A randomised, double-masked, placebo-controlled trial evaluating the efficacy and safety of teprotumumab for active thyroid eye disease in Japanese patientsResearch in context
Summary: Background: Teprotumumab significantly improved proptosis and diplopia in patients with active, moderate-to-severe thyroid eye disease (TED) in previous North American and European studies. This is the first evaluation of efficacy and safety of teprotumumab for active, moderate-to-severe T...
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Elsevier
2025-02-01
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| Series: | The Lancet Regional Health. Western Pacific |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S266660652500001X |
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| author | Yuji Hiromatsu Eri Ishikawa Ai Kozaki Yasuhiro Takahashi Mika Tanabe Ken Hayashi Yukihiro Imagawa Kazutoyo Kaneda Masashi Mimura Xiaoxian Dai Tomoko Hayashida Takashi Akamizu |
| author_facet | Yuji Hiromatsu Eri Ishikawa Ai Kozaki Yasuhiro Takahashi Mika Tanabe Ken Hayashi Yukihiro Imagawa Kazutoyo Kaneda Masashi Mimura Xiaoxian Dai Tomoko Hayashida Takashi Akamizu |
| author_sort | Yuji Hiromatsu |
| collection | DOAJ |
| description | Summary: Background: Teprotumumab significantly improved proptosis and diplopia in patients with active, moderate-to-severe thyroid eye disease (TED) in previous North American and European studies. This is the first evaluation of efficacy and safety of teprotumumab for active, moderate-to-severe TED in Japanese patients. Methods: This randomised, double-masked, placebo-controlled trial was conducted in 16 centres in Japan. Main inclusion criteria were as follows: age 20–80 years; Graves’ disease, in a euthyroid or mild hypo/hyperthyroid state; clinical activity score (CAS) ≥3; moderate-to-severe TED; ≥3-mm increase in proptosis before TED onset and/or proptosis ≥18 mm at baseline; and TED duration ≤9 months. Patients were randomised (1:1, stratified by smoking status) to either teprotumumab or placebo. Patients received eight intravenous infusions, one every three weeks for 24 weeks. Patients, investigators, site personnel (except formulating pharmacists) were masked. Primary endpoint was proptosis responder rate (percentage of patients with ≥2-mm proptosis reduction from baseline) at week 24 in the intent-to-treat population. Adverse events were assessed in all patients. This trial was registered at Japan Registry for Clinical Trials (jRCT2031210453). Findings: Fifty-four patients were randomised (teprotumumab, 27; placebo, 27) between February and November 2022. All patients completed the randomised period, although one teprotumumab patient and two placebo patients missed ≥2 doses. At week 24, the proportion of patients with proptosis response was higher in the teprotumumab group (89%, 24/27) compared with the placebo group (11%, 3/27), 95% confidence interval, 61–95; P<0.0001. Study drug-related adverse events (AEs) occurred in 14 patients (52%) in the teprotumumab group and two patients (7%) in the placebo group; hyperglycaemia-related events were reported in six (22%) and one patient (4%), and hearing impairment in four (15%) and one (4%) patient, respectively. Study drug-related serious AEs and deaths were not reported. Interpretation: Teprotumumab significantly improved proptosis compared with placebo in Japanese patients with active TED. No study drug-related serious AEs were observed. Funding: Horizon Therapeutics plc (now Amgen). |
| format | Article |
| id | doaj-art-0759a148e65f4d5abc32cb7cef544d11 |
| institution | Kabale University |
| issn | 2666-6065 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | The Lancet Regional Health. Western Pacific |
| spelling | doaj-art-0759a148e65f4d5abc32cb7cef544d112025-01-20T04:17:57ZengElsevierThe Lancet Regional Health. Western Pacific2666-60652025-02-0155101464A randomised, double-masked, placebo-controlled trial evaluating the efficacy and safety of teprotumumab for active thyroid eye disease in Japanese patientsResearch in contextYuji Hiromatsu0Eri Ishikawa1Ai Kozaki2Yasuhiro Takahashi3Mika Tanabe4Ken Hayashi5Yukihiro Imagawa6Kazutoyo Kaneda7Masashi Mimura8Xiaoxian Dai9Tomoko Hayashida10Takashi Akamizu11Diabetes, Thyroid and Endocrine Center, Shin Koga Hospital, 120 Tenjin-cho, Kurume, Fukuoka 830-8577, Japan; Corresponding author.Kozawa Eye Hospital and Diabetes Center, 246-6 Yoshizawa-cho, Mito-shi, Ibaraki 310-0845, JapanOlympia Eye Hospital, 2-18-12 Jinguumae, Shibuya-ku, Tokyo 150-0001, JapanDepartment of Oculoplastic, Orbital & Lacrimal Surgery, Aichi Medical University Hospital, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, JapanDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanHayashi Eye Hospital, 4-23-35 Hakataekimae, Hakata-ku, Fukuoka 812-0011, JapanOculoplastic Surgery