抗エミシズマブ抗体とその臨床的意義

Emicizumab is licensed for treatment of people with hemophilia A (HA) of all ages, with and without factor (F)VIII inhibitors. It is well tolerated, and most of the treatment-related adverse events are of mild intensity and transient. As for other therapeutic proteins, the potential of emicizumab to induce anti-drug antibodies (ADAs) should be considered when a decrease in treatment efficacy is observed. Data from 7 phase 3/3b pivotal studies showed that 5.1% of treated patients developed ADAs, <1% being activity neutralizing. Among them, 1 case required discontinuation of emicizumab due to loss of treatment efficacy. To date, among several thousands of patients treated with emicizumab, 5 cases of ADAs requiring treatment discontinuation have been reported.

Monitoring anti-emicizumab antibodies in 67 subjects with congenital HA who switched to emicizumab prophylaxis from FVIII products or bypassing agents.

The anti-emicizumab antibodies were tested, depending on patient availability, at baseline and longitudinally at 5, 10, 20, and 50 weeks after the first dose, as well as when clinically required.

ADAs were detected in 4 of 67 cases (5.9%) on at least 2 occasions and were not necessarily associated to significant decreased emicizumab concentration, activated partial thromboplastin time prolongation or bleeding episodes. Only 1 of 4 ADA-positive patients required emicizumab discontinuation due to treatment failure.

The present findings confirm that the development of anti-emicizumab antibodies is a rare event, particularly those with neutralizing activity. Routine monitoring should be reserved only for patients with clinical manifestations of bleeding when therapy failure is suspected.