Department of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
¹⁴ Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan.
¹⁵ Division of Rheumatology, Department of Internal Medicine, Nagoya City University Hospital, Nagoya, Japan.
¹⁶ Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
¹⁷ Division of Rheumatology & Allergology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
¹⁸ National Hospital Organization, Shizuoka Medical Center, Shimizu, Japan.
¹⁹ The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
²⁰ Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
²¹ Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
²² Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan.
²³ Kichijoji Asahi Hospital, Tokyo, Japan.
²⁴ Sakakibara Heart Institute, Tokyo, Japan.

PMID: 32264967
PMCID: PMC7137303
DOI: 10.1186/s13075-020-02171-6

Abstract

Background: Relapses frequently occur in giant cell arteritis (GCA), and long-term glucocorticoid therapy is required. The identification of associated factors with poor treatment outcomes is important to decide the treatment algorithm of GCA.

Methods: We enrolled 139 newly diagnosed GCA patients treated with glucocorticoids between 2007 and 2014 in a retrospective, multi-center registry. Patients were diagnosed with temporal artery biopsy, 1990 American College of Rheumatology classification criteria, or large vessel lesions (LVLs) detected by imaging based on the modified classification criteria. Poor treatment outcomes (non-achievement of clinical remission by week 24 or relapse during 52 weeks) were evaluated. Clinical remission was defined as the absence of clinical signs and symptoms in cranial and large vessel areas, polymyalgia rheumatica (PMR), and elevation of C-reactive protein (CRP) levels. A patient was determined to have a relapse if he/she had either one of the signs and symptoms that newly appeared or worsened after achieving clinical remission. Re-elevation of CRP without clinical manifestations was considered as a relapse if other causes such as infection were excluded and the treatment was intensified. Associated factors with poor treatment outcomes were analyzed by using the Cox proportional hazard model.

Results: Cranial lesions, PMR, and LVLs were detected in 77.7%, 41.7%, and 52.5% of the enrolled patients, respectively. Treatment outcomes were evaluated in 119 newly diagnosed patients who were observed for 24 weeks or longer. The mean initial dose of prednisolone was 0.76 mg/kg/day, and 29.4% received any concomitant immunosuppressive drugs at baseline. Overall, 41 (34.5%) of the 119 patients had poor treatment outcomes; 13 did not achieve clinical remission by week 24, and 28 had a relapse after achieving clinical remission. Cumulative rates of the events of poor treatment outcomes in patients with and without LVLs were 47.5% and 17.7%, respectively. A multivariable model showed the presence of LVLs at baseline was significantly associated with poor treatment outcomes (adjusted hazard ratio [HR] 3.54, 95% CI 1.52-8.24, p = 0.003). Cranial lesions and PMR did not increase the risk of poor treatment outcomes.

Conclusion: The initial treatment intensity in the treatment algorithm of GCA could be determined based upon the presence or absence of LVLs detected by imaging at baseline.

Keywords: Giant cell arteritis; Glucocorticoid therapy; Large vessel lesions; Poor treatment outcomes; Relapse; Remission.

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Conflict of interest statement

