PDF(Pubmed)
Abstract：
Azathioprine (AZA) interferes with the activation of T and B lymphocytes, which are the main cells involved in the pathogenesis of Graves\' disease (GD). The aim of this study was to investigate the effectiveness of AZA as an adjuvant therapy to antithyroid drugs (ATDs) for moderate and severe GD. In addition, we conducted an incremental cost-effectiveness analysis of AZA to determine its cost-effectiveness.
We conducted a randomized, open-label, and parallel-group clinical trial. We randomized untreated hyperthyroid patients with severe GD into three groups. All patients received 45-mg carbimazole (CM) as the starting dose and propranolol 40-120 mg daily. The first group (AZA1) received an additional 1 mg/kg/day AZA, the second group (AZA2) received an additional 2 mg/kg/day AZA, and the third group (control group) received only CM and propranolol. We measured thyroid-stimulating hormone (TSH) and TSH-receptor antibody (TRAb) levels at baseline and every 3 months, while free triiodothyronine (FT3) and free thyroxine (FT4) levels were measured at the time of diagnosis, 1 month after initiation of therapy, and every 3 months thereafter until 2 years after remission. Thyroid volume (TV) was assessed by ultrasound at baseline and 1 year after remission.
A total of 270 patients were included in this trial. By the end of follow-up, there was higher remission rate in the AZA1 and AZA2 groups compared with controls (87.5% and 87.5% vs. 33.4%, p = 0.002). Throughout the course of follow-up, FT3, FT4, TSH, and TRAb were significantly different between the AZA groups and the control group, but there was no significant difference regarding TV. The decline in the concentrations of FT4, FT3, and TRAb was significantly faster in the AZA2 group than in the AZA1 group. The relapse rate during the 12-month follow-up was insignificantly higher in the control group than in either the AZA1 or AZA2 group (10, 4.4, and 4.4%, p = 0.05, respectively). The median relapse time was 18 months for the control group and 24 months for the AZA1 and AZA2 groups. The incremental cost-effectiveness ratio for the AZA group compared with the conventional group was 27,220.4 Egyptian pounds per remission reduction for patients using AZA as an adjuvant for ATDs.
AZA could be a novel, affordable, cost-effective, and safe drug offering hope for patients with GD to achieve early and long-lasting medical remission.
The trial is registered at the Pan African Clinical Trial Registry (Registration number: PACTR201912487382180).
We conducted a randomized, open-label, and parallel-group clinical trial. We randomized untreated hyperthyroid patients with severe GD into three groups. All patients received 45-mg carbimazole (CM) as the starting dose and propranolol 40-120 mg daily. The first group (AZA1) received an additional 1 mg/kg/day AZA, the second group (AZA2) received an additional 2 mg/kg/day AZA, and the third group (control group) received only CM and propranolol. We measured thyroid-stimulating hormone (TSH) and TSH-receptor antibody (TRAb) levels at baseline and every 3 months, while free triiodothyronine (FT3) and free thyroxine (FT4) levels were measured at the time of diagnosis, 1 month after initiation of therapy, and every 3 months thereafter until 2 years after remission. Thyroid volume (TV) was assessed by ultrasound at baseline and 1 year after remission.
A total of 270 patients were included in this trial. By the end of follow-up, there was higher remission rate in the AZA1 and AZA2 groups compared with controls (87.5% and 87.5% vs. 33.4%, p = 0.002). Throughout the course of follow-up, FT3, FT4, TSH, and TRAb were significantly different between the AZA groups and the control group, but there was no significant difference regarding TV. The decline in the concentrations of FT4, FT3, and TRAb was significantly faster in the AZA2 group than in the AZA1 group. The relapse rate during the 12-month follow-up was insignificantly higher in the control group than in either the AZA1 or AZA2 group (10, 4.4, and 4.4%, p = 0.05, respectively). The median relapse time was 18 months for the control group and 24 months for the AZA1 and AZA2 groups. The incremental cost-effectiveness ratio for the AZA group compared with the conventional group was 27,220.4 Egyptian pounds per remission reduction for patients using AZA as an adjuvant for ATDs.
