Reappearance of inhibitor in a tolerized patient with severe haemophilia A during FVIII‐free emicizumab therapy

Capdevila, Ladislas; Borgel, Delphine; Lasne, Dominique; Lacroix‐Desmazes, Sébastien; Desvages, Maximilien; Delignat, Sandrine; Bally, Cécile; Frenzel, Laurent; Harroche, Annie

doi:10.1111/hae.14334

Cited by 7 publications

(5 citation statements)

References 11 publications

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“…To our note, a mild elevation of inhibitor titer was observed (from 22.9 to 28.9 BU) at the fifth infusion of emicizumab in PN-08 although his FVIII infusion had been stopped for 5 weeks. Capdevila et al reported a case with recurrence of FVIII inhibitor although no FVIII product was used ( 15 ). Due to the lack of its mechanism, further study should investigate this phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Real-world experience of emicizumab prophylaxis in young children with hemophilia A: retrospective data from China

Liu

Huang

et al. 2022

Front. Pediatr.

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BackgroundAs a new non-factor therapy for hemophilia A (HA), real-world study of emicizumab is still scarce. This study aimed to investigate the real-world use of emicizumab in Chinese boys with HA.MethodsPatients with moderate or severe HA were enrolled at Beijing Children's Hospital. They take emicizumab weekly (3 mg/kg) for a month and then went into a maintenance period with a different dosing regimen. After obtaining platelet-poor plasma at end of the loading period and during the maintenance period, coagulation ability and FVIII inhibitor were determined using human and bovine chromogenic Bethesda assay. Patients' bleeding rates were calculated through patients' records from 24 weeks before to at least 6 months after the switch (to emicizumab).ResultIn total, 13 pediatric patients with HA (severe: moderate = 11:2) were enrolled in this study. The patients' age was 3.51 (0.73–6.65) years. Eight had FVIII inhibitors at enrollment and one of them developed FVIII inhibitors again during the switch. The coagulation level of the maintenance period was 19.6 (13.5–32.8) IU/dL (N = 10). The median dose of each emicizumab injection was 2.7 (1.3–3.8) mg/kg and the monthly consumption of emicizumab was 5.2 (3.2–6.8) mg/kg/month. After switching to emicizumab, reduced annualized bleeding rate (ABR) [0.5 (0–4) vs. 4 (0–18), P < 0.01], annualized joint bleeding rate (AJBR) [0 (0–1.1) vs. 1.0 (0–12), P < 0.01], and annualized spontaneous bleeding rate (ASBR) [0 (0–1) vs. 2.0 (0–18), P < 0.01] were observed. In patients with or without FVIII inhibitor, similar ABR [0.33 (0–4) vs. 0.5 (0–3), P = 0.78], AJBR [0 (0–1.1) vs. 0 (0–0.5), P = 0.63], and ASBR [0 (0–1) vs. 0 (0–1.5), P = 0.73] were also noticed. Five inhibitor-positive patients (at enrollment) all had their inhibitor titer reduced. In addition, all target joints vanished after switching to emicizumab.ConclusionEmicizumab could reduce bleeds in pediatric patients with/without FVIII inhibitors and eliminate target joints.

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Section: Discussionmentioning

confidence: 99%

Real-world experience of emicizumab prophylaxis in young children with hemophilia A: retrospective data from China

Liu

Huang

et al. 2022

Front. Pediatr.

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“…Additionally, Capdevila et al. described the reappearance of inhibitors after emicizumab initiation and FVIII withdrawal in an adult patient 28 . In contrast, among seven out of 51 HA patients with complete tolerance to inhibitor with ITI, one patient had a low‐titre inhibitor recurrence that disappeared without interventions 29 .…”

Section: Discussionmentioning

confidence: 99%

Efficacy, safety and cost of emicizumab prophylaxis in haemophilia A patients with inhibitors: A nationwide observational study in Taiwan

Shen,

Chou,

Chiou

et al. 2023

Haemophilia

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IntroductionEmicizumab mimicking the cofactor function of activated factor VIII (FVIII) restores haemostasis.MethodsThis nationwide observational study aimed to retrospectively investigate efficacy, safety, and cost in 1 year before and up to 3 years after emicizumab prophylaxis for haemophilia A (HA) patients with FVIII inhibitors.Results and discussionA total of 39 severe HA patients with a median age of 23.0 years were enrolled. The median historical peak FVIII inhibitor titre was 174.2 BU/mL with an interquartile range of 56.5–578.8 BU/mL. The median annualized bleeding rate reduced from 24 to 0 events in the first year after emicizumab prophylaxis (p < .01) and sustained in the second and third years. The median annualized joint bleeding rate reduced to 0 and maintained up to 3 years (p < .01). Twenty‐seven patients (69.2%) had target joints before emicizumab prophylaxis and only seven patients (17.9%) of them had target joints after prophylaxis. Medical costs, including cost of haemostatic therapy, frequency of outpatient department visits, emergency room visits and hospital admission, were significantly reduced after emicizumab prophylaxis (p < .01). FVIII inhibitor titre decreased after emicizumab prophylaxis. Overall, three (7.7%) patients experienced 202 grade 1 drug‐related adverse events after emicizumab prophylaxis. No serious adverse events were reported during emicizumab prophylaxis period. The adherence to emicizumab prophylaxis was 100% up to 3 years.ConclusionsHA patients with FVIII inhibitors treated with emicizumab prophylaxis resulted in a significant reduction in treated bleeds and associated costs. No new safety events were observed.

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“…This was interpreted as possibly being due to the remaining presence of non-neutralizing anti-FVIII IgG1 antibodies before the switch. 8 Of 15 subjects with measurable inhibitors at different time-points during study course, only one had no detectable anti-FVIII antibodies measured by ELISA, which is suggestive of low affinity neutralizing antibodies. His lupus anticoagulant screening was negative.…”

Section: Switching To Emicizumab: a Prospective Surveillance Study In...mentioning

confidence: 91%

Switching to emicizumab: A prospective surveillance study in haemophilia A subjects with inhibitors

et al. 2022

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Reappearance of inhibitor in a tolerized patient with severe haemophilia A during FVIII‐free emicizumab therapy

Cited by 7 publications

References 11 publications

Real-world experience of emicizumab prophylaxis in young children with hemophilia A: retrospective data from China

Real-world experience of emicizumab prophylaxis in young children with hemophilia A: retrospective data from China

Efficacy, safety and cost of emicizumab prophylaxis in haemophilia A patients with inhibitors: A nationwide observational study in Taiwan

Switching to emicizumab: A prospective surveillance study in haemophilia A subjects with inhibitors

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