T. Miyamae1, T. Kawabe1, K. Nishimura2, S. Hattori2, T. Imagawa3, T. Ishii4, S. Ito2, N. Iwata5, Y. Kamata6, Y. Kamiyama2, M. Mizuta7, M. Mori8,9, A. Murase2, Y. Nakagishi7, T. Nakano10, S. Nakayamada11, T. Nozawa2, T. Ohya2, N. Okamoto12,13, K. Sato14, Y. Sugita12, S. Takei15, S. Tanaka16, Y. Tanaka17, M. Tomiita18, H. Umebayashi19, Y. Yamasaki15, N. Nishimoto20,21, S. Yokota2 1Department of Pediatric Rheumatology, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo; 2Department of Pediatrics, Yokohama City University Graduate School of Medicine; 3Infectious Diseases & Immunology, Kanagawa Children's Medical Center, Yokohama; 4Clinical Research, Education and Innovation Center, Tohoku University Hospital, Sendai; 5Department of Infection and Immunology, Aichi Children’s Health and Medical Center, Obu; 6Division of Rhematology and Clinical Immunology, Jichi Medical University, uShimotsuke-shi, Tochigi; 7Department of Pediatric Rheumatology, Hyogo Prefectual Kobe Children's Hospital, Kobe; 8Department of Lifetime Clinical Immunology, Tokyo Medical and Dental University, Tokyo; 9Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki; 10Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba; 11The First Department of Internal Medicine, Japan, University of Occupational and Environmental Health, Kitakyushu; 12Department of Pediatrics, Osaka Medical and Pharmaceutical University, Takatsuki; 13Department of Pediatrics, Osaka Rosai Hospital, Sakai; 14Division of Rheumatology and Clinical Immunology, Jichi Medical University, Shimotsuke-shi, Tochigi; 15Department of Pediatrics, Kagoshima University, Kagoshima; 16Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume; 17The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu; 18Department of Allergy and Rheumatology, Chiba Children's Hospital, Chiba; 19Deptment of Rheumatism, Infection Disease, Miyagi Children's Hospital, Sendai, 20Osaka Rheumatology Clinic; 21Department of Molecular Regulation for Intractable Diseases Institute of Medical Science, Tokyo Medical University, Osaka, Japan Correspondence: T. Miyamae

Pediatric Rheumatology 2023, 21(Suppl 2):O03

Introduction: In 2008, Tocilizumab (TCZ) was approved for systemic juvenile idiopathic arthritis (sJIA) as an intravenous formulation after its efficacy and safety were demonstrated in a clinical trial conducted in Japan between 2002 and 2008.

Objectives: This study aimed to comprehend the long-term prognosis of patients who participated in phases II (MRA011JP), III (MRA316JP), and III/IV (MRA324JP) of the clinical trial. A total of 149 participants were included in the study.

Methods: The primary endpoint of this study was the sustained frequency of TCZ administration throughout the prolonged observation period of sJIA. Secondary endpoints encompassed additional long-term prognostic determinants, such as therapeutic conditions, disease status including remission rate and clinical phenotype, complications, social adaptation, employment status, and quantification of health-related quality of life (HRQOL).

Results: Results were collected for 147 cases by April 2023. Among the 135 patients (61 male and 74 female) whose medical records were available and final diagnosis was sJIA, the median age of the study participants was 26.7 years at the time of the study, 4.3 years at the onset of sJIA, 9.2 years at the first administration of TCZ, 4.0 years from the onset to the first TCZ administration, and 9.8 years from the initiation of TCZ (all median values). Thirty-four (25.2%) were in medication-free remission, and 97 (71.9%) continued therapy. Of the 97 patients, 91 were treated with b-/ts-DMARDs. Tocilizumab was continued in 83 patients (61.5%), and six were switched to canakinumab (CAN) due to TCZ failure, side effects, or other reasons. Except for an isolated incident of sudden death, three cases resulted in a fatal outcome. Specifically, the causes of mortality were macrophage activation syndrome, sJIA-associated interstitial pneumonia, and disseminated aspergillosis. Forty-four (32.6%) transitioned from acute febrile sJIA to chronic arthritic sJIA, in which chronic arthritis was the primary pathology without systemic inflammation. Macrophage activation syndrome was developed in 33 patients (24.4%) during the clinical course. The most commonly observed complications were osteoporosis in 74 (54.8%), infection requiring hospitalization in 43 (31.8%), and hypertension in 28 (20.7%). The EQ-5D-5L score was 0.89 (mean). The final mean height was 156.6 cm for males and 144.0 cm for females, showing a significant short stature. The college/university enrollment rate was as high as 65.4%, and all but five students were employed.

Conclusion: After approximately a decade of observation, 71.9% of the patients remained under treatment, with 61.5% electing to receive TCZ. Conversion to chronic arthritic sJIA was detected in 32.6% of the patient population. Despite the presence of primary disease activity and associated complications, the level of social adjustment observed was satisfactory, implying a favorable impact of the administered treatment.

