The Jules Stein Eye Institute University of California, Los Angeles, Los Angeles, USA.
Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Eye (Lond). 2022 Jul;36(7):1403-1408. doi: 10.1038/s41433-021-01539-5. Epub 2021 Jun 28.
In recent trials, 50% of patients treated with teprotumumab for thyroid eye disease had significant improvements in proptosis at 6 weeks. However, a small subgroup of patients did not have a significant response by week 12. We examine the outcomes at week 24 in patients from both trials who had little or no proptosis response at week 12.
In this post hoc analysis, data from teprotumumab-treated patients in the placebo-controlled randomized phases 2 and 3 trials were reviewed.
Patients treated with teprotumumab or placebo with a ≤2 mm reduction from baseline in proptosis at week 12 and completed assessments at both the weeks 12 and 24 visits were included. The main outcome measures were a change in proptosis, clinical activity score (CAS) and diplopia in response to teprotumumab therapy at baseline and weeks 6, 12, 18, and 24.
From the phases 2 and 3 studies, 24 patients from the treated and placebo groups were included for analysis (48 total). In the teprotumumab group, of the 24 who had no improvement in proptosis (≥2 mm from baseline) at 12 weeks, 15 (63%) demonstrated a clinically significant improvement at week 24. No patients from the 24 placebo patients had a clinically significant improvement in proptosis at 12 weeks, and 24 weeks. At week 12, 22 patients (92%) in the teprotumumab group had a significant reduction in the CAS (≥2 points) and at 24 weeks all patients achieved this reduction. At week 12, 11 (46%) patients from the placebo group had a significant improvement, while 10 (42%) had a significant improvement at 24 weeks. 22 of the 24 patients (92%) in the teprotumumab group had a diplopia grade > 0 at baseline. At week 12, 12 of the 22 (55%) had improvement in diplopia ≥ 1 grade. By week 24, 16 patients (73%) had an improvement in diplopia ≥ 1 grade. In the placebo group, 15 (63%) had significant diplopia. At week 12, 3 (20%) from this group had improvement in diplopia ≥ 1 grade, while at 24 weeks this number rose to 4 (27%).
There is variability in the time taken to manifest a clinically significant response to teprotumumab, some patients my need a longer time to respond.
在最近的试验中，50%接受替普妥单抗治疗甲状腺眼病的患者在 6 周时眼球突出有显著改善。然而，一小部分患者在 12 周时没有明显的反应。我们检查了这两项试验中在第 12 周眼球突出反应小或无反应的患者在第 24 周的结果。
在这项事后分析中，回顾了安慰剂对照随机 2 期和 3 期试验中接受替普妥单抗治疗的患者的数据。
纳入了在第 12 周时眼球突出从基线下降了≤2 毫米，并且在第 12 周和第 24 周访视时完成了评估的接受替普妥单抗或安慰剂治疗的患者。主要观察指标是在基线和第 6、12、18 和 24 周时对替普妥单抗治疗的眼球突出、临床活动评分（CAS）和复视的变化。
从 2 期和 3 期研究中，纳入了治疗组和安慰剂组的 24 名患者进行分析（共 48 名）。在替普妥单抗组中，在第 12 周时眼球突出没有改善（较基线增加≥2 毫米）的 24 名患者中，有 15 名（63%）在第 24 周时出现了临床显著改善。在第 12 周时，24 名安慰剂患者中没有一名患者的眼球突出有临床显著改善，在第 24 周时也没有。在第 12 周时，替普妥单抗组的 22 名患者（92%）的 CAS 显著降低（≥2 分），而在第 24 周时所有患者均达到了这一降低。在第 12 周时，安慰剂组有 11 名（46%）患者的改善显著，而在第 24 周时，有 10 名（42%）患者的改善显著。替普妥单抗组的 24 名患者中有 22 名（92%）在基线时有≥0 级的复视。在第 12 周时，22 名中的 12 名（55%）患者的复视改善了≥1 级。到第 24 周时，16 名患者（73%）的复视改善了≥1 级。在安慰剂组中，有 15 名（63%）患者有明显的复视。在第 12 周时，该组中有 3 名（20%）患者的复视改善了≥1 级，而在第 24 周时这一数字上升到了 4 名（27%）。
对替普妥单抗有临床显著反应的时间存在差异，有些患者可能需要更长的时间才能作出反应。
