A post-marketing surveillance study on the safety and effectiveness of recombinant antithrombin gamma in patients with congenital antithrombin deficiency in Japan

TL;DR

This study evaluated the safety and effectiveness of a treatment for a rare blood clotting disorder in Japanese patients, finding it generally safe and effective, especially during pregnancy.

Contribution

The study provides real-world evidence on the safety and effectiveness of recombinant antithrombin gamma in Japanese patients with congenital antithrombin deficiency.

Findings

rhAT-gamma was judged effective in all patients, with increased antithrombin activity in most.

Among pregnant women, no thrombosis occurred before or after delivery, leading to safe childbirth outcomes.

Adverse events were observed in 31.8% of patients, but no deaths occurred.

Abstract

Congenital antithrombin deficiency (CAD) is a serious inherited thrombophilia, classified as a rare disease. According to a study measuring antithrombin (AT) activity in the general Japanese population, approximately one in 650 people (0.15%) have AT deficiency. Deep vein thrombosis of the lower limbs is the most common clinical symptom. Pregnancy further increases the risk of venous thromboembolism in thrombophilia carriers. Recombinant human AT gamma (rhAT-gamma) is marketed for the treatment of thrombophilia due to CAD; however, no clinical trials for Japanese CAD patients have been conducted.

Post-marketing surveillance was conducted at 22 sites in Japan from April 2016 to March 2022 to evaluate the safety and effectiveness of rhAT-gamma under clinical use conditions in CAD patients. Patients who had received rhAT-gamma for thrombophilia due to CAD were enrolled. The observation period for each patient was 12 months after treatment initiation or 28 days after the end of treatment.

During the study period, 28 patients were recruited. Of these, 22 patients (1 man, 21 women) comprised the safety and effectiveness population. The reasons for rhAT-gamma use overlapped, being surgery in 13.6% (3/22) of the patients, pregnancy in 86.4% (19/22), and others in 22.7% (5/22). rhAT-gamma was administered at 20–94 IU/kg once daily. In the safety evaluation, adverse events (AEs) and adverse drug reactions were observed in 31.8% (7/22) and 18.2% (4/22) of the patients, respectively. Serious AEs occurred in 9.1% (2/22) of the patients; no AEs resulted in death. In the effectiveness evaluation, rhAT-gamma was judged effective in all patients. AT activity increased in most patients, contributing to safe delivery outcomes in pregnant women. Although the data were limited, D-dimer levels decreased after rhAT-gamma administration.

rhAT-gamma was safe and tolerable in Japanese CAD patients, with an increase in AT activity confirmed in most patients. Among pregnant women with a higher risk of thrombosis, no thrombosis was observed before or after delivery, leading to safe childbirth.

University Hospital Medical Information Network; study ID, UMIN000050276; date of registration, 8 February 2023 (retrospectively registered).

The online version contains supplementary material available at 10.1186/s12959-026-00844-x.

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