Center, Department of Ophthalmology, Osaka Kaisei Hospital, 1-6-10 Miyahara, Yodogawa-ku, Osaka 532-0003, JapanMiyazaki Chuo Eye Hospital, 3-6-21 Shimizu, Miyazaki-shi, Miyazaki 880-0021, JapanOculoplastic Surgery Center, Department of Ophthalmology, Osaka Kaisei Hospital, 1-6-10 Miyahara, Yodogawa-ku, Osaka 532-0003, JapanAmgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USAAmgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USAKuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe 650-0011, JapanSummary: Background: Teprotumumab significantly improved proptosis and diplopia in patients with active, moderate-to-severe thyroid eye disease (TED) in previous North American and European studies. This is the first evaluation of efficacy and safety of teprotumumab for active, moderate-to-severe TED in Japanese patients. Methods: This randomised, double-masked, placebo-controlled trial was conducted in 16 centres in Japan. Main inclusion criteria were as follows: age 20–80 years; Graves’ disease, in a euthyroid or mild hypo/hyperthyroid state; clinical activity score (CAS) ≥3; moderate-to-severe TED; ≥3-mm increase in proptosis before TED onset and/or proptosis ≥18 mm at baseline; and TED duration ≤9 months. Patients were randomised (1:1, stratified by smoking status) to either teprotumumab or placebo. Patients received eight intravenous infusions, one every three weeks for 24 weeks. Patients, investigators, site personnel (except formulating pharmacists) were masked. Primary endpoint was proptosis responder rate (percentage of patients with ≥2-mm proptosis reduction from baseline) at week 24 in the intent-to-treat population. Adverse events were assessed in all patients. This trial was registered at Japan Registry for Clinical Trials (jRCT2031210453). Findings: Fifty-four patients were randomised (teprotumumab, 27; placebo, 27) between February and November 2022. All patients completed the randomised period, although one teprotumumab patient and two placebo patients missed ≥2 doses. At week 24, the proportion of patients with proptosis response was higher in the teprotumumab group (89%, 24/27) compared with the placebo group (11%, 3/27), 95% confidence interval, 61–95; P<0.0001. Study drug-related adverse events (AEs) occurred in 14 patients (52%) in the teprotumumab group and two patients (7%) in the placebo group; hyperglycaemia-related events were reported in six (22%) and one patient (4%), and hearing impairment in four (15%) and one (4%) patient, respectively. Study drug-related serious AEs and deaths were not reported. Interpretation: Teprotumumab significantly improved proptosis compared with placebo in Japanese patients with active TED. No study drug-related serious AEs were observed. Funding: Horizon Therapeutics plc (now Amgen).http://www.sciencedirect.com/science/article/pii/S266660652500001XTeprotumumabProptosisClinical activity scoreThyroid eye diseaseRandomisedDouble-masked |
| spellingShingle | Yuji Hiromatsu Eri Ishikawa Ai Kozaki Yasuhiro Takahashi Mika Tanabe Ken Hayashi Yukihiro Imagawa Kazutoyo Kaneda Masashi Mimura Xiaoxian Dai Tomoko Hayashida Takashi Akamizu A randomised, double-masked, placebo-controlled trial evaluating the efficacy and safety of teprotumumab for active thyroid eye disease in Japanese patientsResearch in context The Lancet Regional Health. Western Pacific Teprotumumab Proptosis Clinical activity score Thyroid eye disease Randomised Double-masked |
| title | A randomised, double-masked, placebo-controlled trial evaluating the efficacy and safety of teprotumumab for active thyroid eye disease in Japanese patientsResearch in context |
| title_full | A randomised, double-masked, placebo-controlled trial evaluating the efficacy and safety of teprotumumab for active thyroid eye disease in Japanese patientsResearch in context |
| title_fullStr | A randomised, double-masked, placebo-controlled trial evaluating the efficacy and safety of teprotumumab for active thyroid eye disease in Japanese patientsResearch in context |
| title_full_unstemmed | A randomised, double-masked, placebo-controlled trial evaluating the efficacy and safety of teprotumumab for active thyroid eye disease in Japanese patientsResearch in context |
| title_short | A randomised, double-masked, placebo-controlled trial evaluating the efficacy and safety of teprotumumab for active thyroid eye disease in Japanese patientsResearch in context |
| title_sort | randomised double masked placebo controlled trial evaluating the efficacy and safety of teprotumumab for active thyroid eye disease in japanese patientsresearch in context |
| topic | Teprotumumab Proptosis Clinical activity score Thyroid eye disease Randomised Double-masked |
| url | http://www.sciencedirect.com/science/article/pii/S266660652500001X |
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