Chen Yuanyuan, Linaburg Taylor, Wang Sarah, Merchant Gibran, Pradeep Tejus, Augello Patrick Anthony, Ying Gui-Shuang, Briceño César A, Tamhankar Madhura A
Scheie Eye Institute (YC, TL, SW, TP, PAA, G-sY, CAB, MAT), University of Pennsylvania, Philadelphia, Pennsylvania; Divisions of Neuro-ophthalmology (MAT), Oculoplastics (CAB), and Biostatistics (PAA, G-sY), Kansas Health Science Center, Kansas College of Osteopathic Medicine; and Kansas Health Science Center (GM), Kansas College of Osteopathic Medicine, Kansas, Missouri.
J Neuroophthalmol. 2025 Jan 9. doi: 10.1097/WNO.0000000000002280.
To characterize the retreatment course of patients with thyroid eye disease (TED), who had reactivation after initial therapy with teprotumumab.
This was a single-center longitudinal cohort study of patients who received an initial course of teprotumumab for active TED and were followed for at least 6 months. Reactivation was defined as the increase of proptosis of 2 mm or more or an increase in Clinical Activity Score (CAS) of two points or more, as adapted from the Optic-X study. Data collection included patient age, sex, smoking status, history of thyroidectomy or radioactive iodine, proptosis measurements, clinical activity score (CAS) before initial infusion of teprotumumab, time interval to reactivation, diplopia assessment by the Bahn-Gorman scale, CAS at the time of reactivation, and CAS and proptosis measurements after completion of retreatment and retreatment modalities, including clinical monitoring, corticosteroids, teprotumumab, and/or surgery. Among the reactivated cohort, the treatment response of patients who received a second course of teprotumumab was compared with patients who were treated with intravenous (IV) steroids.
Twenty-six percent (11/42) of patients experienced reactivation of TED with an average time to reactivation of 9 (SD:5) months (range: 2-20 months), average CAS at reactivation of 4 (SD:1) (range: 3-7), and average increase in proptosis of 3 (SD:1) mm (range: 2-6 mm). Of the 11 patients who reactivated, 4 received a second course of teprotumumab, while 6 received IV steroids. One patient elected to monitor. The patients who received a second course of teprotumumab had a mean (SD) posttreatment CAS score of 0 reduction in proptosis of 4 (2) mm (range: 3-6). The patients who received IV steroids had a mean (SD) posttreatment CAS of 2 (1) (range: 1-4) and a reduction in proptosis of 0 (1) mm (range: [-1] to [2]). Univariate analyses to look at predictors of reactivation found no correlation between factors such as age, sex, duration of TED, smoking status, presence of diplopia, previous treatment with radioactive iodine, history of periorbital surgery, and/or thyroidectomy after initial completion of teprotumumab between the 2 cohorts. We found a significant correlation between the CAS scores before initial treatment (P = 0.036) and thyroid hormone dysregulation (P = 0.006) in those who experienced reactivation.
Patients with TED may experience reactivation of the disease after initial therapy with teprotumumab. Reactivated disease responds to repeat therapy with teprotumumab with higher previous CAS and thyroid hormonal dysregulation being the variables that were significantly associated with reactivation. These data underscore the importance of long-term monitoring and exploring underlying triggers for disease reactivation. Understanding these factors could help predict which patients may require retreatment or chronic dosing with teprotumumab. Further studies are essential to advance our understanding of the immunomodulatory effects of teprotumumab, duration of its therapeutic benefit, and potential retreatment strategies to improve long-term patient outcomes.
为了描述甲状腺眼病（TED）患者在接受替普罗单抗初始治疗后病情复发的再治疗过程。
这是一项单中心纵向队列研究，研究对象为接受替普罗单抗初始疗程治疗的活动性TED患者，并随访至少6个月。复发定义为眼球突出增加2毫米或更多，或临床活动评分（CAS）增加2分或更多，这是根据Optic-X研究改编的。数据收集包括患者年龄、性别、吸烟状况、甲状腺切除术或放射性碘治疗史、眼球突出测量值、替普罗单抗初始输注前的临床活动评分（CAS）、复发时间间隔、通过Bahn-Gorman量表进行的复视评估、复发时的CAS以及再治疗完成后的CAS和眼球突出测量值，以及再治疗方式，包括临床监测、皮质类固醇、替普罗单抗和/或手术。在复发队列中，将接受第二疗程替普罗单抗治疗的患者的治疗反应与接受静脉注射（IV）类固醇治疗的患者进行比较。
26%（11/42）的患者经历了TED复发，平均复发时间为9（标准差：5）个月（范围：2 - 20个月），复发时平均CAS为4（标准差：1）（范围：3 - 7），眼球突出平均增加3（标准差：1）毫米（范围：2 - 6毫米）。在11例复发患者中，4例接受了第二疗程的替普罗单抗，6例接受了IV类固醇治疗。1例患者选择观察。接受第二疗程替普罗单抗治疗的患者治疗后CAS评分平均（标准差）降低0，眼球突出减少4（2）毫米（范围：3 - 6）。接受IV类固醇治疗的患者治疗后平均（标准差）CAS为2（1）（范围：1 - 4），眼球突出减少0（1）毫米（范围：[-1]至[2]）。单因素分析寻找复发的预测因素，发现两个队列中年龄、性别、TED病程、吸烟状况、复视的存在、既往放射性碘治疗、眶周手术史和/或替普罗单抗初始治疗完成后的甲状腺切除术等因素之间无相关性。我们发现复发患者初始治疗前的CAS评分（P = 0.036）与甲状腺激素失调（P = 0.006）之间存在显著相关性。
TED患者在接受替普罗单抗初始治疗后可能会出现疾病复发。复发的疾病对替普罗单抗重复治疗有反应，先前较高的CAS和甲状腺激素失调是与复发显著相关的变量。这些数据强调了长期监测和探索疾病复发潜在触发因素的重要性。了解这些因素有助于预测哪些患者可能需要再治疗或长期服用替普罗单抗。进一步的研究对于增进我们对替普罗单抗免疫调节作用、其治疗益处的持续时间以及改善患者长期预后的潜在再治疗策略的理解至关重要。
