POS0336 PATTERNS OF LARGE-VESSEL LESIONS AND POOR TREATMENT OUTCOMES IN PATIENTS WITH LARGE-VESSEL GIANT CELL ARTERITIS
Authors: T. Sugihara, H. A. Uchida, H. Yoshifuji, Y. Maejima, T. Naniwa, Y. Katsumata, T. Okazaki, J. Ishizaki, Y. Murakawa, N. Ogawa, H. Dobashi, T. Horita, Y. Tanaka, S. Furuta, T. Takeuchi, Y. Komagata, Y. Nakaoka, M. Harigai
Journal: Annals of the Rheumatic Diseases (2021)

Background: Giant cell arteritis (GCA) is characterized by cranial symptoms and large-vessel lesions (LVL) in the aorta or its branches. We retrospectively analyzed the Japanese patients newly diagnosed as GCA between 2007 and 2014, and subsequently treated with glucocorticoid (GC). The imaging studies revealed that LVLs were observed in approximately half of the GCA patients, and the LVLs were significantly associated with the increased probability of poor treatment outcomes (1). Objectives: The objective of this study is to evaluate whether the distribution of LVLs of GCA was associated with poor treatment response. Methods: In a retrospective, multi-centric, nationwide registry of GCA patients treated with GCs between 2007 and 2014, 68 newly-diagnosed GCA with LVLs by imaging were detected. All investigators were members of Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS). Poor treatment outcomes (non-achievement of clinical remission by week 24 or relapse during 104 weeks) were primarily evaluated. Cumulative rates and median time to the first event were analyzed by the Kaplan-Meier method and the log-rank test. Associated factors with the outcomes were analyzed by using the Cox proportional hazard model. Results: The mean age was 70.5 years, and 70.6% were women. Twenty-seven (39.7%) of the 68 patients were diagnosed as having GCA by both positive temporal artery biopsy and positive imaging, and 41 (60.3%) by positive imaging. Aortic lesions were detected in 72.1% (group 2, n=49) of the 68 GCA patients with LVLs. Patients without aortic lesions were categorized into two phenotypes: large-vessel GCA with subclavian lesions (group 1, n=9) and atypical large-vessel GCA without subclavian lesions (group 3, n=10). Cranial lesions were observed in 66.7%, 55.1%, and 80.0% in the group 1, 2, and 3, respectively. The initial mean dose (SD) of prednisolone was 0.74 (0.26) mg/kg/day, and 20.6 % received methotrexate for remission induction therapy. Baseline dose of GCs and mean time to achievement of low-dose GCs (prednisolone ≤ 5 mg/day) was not significantly different among the three groups. Overall, 35 (51.5%) of the 68 patients had the event of poor treatment outcomes. Eleven patients were not able to achieve clinical remission by week 24. Relapse after achievement of clinical remission was reported in total of 24 patients; 9 between week 0 and 24, 12 between week 24 and 52, 3 between week 52 and 104. The cumulative rate of events of poor treatment outcomes over the two years was 11.1% in patients with group 1, 55.3% in those with group 2, and 88.0% in those with group 3. Mean time to events was significantly different among the three groups. Multivariable analysis showed the risk of poor treatment outcomes was likely to decrease in the group 1 (hazard ratio 0.14 [95% CI 0.02-1.03], p=0.054), while it increased in the group 3 (hazard ratio 2.22 [95% CI 1.06-4.68], p=0.035). Conclusion: The distribution of LVLs were associated with poorer treatment outcomes. A half of the patients with aortic lesions had poor treatment outcomes while subclavian arteritis without aortic lesions had better clinical outcomes. Atypical large vessel-GCA without the aortic and subclavian artery involvement was the worst prognostic phenotype of LV-GCA. Extent of LVLs by imaging should be considered when determining the treatment strategy for GCA. References: [1]Sugihara T, et al. Arthritis Res Ther. 2020;22(1):72 Acknowledgements: The authors would like to acknowledge Mitsuaki Isobe (Sakakibara Heart Institute), Yoshihiro Arimura (Kichijoji Asahi Hospital), and all the investigators in the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis (JPVAS). In addition to the authors, the following