Supplementary Material for: Glucosamine use reduces the risk of first-ever optic neuritis: A nationwide 16-year longitudinal analysis

Introduction: Evidence of neuroprotective effects of glucosamine on Asian optic neuritis (ON) patients remains sparse. We aimed to examine the longitudinal association between glucosamine use and the incidence of first-ever ON to identify the factors contributing to reducing ON risk in older Asian populations.

Methods: This nationwide cohort study from 2000 to 2015 evaluated 24,155 individuals. The International Classification of Diseases-9-Clinical Modification code 377 determined newly diagnosed ON. Outcomes include the annual trend of first-ever ON incidence, crude/adjusted hazard ratios (HRs) of incident ON stratified by sociodemographic characteristics and comorbidities.

Results: Glucosamine exposure has been significantly associated with reduced ON incidence (Log-rank p < 0.001) since the fifth year of clinical surveillance. The overall adjusted HR of ON among glucosamine users was 0.718 (CI = 0.524–0.901, p = 0.001), and in the glucosamine-exposed group, disease onset was approximately 129 days later than in non-users (6.83 ± 4.27 vs. 6.47 ± 4.01 years to ON, p < 0.001). Moreover, glucosamine was associated with reduced ON risk in patients without diabetes mellitus, hypertension, tobacco use and chronic heart failure. While administering glucosamine, the risk was reduced by more than half among individuals aged between 45 and 64 years (aHR = 0.433, CI = 0.316–0.544, p < 0.001) and patients from medical centers (aHR = 0.453, CI = 0.330–0.568, p < 0.001).

Conclusion: Taiwanese glucosamine users have a decreased risk of developing ON. Our work provides a theoretical basis for expanding glucosamine indications in regions with minimal prevalence of ON.

引言：氨基葡萄糖（glucosamine）对亚洲视神经炎（optic neuritis, ON）患者的神经保护作用相关证据仍较为匮乏。本研究旨在探讨氨基葡萄糖使用与首次发作视神经炎发病率之间的纵向关联，以期明确可降低老年亚洲人群视神经炎发病风险的相关影响因素。
方法：本项2000年至2015年的全国性队列研究共纳入24155名研究对象。以国际疾病分类第9版临床修正版（International Classification of Diseases-9-Clinical Modification, ICD-9-CM）编码377作为新诊断视神经炎的判定标准。研究结局指标包括首次发作视神经炎发病率的年度变化趋势，以及按社会人口学特征和合并症分层的新发视神经炎粗风险比与校正风险比（hazard ratios, HRs）。
结果：自临床随访第5年起，氨基葡萄糖暴露与视神经炎发病率降低存在显著相关性（Log-rank检验，p < 0.001）。氨基葡萄糖使用者的视神经炎总体校正风险比为0.718（置信区间（confidence interval, CI）：0.524~0.901，p = 0.001）；且氨基葡萄糖暴露组患者的发病时间较非使用者延迟约129天（至视神经炎发作的时间分别为6.83±4.27年 vs 6.47±4.01年，p < 0.001）。此外，在无糖尿病、高血压、吸烟史及慢性心力衰竭的患者中，氨基葡萄糖使用与视神经炎发病风险降低相关。其中，45~64岁人群（校正风险比aHR=0.433，置信区间CI：0.316~0.544，p < 0.001）及医疗中心就诊患者（校正风险比aHR=0.453，置信区间CI：0.330~0.568，p < 0.001）的发病风险降低超过50%。
结论：台湾地区氨基葡萄糖使用者的视神经炎发病风险显著降低。本研究为在视神经炎患病率较低的地区拓展氨基葡萄糖的临床适应症提供了理论依据。