TS has received research grants and/or honoraria from Abbvie Japan Co., Ltd., AsahiKASEI Co., Ltd.; Astellas Pharma Inc.; Ayumi Pharmaceutical; Bristol Myers Squibb K.K.; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo; Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Co.; Ono Pharmaceutical; Pfizer Japan, Inc.; Takeda Pharmaceutical Co., Ltd.; and UCB Japan Co., Ltd. Tokyo Medical and Dental University received unrestricted research grants from Department of Lifetime Clinical Immunology from Ayumi Pharmaceutical Corporation; Chugai Pharmaceutical Co., Ltd.; CSL Behring K.K.; Japan Blood Products Organization; and UCB Japan Co., Ltd. HH has received honoraria from Chugai Pharmaceutical Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Mitsubishi-Tanabe Pharma Co.; Astellas Pharma Inc.; Bristol Myers Squibb K.K.; Pfizer Japan Inc.; Eli Lilly Japan K.K.; AsahiKASEI Co., Ltd.; Teijin Pharma Ltd.; and Abbvie Japan Co., Ltd. HAU belongs to the Department of Chronic Kidney Disease and Cardiovascular Disease which is endowed by Chugai Pharmaceutical, MSD, Boehringer Ingelheim, and Kawanishi Holdings. HY has received lecture fees from Chugai Pharmaceutical Co., Ltd. and Nihon Medi-Physics Co., Ltd. YW have received honoraria from Chugai Pharmaceutical Co., Ltd. EA belongs to the Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, University of Tokyo, which is endowed by Actelion Pharmaceuticals Japan Ltd., Otsuka Pharmaceutical, NIPRO CORPORATION, Terumo Corp., Senko Medical Instrument Mfg., Century Medical Inc., Kinetic Concepts Inc., and St. Jude Medical. EA has received honoraria from Takeda Pharmaceutical Co. Ltd., Bayer Yakuhin. Ltd., Otsuka Pharmaceutical Co., Ltd. YM has received honoraria from Chugai Pharmaceutical Co., Ltd. MK has nothing to declare. YM has received honoraria from Abbvie, Astellas, Ayumi Pharmaceutical, Bristol Myers Squibb, Chugai Pharmaceutical, Eisai Pharmaceutical, Janssen Pharmaceutical, Kissei Pharmaceutical, Nippon Kayaku, Pfizer Pharmaceutical, Takeda Pharmaceutical, and UCB Pharmaceutical and has received research grant support from Asahi Kasei Pharma, Chugai Pharmaceutical, Daiichi Sankyo, Eisai Pharmaceutical, Mitsubishi Tanabe Pharma, Nippon Kayaku, Ono Pharmaceutical, Gilead Sciences Inc., Janssen Pharmaceutical, and Teijin Pharma. NO and SF have nothing to declare. YK has received honoraria from Chugai Pharmaceutical Co., Ltd.; Glaxo-Smithkline K.K.; Sanofi K.K.; Pfizer Japan Inc.; and Asahi Kasei Pharma Corp. YK has received consulting fees from Chugai, Kyowa Hakko Kirin, Asahi Kasei, and UCB and speakers’ fees from Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Daiichi Sankyo, AbbVie, Nippon Shinyaku, and Towa. TN has received research grants and lecture fees from Chugai Pharmaceutical Co., Ltd. TO has received research grants from Chugai Pharmaceutical Co., Ltd.; Eisai Pharmaceutical.; and Actelion. YT has received consulting fees, speaking fees, and/or honoraria from Daiichi-Sankyo, Astellas, Pfizer, Mitsubishi-Tanabe, Bristol-Myers, Chugai, YL Biologics, Eli Lilly, Sanofi, Janssen, and UCB and has received research grants from Mitsubishi-Tanabe, Takeda, Bristol-Myers, Chugai, Astellas, Abbvie, MSD, Daiichi-Sankyo, Pfizer, Kyowa-Kirin, Eisai, and Ono. TT has received research grants from Astellas, Chugai, Daiichi Sankyo, Takeda, AbbVie, Asahi Kasei, Mitsubishi Tanabe, Pfizer, Eisai, AYUMI, Nippon Kayaku, and Novartis; has received consulting fees from Astra Zeneca, Eli Lilly, Novartis, Mitsubishi Tanabe, AbbVie, Nippon Kayaku, Janssen, Astellas, Taiho, Chugai, Taisho Toyama, GlaxoSmithKline, and UCB; and has served on speakers’ fees for AbbVie, Bristol-Myers Squibb, Chugai, Mitsubishi Tanabe, Pfizer, Astellas, Daiichi Sankyo, Eisai, Sanofi, Teijin, Takeda, and Novartis. YN has received research grants from Bayer Yakuhin, Ltd.; has received consulting fees and/or lecture fees and/or research grants from Chugai; has received consulting fees and/or lecture fees from AbbVie; and has received lecture fees from Astellas, Pfizer, MSD, Daiichi Sankyo, and Kowa. YA has received honoraria from Mitsubishi Tanabe Pharma Co.; Nippon Shinyaku Co., Ltd.; Chugai Pharmaceutical Co., Ltd.; Teijin Pharma, Ltd.; Asahi Kasei Corporation; AbbVie GK; F. Hoffmann-La Roche, Ltd.; GlaxoSmithKline K.K.; KYORIN Pharmaceutical Co., Ltd.; Kyowa Hakko Kirin Company, Ltd.; and Astellas Pharma Inc. MH has received research grants and/or honoraria from Abbott 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. MI has received research grants and/or honoraria from Chugai, Ono, Otsuka, Teijin, Mitsubishi-Tanabe, and Daiichi Sankyo.

Figures

**Fig. 1**
Screening, follow-up of the patients, and treatment outcomes. Clinical remission and relapse were evaluated in 119 newly diagnosed patients who were observed for more than 24 weeks. Thirteen had worsening of clinical signs and symptoms or persisted elevation of CRP and were not able to achieve clinical remission. Nine had a relapse after the achievement of clinical remission between weeks 0 and 24, and 97 had no relapse at week 24 after the achievement of clinical remission. Nineteen of the 97 had relapse between weeks 24 and 52, and 78 had no relapse at week 52 after the achievement of clinical remission. Overall, 41 had poor treatment outcomes

**Fig. 2**
Event-free curve in patients who were observed for 24 weeks or longer. a Time to poor treatment outcomes analyzed in all 119 patients who were observed for 24 weeks or longer. Patients who did not achieve clinical remission by week 24 were considered to have had an event at week 0. b Time to the first relapse in 106 patients who achieved clinical remission by week 24

See this image and copyright information in PMC

References

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Associated factors of poor treatment outcomes in patients with giant cell arteritis: clinical implication of large vessel lesions

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Associated factors of poor treatment outcomes in patients with giant cell arteritis: clinical implication of large vessel lesions

Authors

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Abstract

Conflict of interest statement

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