Patient Consent

Yes, I received consent

Disclosure of Interest

T. Miyamae Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: Chugai Pharma, Novartis Farma, T. Kawabe Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: none, K. Nishimura Shareholder with: none, Grant / Research Support with: Chugai Pharma, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: Novaritis Pharma, S. Hattori Shareholder with: none, Grant / Research Support with: Chugai Pharma, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: none, T. Imagawa Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: none, T. Ishii Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: Chugai Pharma, S. Ito Shareholder with: none, Grant / Research Support with: Chugai Pharma, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: Novaritis Pharma, Chugai Pharma, N. Iwata Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: ONO PHARMACEUTICAL CO., LTD., GlaxoSmithKline Plc., Y. Kamata Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: none, Y. Kamiyama Shareholder with: none, Grant / Research Support with: Chugai Pharma, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: none, M. Mizuta Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: Novaritis Pharma, M. Mori Shareholder with: none, Grant / Research Support with: I belong to the department that is financially supported by Chugai, UCB Japan, CSL Behring, Abbvie Japan, Japan Blood Products Organization, AYUMI, Nippon Kayaku, and Asahi-Kasei. , Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: I have received lecture fees from MSD, Chugai, UCB Japan, Abbvie Japan, Japan Blood Products Organization, AYUMI, and Asahi-Kasei., A. Murase Shareholder with: none, Grant / Research Support with: Chugai Pharma, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: none, Y. Nakagishi Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: CHUGAI PHARMACEUTICAL CO.,LTD. Novartis Pharma K.K. AstraZeneca plc, T. Nakano Shareholder with: none, Grant / Research Support with: Maruho Co., Ltd 500,000 yen, Torii Pharmaceutical Co., Ltd 300,000 yen, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: none, S. Nakayamada Shareholder with: none, Grant / Research Support with: S. Nakayamada has received research grants from Mitsubishi-Tanabe, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: S Nakayamada has received consulting fees, lecture fees, and/or honoraria from Bristol-Myers, AstraZeneca, Pfizer, GlaxoSmithKline, AbbVie, Astellas, Asahi-kasei, Sanofi, Chugai, Eisai, Gilead Sciences, Boehringer Ingelheim., T. Nozawa Shareholder with: none, Grant / Research Support with: Chugai Pharma, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: none, T. Ohya Shareholder with: none, Grant / Research Support with: Chugai Pharma, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: none, N. Okamoto Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: N.O. has has received consulting fees from Daiichi Sankyo Company Limited; Eli Lilly Japan K.K.; and Swedish Orphan Biovitrum AB, Speaker Bureau with: N.O. has received honoraria or lecture fees from AbbVie Inc.; Amgen Inc.; Asahi Kasei Pharma Corporation; Astellas Pharma Inc.; AstraZeneca PLC; AYUMI Pharmaceutical Co., Ltd.; Bristol Myers Squibb; Chugai Pharmaceutical Co., Ltd.; Eisai Co., Ltd.; Eli Lilly Japan K.K.; GlaxoSmithKline PLC; Mitsubishi Tanabe Pharma Corporation; Novartis Pharma K.K.; Pfizer Inc.; and Teijin Pharma Limited; ., K. Sato Shareholder with: none, Grant / Research Support with: Chugai Pharmaceutical Co., Ltd, Four times, average 1,800,000 yen, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: Chugai Pharmaceutical Co., Ltd, One time, 100,000 yen, Y. Sugita Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: none, S. Takei Shareholder with: none, Grant / Research Support with: Chugai Pharcaceutical Co.Ltd., Eisai Co.Ltd., Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: Glaxo Smith Klein Pharmaceuticals Ltd, Novartis Pharma K.K., AbbVie, Mitsubishi Tanabe Pharma Corporation, Ayumimi Pharmaceutical Co, Bristol-Myers Squibb, Eli-Lilly,K.K., Asahi Kasei Medical Co.,, Sanofi, K.K. , S. Tanaka Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: none, Y. Tanaka Shareholder with: none, Grant / Research Support with: Y. Tanaka has received research grants from Asahi-Kasei, Abbvie, Chugai, Eisai, Takeda, Daiichi-Sankyo, Behringer-Ingelheim., Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: Y. Tanaka has received speaking fees and/or honoraria from Behringer-Ingelheim, Eli Lilly, Abbvie, Gilead, AstraZeneca, Bristol-Myers, Chugai, Daiichi-Sankyo, Eisai, Pfizer, Mitsubishi-Tanabe, GlaxoSmithKline, M. Tomiita Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: none, H. Umebayashi Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: Novaritis Pharma, Y. Yamasaki Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: none, N. Nishimoto Shareholder with: none, Grant / Research Support with: I have received financial grants from Chugai Pharmaceutical Co. Ltd.,the product company of tocilizumab., Consultant with: I have been work as a paid consultant for Chugai Pharmaceutical Co. Ltd. ,the product company of tocilizumab., Employee with: none, Paid Instructor with: I have been a paid instructor for Chugai Pharmaceutical Co. Ltd. ,the product company of tocilizumab., Speaker Bureau with: I have been paid as a speaker for Chugai Pharmaceutical Co. Ltd. ,the product company of tocilizumab., S. Yokota Shareholder with: none, Grant / Research Support with: none, Consultant with: none, Employee with: none, Paid Instructor with: none, Speaker Bureau with: none

Reference

1.

Yokota S, et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomized, double-blind, placebo-controlled, withdrawal phase III trial. Lancet. 2008 Mar 22;371(9617):998-1006.