AZA could be a novel, affordable, cost-effective, and safe drug offering hope for patients with GD to achieve early and long-lasting medical remission.
The trial is registered at the Pan African Clinical Trial Registry (Registration number: PACTR201912487382180).
摘要：
■硫唑嘌呤（AZA）干扰T和B淋巴细胞的激活，它们是参与Graves病(GD)发病的主要细胞。这项研究的目的是研究AZA作为中度和重度GD的抗甲状腺药物（ATDs）辅助治疗的有效性。此外,我们对AZA进行了增量成本效益分析,以确定其成本效益.
■我们进行了随机，开放标签，和平行组临床试验。我们将未经治疗的重度GD甲状腺功能亢进患者随机分为三组。所有患者均接受45mg卡比马唑（CM）作为起始剂量，每天接受普萘洛尔40-120mg。第一组（AZA1）额外接受1mg/kg/天的AZA，第二组（AZA2）额外接受2mg/kg/天的AZA，第三组（对照组）仅接受CM和普萘洛尔。我们在基线和每3个月测量促甲状腺激素（TSH）和TSH受体抗体（TRAb）水平，而在诊断时测量游离三碘甲状腺原氨酸（FT3）和游离甲状腺素（FT4）水平，治疗开始后1个月，此后每3个月，直到缓解后2年。在基线和缓解后1年通过超声评估甲状腺体积（TV）。
■本试验共纳入270例患者。在后续行动结束时，与对照组相比，AZA1和AZA2组的缓解率更高（87.5％和87.5％vs.33.4%,p=0.002)。在整个后续行动过程中，FT3,FT4,TSH,和TRAb在AZA组和对照组之间有显著差异，但是关于电视没有显着差异。AZA2组FT4、FT3、TRAb浓度下降速度明显快于AZA1组。在12个月随访期间，对照组的复发率明显高于AZA1或AZA2组（10、4.4和4.4％，分别为p=0.05)。对照组的中位复发时间为18个月，AZA1和AZA2组为24个月。对于使用AZA作为ATDs辅助治疗的患者，与常规组相比，AZA组的增量成本效益比为每缓解减少27,220.4埃及磅。
■AZA可能是一部小说，负担得起的,成本效益高,和安全的药物为GD患者提供了希望，以实现早期和长期的药物缓解。
■该试验已在泛非临床试验注册中心注册（注册编号：PACTR201912487382180）。
■我们进行了随机，开放标签，和平行组临床试验。我们将未经治疗的重度GD甲状腺功能亢进患者随机分为三组。所有患者均接受45mg卡比马唑（CM）作为起始剂量，每天接受普萘洛尔40-120mg。第一组（AZA1）额外接受1mg/kg/天的AZA，第二组（AZA2）额外接受2mg/kg/天的AZA，第三组（对照组）仅接受CM和普萘洛尔。我们在基线和每3个月测量促甲状腺激素（TSH）和TSH受体抗体（TRAb）水平，而在诊断时测量游离三碘甲状腺原氨酸（FT3）和游离甲状腺素（FT4）水平，治疗开始后1个月，此后每3个月，直到缓解后2年。在基线和缓解后1年通过超声评估甲状腺体积（TV）。
■本试验共纳入270例患者。在后续行动结束时，与对照组相比，AZA1和AZA2组的缓解率更高（87.5％和87.5％vs.33.4%,p=0.002)。在整个后续行动过程中，FT3,FT4,TSH,和TRAb在AZA组和对照组之间有显著差异，但是关于电视没有显着差异。AZA2组FT4、FT3、TRAb浓度下降速度明显快于AZA1组。在12个月随访期间，对照组的复发率明显高于AZA1或AZA2组（10、4.4和4.4％，分别为p=0.05)。对照组的中位复发时间为18个月，AZA1和AZA2组为24个月。对于使用AZA作为ATDs辅助治疗的患者，与常规组相比，AZA组的增量成本效益比为每缓解减少27,220.4埃及磅。
■AZA可能是一部小说，负担得起的,成本效益高,和安全的药物为GD患者提供了希望，以实现早期和长期的药物缓解。
■该试验已在泛非临床试验注册中心注册（注册编号：PACTR201912487382180）。
