XP-8121每周一次皮下注射左甲状腺素治疗成人甲减的2期研究
这项2期、多中心、非随机、开放标签、单臂、自身对照研究评估了XP-8121（皮下注射左甲状腺素钠）在46例成人甲减患者中的安全性、耐受性及口服转皮下的剂量转换系数。结果显示最终剂量转换系数点估计为4.02至4.24，支持约4倍于每日口服剂量的转换；完成研究者中TSH正常化率79.5%，fT4正常化率100%，最常见不良事件为疲劳和注射部位疼痛。
要点
- 口服左甲状腺素转换为XP-8121皮下注射的剂量转换系数约为每日口服剂量的4倍。
- 完成研究且剂量稳定者中，TSH正常化率79.5%，fT4正常化率100%。
- 最常见治疗中出现的不良事件为疲劳（21.7%）和注射部位疼痛（10.9%）。
核心结论
- 每周一次XP-8121皮下注射总体耐受性良好，并支持剂量转换系数为每日口服左甲状腺素剂量的4倍。
研究设计与样本
- 2期、多中心、非随机、开放标签、单臂、自身对照研究（NCT05823012），纳入46例成人甲减患者。
主要发现
- 最终剂量转换系数点估计范围为4.02（90%CI 3.79-4.27）至4.24（90%CI 4.06-4.42）。
- 完成研究且剂量稳定6周者中，TSH正常化率79.5%，fT4正常化率100%。
- 30例（65.2%）接受至少一剂XP-8121皮下注射的参与者报告78例治疗中出现的不良事件，最常见为疲劳（21.7%）和注射部位疼痛（10.9%）。
- 多数完成研究者报告对每周一次XP-8121皮下注射的满意度、便利性和感知有效性更高，并偏好该方案优于每日口服左甲状腺素。
临床怎么用
- 对于需要替代每日口服左甲状腺素的患者，可考虑每周一次XP-8121皮下注射，起始剂量约为目标剂量的50%，每2周根据fT4谷浓度滴定。
局限性
- 研究为非随机、开放标签、单臂、自身对照设计，样本量46例，完成者39例。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
BACKGROUND: The standard of care for hypothyroidism treatment worldwide is daily oral levothyroxine (LT4) sodium. Limitations associated with daily oral administration highlight the need for alternative formulations to address challenges in maintaining euthyroidism. XP-8121 (LT4 sodium for subcutaneous [SC] administration) is a ready-to-use, liquid formulation of LT4 intended for once-weekly administration, offering an alternative hormone replacement approach by bypassing the gastrointestinal tract. This study assessed the safety, tolerability, and target dose conversion factor from oral LT4 to XP-8121 SC in adult participants. PARTICIPANTS AND METHODS: This Phase 2, multicenter, nonrandomized, open-label, single-arm, self-controlled study (NCT05823012) evaluated XP-8121 SC in 46 adults with hypothyroidism receiving a consistent dose of oral LT4 for at least 3 months prior to screening, with documented normal thyrotropin (TSH) levels at least 3 months prior to screening and normal free thyroxine (fT4) at screening. The weekly XP-8121 SC dose was initiated at 50% of the target dose and titrated every 2 weeks for up to 8 weeks based on individual response using fT4 trough concentrations. Following titration, participants continued the established dose during a 4-week maintenance period. RESULTS: Of the 46 participants enrolled, 39 completed the study. The majority were female (37; 80.4%) and identified as White (44; 95.7%). The final dose conversion factor point estimate ranged from 4.02 (90% confidence interval [CI]: 3.79-4.27) to 4.24 (90% CI: 4.06-4.42), supporting a conversion factor of approximately four times the daily oral LT4 dose when transitioning to XP-8121 SC. Although participants were initially underdosed during titration, TSH normalization was observed in 79.5% and fT4 normalization in 100% among those who completed the study on a consistent dose (unchanged for 6 weeks) at the end of maintenance. Overall, 78 treatment-emergent adverse events (TEAEs) were reported in 30 participants (65.2%) who received at least one dose of XP-8121 SC; fatigue (21.7%) and injection-site pain (10.9%) were the most common TEAEs. A majority of participants who completed the study reported higher satisfaction, convenience, and perceived effectiveness with once-weekly XP-8121 SC and expressed preference over daily oral LT4. CONCLUSIONS: Once-weekly XP-8121 SC was generally well-tolerated in all treated participants and supported a dose conversion factor of four times the daily oral LT4 dose.
引用
- Conoscenti V, Huang R, Rudisill D, et al. A Phase 2 Study of XP-8121: Once-Weekly Subcutaneous Levothyroxine Sodium for the Treatment of Hypothyroidism in Adults. Thyroid. 2026. PMID: 42236452. doi:10.1177/10507256261454211
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。