Yuan Pan1, Yu-Xi Chen1, Jian Zhang1, Miao-Li Lin1,2, Guang-Ming Liu1,3, Xue-Liang Xu4,5,6,7, Xian-Qun Fan8, Yong Zhong9, Qing Li10, Si-Ming Ai1, Wen Xu11, Jia Tan4,6,7, Hui-Fang Zhou8, Dong-Dong Xu9, Hui-Ying Zhang10, Bei Xu4,6,7, Sha Wang4,6,7, Jun-Jie Ma4,6,7,12, Shuo Zhang8, Lin-Yang Gan9, Jian-Tao Cui9,13, Li Li10, Yan-Yan Xie1, Xinxing Guo14,15, Nathan Pan-Doh14, Zhuo-Ting Zhu1, Yao Lu1, Yu-Xun Shi1, Yi-Wen Xia1, Zuo-Yi Li1, Dan Liang1. 1. Department of Ocular Immunology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China. 2. C-MER Dennis Lam Eye Hospital, Shenzhen, China. 3. Department of Ophthalmology, The Third Affiliated Hospital of Soochow University, Changzhou, China. 4. Eye Center of Xiangya Hospital, Central South University, Changsha, China. 5. Department of Ophthalmology, Xiangya Changde Hospital, Changde, China. 6. Hunan Key Laboratory of Ophthalmology, Changsha, China. 7. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. 8. Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 9. Department of Ophthalmology, Peking Union Medical College Hospital, Beijing, China. 10. Department of Ophthalmology, Fujian Provincial Hospital, Fuzhou, China. 11. Department of Endocrinology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 12. Department of Ophthalmology, Huzhou Central Hospital, Huzhou, China. 13. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China. 14. Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland. 15. Dana Center of Preventive Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract
Importance: Mild thyroid-associated ophthalmopathy (TAO) negatively impacts quality of life, yet no clinical guidelines for its treatment are available. Existing evidence supports the use of doxycycline in treating mild TAO. Objective: To evaluate the short-term (12 weeks) efficacy of doxycycline in treating mild TAO. Design, Setting, and Participants: In this placebo-controlled multicenter randomized double-masked trial, 148 patients were assessed for eligibility. After exclusions (patients who were pregnant or lactating, had an allergy to tetracyclines, or had uncontrolled systematic diseases), 100 patients with mild TAO (orbital soft tissue affected mildly) at 5 centers in China were enrolled from July 2013 to December 2019 and monitored for 12 weeks. Interventions: Participants were randomly assigned 1:1 to receive doxycycline (50 mg) or placebo once daily for 12 weeks. Main Outcomes and Measures: The primary outcome was the rate of improvement at 12 weeks compared with baseline assessed by a composite indicator of eyelid aperture (reduction ≥2 mm), proptosis (reduction ≥2 mm), ocular motility (increase ≥8°), and Graves ophthalmopathy-specific quality-of-life (GO-QOL) scale score (increase ≥6 points). Adverse events were recorded. Results: A total of 50 participants were assigned to doxycycline and 50 to placebo. The mean (SD) age was 36.7 (9.1) years; 75 participants (75.0%) were female and 100 (100.0%) were Asian. Medication compliance was checked during participant interviews and by counting excess tablets. At week 12, the improvement rate was 38.0% (19 of 50) in the doxycycline group and 16.0% (8 of 50) in the placebo group (difference, 22.0%; 95% CI, 5.0-39.0; P = .01) in the intention-to-treat population. The per-protocol sensitivity analysis showed similar results (39.6% [19 of 48] vs 16.0% [8 of 50]; difference, 23.6%; 95% CI, 6.4-40.8; P = .009). No adverse events other than 1 case of mild gastric acid regurgitation was recorded in either group. Conclusions and Relevance: The results of this study indicate that oral doxycycline, 50 mg daily, resulted in greater improvement of TAO-related symptoms at 12 weeks compared with placebo in patients with mild TAO. These findings support the consideration of doxycycline for mild TAO but should be tempered by recognizing the relatively short follow-up and the size of the cohort. Trial Registration: ClinicalTrials.gov Identifier: NCT02203682.
Importance: Mild thyroid-associated ophthalmopathy (TAO) negatively impacts quality of life, yet no clinical guidelines for its treatment are available. Existing evidence supports the use of doxycycline in treating mild TAO. Objective: To evaluate the short-term (12 weeks) efficacy of doxycycline in treating mild TAO. Design, Setting, and Participants: In this placebo-controlled multicenter randomized double-masked trial, 148 patients were assessed for eligibility. After exclusions (patients who were pregnant or lactating, had an allergy to tetracyclines, or had uncontrolled systematic diseases), 100 patients with mild TAO (orbital soft tissue affected mildly) at 5 centers in China were enrolled from July 2013 to December 2019 and monitored for 12 weeks. Interventions: Participants were randomly assigned 1:1 to receive doxycycline (50 mg) or placebo once daily for 12 weeks. Main Outcomes and Measures: The primary outcome was the rate of improvement at 12 weeks compared with baseline assessed by a composite indicator of eyelid aperture (reduction ≥2 mm), proptosis (reduction ≥2 mm), ocular motility (increase ≥8°), and Graves ophthalmopathy-specific quality-of-life (GO-QOL) scale score (increase ≥6 points). Adverse events were recorded. Results: A total of 50 participants were assigned to doxycycline and 50 to placebo. The mean (SD) age was 36.7 (9.1) years; 75 participants (75.0%) were female and 100 (100.0%) were Asian. Medication compliance was checked during participant interviews and by counting excess tablets. At week 12, the improvement rate was 38.0% (19 of 50) in the doxycycline group and 16.0% (8 of 50) in the placebo group (difference, 22.0%; 95% CI, 5.0-39.0; P = .01) in the intention-to-treat population. The per-protocol sensitivity analysis showed similar results (39.6% [19 of 48] vs 16.0% [8 of 50]; difference, 23.6%; 95% CI, 6.4-40.8; P = .009). No adverse events other than 1 case of mild gastric acid regurgitation was recorded in either group. Conclusions and Relevance: The results of this study indicate that oral doxycycline, 50 mg daily, resulted in greater improvement of TAO-related symptoms at 12 weeks compared with placebo in patients with mild TAO. These findings support the consideration of doxycycline for mild TAO but should be tempered by recognizing the relatively short follow-up and the size of the cohort. Trial Registration: ClinicalTrials.gov Identifier: NCT02203682.
Authors: Claudio Marcocci; George J Kahaly; Gerasimos E Krassas; Luigi Bartalena; Mark Prummel; Matthias Stahl; Maria Antonietta Altea; Marco Nardi; Susanne Pitz; Kostas Boboridis; Paolo Sivelli; George von Arx; Maarten P Mourits; Lelio Baldeschi; Walter Bencivelli; Wilmar Wiersinga Journal: N Engl J Med Date: 2011-05-19 Impact factor: 91.245