investigators and institutions participated in this study: Department of Internal Medicine, Juntendo University Koshigaya Hospital (Shigeto Kobayashi); Niigata Rheumatic Center (Satoshi Ito); Niigata Prefectural Shibata Hospital (Noriyuki Homma). Disclosure of Interests: takahiko sugihara Speakers bureau: TS has received honoraria from Abbvie Japan Co., Ltd., AsahiKASEI Co., Ltd., Astellas Pharma Inc., Ayumi Pharmaceutical, Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Mitsubishi-Tanabe Pharma Co., Ono Pharmaceutical, Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., and UCB Japan Co. Ltd., Grant/research support from: TS has received research grants from AsahiKASEI Co., Ltd., Daiichi Sankyo., and Ono Pharmaceutical., Haruhito A. Uchida Grant/research support from: HAU belongs to the Department of Chronic Kidney Disease and Cardiovascular Disease which is endowed by Chugai Pharmaceutical, MSD, Boehringer Ingelheim, and Kawanishi Holdings., Hajime Yoshifuji Speakers bureau: HY has received lecture fees from Chugai Pharmaceutical Co., Ltd. and Nihon Medi-Physics Co., Ltd., Yasuhiro Maejima Speakers bureau: YM have received honoraria from Chugai Pharmaceutical Co., Ltd.., Taio Naniwa Speakers bureau: TN has received lecture fees from Chugai Pharmaceutical Co., Ltd.., Grant/research support from: TN has received research grants from Chugai Pharmaceutical Co., Ltd.., Yasuhiro Katsumata Speakers bureau: YK has received honoraria from Chugai Pharmaceutical Co., Ltd., Glaxo-Smithkline K.K., Sanofi K.K., Pfizer Japan Inc., and Asahi Kasei Pharma Corp., Takahiro Okazaki Grant/research support from: TO has received research grants from Chugai Pharmaceutical Co., Ltd., Eisai Pharmaceutical., and Actelion, Jun Ishizaki: None declared, Yohko Murakawa Speakers bureau: 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, UCB Pharmaceutical, Grant/research support from: YM has received research grant support from Asahi Kasei Pharma, AbbVie Japan, Chugai Pharmaceutical, Daiichi Sankyo, Eisai Pharmaceutical, Mitsubishi Tanabe Pharma, Nippon Kayaku, Gilead Sciences Inc, Janssen Pharmaceutical, and Teijin Pharma., Noriyoshi Ogawa: None declared, Hiroaki Dobashi: None declared, Tetsuya Horita: None declared, Yoshiya Tanaka Speakers bureau: 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, UCB, Grant/research support from: YT has received research grants from Mitsubishi-Tanabe, Takeda, Bristol-Myers, Chugai, Astellas, Abbvie, MSD, Daiichi-Sankyo, Pfizer, Kyowa- Kirin, Eisai, Ono., Shunsuke Furuta: None declared, Tsutomu Takeuchi Speakers bureau: TT has served on speakers’ fees for AbbVie, Bristol-Myers Squibb, Chugai, Mitsubishi Tanabe, Pfizer, Astellas, Daiichi Sankyo, Eisai, Sanofi, Teijin, Takeda, and Novartis., Consultant of: TT has received consulting fees from Astra Zeneca, Eli Lilly, Novartis, Mitsubishi Tanabe, AbbVie, Nippon Kayaku, Janssen, Astellas, Taiho, Chugai, Taisho Toyama, GlaxoSmithKline, and UCB., Grant/research support from: TT has received research grants from Astellas, Chugai, Daiichi Sankyo, Takeda, AbbVie, Asahi Kasei, Mitsubishi Tanabe, Pfizer, Eisai, AYUMI, Nippon Kayaku, and Novartis., Yoshinori Komagata Speakers bureau: YK has received speakers’ fees from Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Daiichi Sankyo, AbbVie, Nippon Shinyaku, Towa., Consultant of: YK has received consulting fees from Chugai, Kyowa Hakko Kirin, Asahi Kasei, UCB, Yoshikazu Nakaoka Speakers bureau: YN has received lecture fees from Astellas, Takeda, Daiichi Sankyo, Actelion, and Japan Blood Products Organization (JB)., Consultant of: YN has received consulting fees and/or lecture fees from AbbVie and Chugai, Grant/research support from: YN has received research grants from Chugai and Bayer Yakuhin, Ltd, masayoshi harigai Speakers bureau: MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Consultant of: MH is a consultant for AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma., Grant/research support from: MH has received research grants from AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi &amp; Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd.