Kavakli K, Demartis F, Karimi M, Eshghi P, Neme D, Chambost H, Sommer L, Zak M, Benson G
Department of Hematology, Ege University Children's Hospital, Izmir, Turkey.
Careggi Agenzia per l'Emofilia, A.O.U.C. Azienda Ospedaliero-Universitaria, Firenze, Italy.
Haemophilia. 2017 Jul;23(4):575-582. doi: 10.1111/hae.13227. Epub 2017 Apr 24.
A room temperature stable formulation of recombinant activated factor VII (NovoSeven ), allowing convenient storage and therefore improved treatment access, has been developed. Bioequivalence to the previous NovoSeven was demonstrated in healthy humans, leading to European approval (2008). Although no confirmed cases of neutralising antibodies to rFVIIa in patients with haemophilia A or B have been observed with the original formulation, changes in formulation or storage condition may alter immunogenicity.
SMART-7™ was designed to investigate the safety of NovoSeven in a real-world setting in patients with haemophilia A or B with inhibitors.
Study medication was not provided by the sponsor, and treatment was at the discretion of the treating physician, in accordance with the local label. Patient baseline information was collected at enrolment. Information on safety, drug exposure and bleeding episodes was collected and FVII antibody screening was encouraged at baseline and performed at the investigator's discretion.
Fifty-one patients were enrolled and 31 completed the study. Forty-one adverse events (AEs) were reported in 23 patients; 25 AEs in 14 patients were serious. No thromboembolic events were observed. Although four cases of reduced therapeutic response were reported, FVII antibody screening was negative. Forty-eight patients experienced 618 bleeding episodes and 93.4% of 609 evaluated bleeds were stopped by treatment. Of the 538 bleeding episodes treated with NovoSeven monotherapy, 94.2% stopped by end of treatment.
Data collected during the SMART-7™ study revealed no treatment-related safety issues and no FVII-binding antibodies for patients treated with NovoSeven under real-world conditions.
已研发出一种重组活化因子VII（诺其）在室温下稳定的制剂，便于储存，从而改善了治疗的可及性。在健康人体中证明了其与之前的诺其具有生物等效性，并于2008年获得欧洲批准。尽管最初的制剂在A型或B型血友病患者中未观察到针对重组凝血因子VIIa的中和抗体确诊病例，但制剂或储存条件的改变可能会改变免疫原性。
SMART-7™旨在研究诺其在现实环境中对伴有抑制剂的A型或B型血友病患者的安全性。
研究药物并非由申办方提供，治疗由主治医生根据当地标签自行决定。在入组时收集患者基线信息。收集有关安全性、药物暴露和出血事件的信息，并在基线时鼓励进行FVII抗体筛查，由研究者自行决定是否进行检测。
51名患者入组，31名完成研究。23名患者报告了41例不良事件（AE）；14名患者中的25例AE为严重不良事件。未观察到血栓栓塞事件。尽管报告了4例治疗反应降低的病例，但FVII抗体筛查为阴性。48名患者发生了618次出血事件，在609次评估的出血事件中，93.4%经治疗后出血停止。在用诺其单药治疗的538次出血事件中，94.2%在治疗结束时出血停止。
SMART-7™研究期间收集的数据显示，在现实条件下接受诺其治疗的患者中，未发现与治疗相关的安全问题，也未发现FVII结合抗体。
