Bertolotto Antonio, Arroyo Rafael, Celius Elisabeth G, Comi Giancarlo, Havrdova Eva Kubala, Honeycutt William David, Hunter Samuel F, Izquierdo Guillermo, Kornek Barbara, Miller Tamara, Mitsikostas Dimos D, Singer Barry A, Ziemssen Tjalf, Chung Luke, Daizadeh Nadia, Afsar Salman, Hashemi Lobat, Senior Peter
SCDO Neurologia-CRESM (Centro Riferimento Regionale Sclerosi Multipla), University Hospital San Luigi Gonzaga, Orbassano, Turin, Italy.
Hospital Universitario Quirónsalud Madrid, Madrid, Spain.
Neurol Ther. 2020 Dec;9(2):443-457. doi: 10.1007/s40120-020-00191-7. Epub 2020 May 14.
In clinical trials of alemtuzumab, autoimmune thyroid adverse events (AEs) were frequent. Here, we assess the impact of thyroid AEs on health-related quality of life (HRQL) in alemtuzumab-treated patients with relapsing-remitting multiple sclerosis (RRMS).
In phase 3 CARE-MS I (NCT00530348) and II (NCT00548405) trials, patients with RRMS were administered alemtuzumab 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. Patients could participate in an extension study (NCT00930553) through year 6. HRQL was assessed at baseline and annually using the Functional Assessment of Multiple Sclerosis (FAMS), EuroQoL-5 Dimension Visual Analog Scale (EQ-5D VAS), and 36-Item Short-Form Survey (SF-36) questionnaires. Outcomes were analyzed in patients with or without thyroid AEs (nonserious or serious). A subset of patients with thyroid AEs was analyzed to assess HRQL before and during the onset of thyroid AEs.
A total of 811 CARE-MS patients were treated with alemtuzumab. Of these, 342 (42%) patients experienced thyroid AEs over 6 years; serious thyroid AEs occurred in 44 (5%) patients. At year 6, HRQL outcomes generally remained slightly improved or similar to core study baseline in alemtuzumab-treated patients with or without thyroid AEs: FAMS (least-squares mean change from baseline without thyroid AEs, 0.7; with nonserious thyroid AEs, 5.1; with serious thyroid AEs, - 5.3), EQ-5D VAS (2.0; 3.0; - 6.8), SF-36 mental component summary (MCS [0.6; 1.6; - 2.8]), SF-36 physical component summary (PCS [0.8; 1.0; 1.1]). Over 6 years, 63-82% of patients in each group had improved/stable SF-36 MCS and PCS scores. Among patients with thyroid AE onset in year 3 (peak incidence), there were minimal differences between HRQL outcomes before onset (year 2) and after onset (year 3).
Autoimmune thyroid AEs (serious and nonserious) had minimal impact on HRQL in alemtuzumab-treated patients. These data may aid therapeutic decisions in patients with relapsing MS.
在阿仑单抗的临床试验中，自身免疫性甲状腺不良事件（AE）很常见。在此，我们评估甲状腺AE对接受阿仑单抗治疗的复发缓解型多发性硬化症（RRMS）患者健康相关生活质量（HRQL）的影响。
在3期CARE-MS I（NCT00530348）和II（NCT00548405）试验中，RRMS患者在基线时连续5天每天接受12 mg阿仑单抗治疗，12个月后连续3天每天接受12 mg阿仑单抗治疗。患者可参加为期6年的扩展研究（NCT00930553）。在基线时和每年使用多发性硬化症功能评估（FAMS）、欧洲五维视觉模拟量表（EQ-5D VAS）和36项简短调查（SF-36）问卷评估HRQL。对有或无甲状腺AE（非严重或严重）的患者的结果进行分析。对一部分甲状腺AE患者进行分析，以评估甲状腺AE发作前和发作期间的HRQL。
共有811例CARE-MS患者接受了阿仑单抗治疗。其中，342例（42%）患者在6年内出现甲状腺AE；44例（5%）患者出现严重甲状腺AE。在第6年，无论有无甲状腺AE，接受阿仑单抗治疗的患者的HRQL结果总体上仍略有改善或与核心研究基线相似：FAMS（无甲状腺AE组从基线的最小二乘平均变化为0.7；非严重甲状腺AE组为5.1；严重甲状腺AE组为-5.3），EQ-5D VAS（2.0；3.0；-6.8），SF-36精神成分总结（MCS[0.6；1.6；-2.8]），SF-36身体成分总结（PCS[0.8；1.0；1.1]）。在6年期间，每组63%-82%的患者的SF-36 MCS和PCS评分有所改善/保持稳定。在第3年（发病高峰）出现甲状腺AE的患者中，发病前（第2年）和发病后（第3年）的HRQL结果差异最小。
自身免疫性甲状腺AE（严重和非严重）对接受阿仑单抗治疗的患者的HRQL影响最小。这些数据可能有助于复发型MS患者的治疗决策。
