Final Analysis Results from the AGEHA Study: Emicizumab Prophylaxis for Acquired Hemophilia A with or without Immunosuppressive Therapy

Midori Shima; Nobuaki Suzuki; Hidekazu Nishikii; Kagehiro Amano; Yoshiyuki Ogawa; Ryota Kobayashi; Ryoto Ozaki; Koichiro Yoneyama; Narumi Mizuno; Emiko Sakaida; Makoto Saito; Takashi Okamura; Toshihiro Ito; Norimichi Hattori; Satoshi Higasa; Yoshinobu Seki; Keiji Nogami

doi:10.1055/a-2384-3585

Thrombosis and Haemostasis, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Thromb Haemost 2025; 125(05): 449-459
DOI: 10.1055/a-2384-3585

Coagulation and Fibrinolysis

Final Analysis Results from the AGEHA Study: Emicizumab Prophylaxis for Acquired Hemophilia A with or without Immunosuppressive Therapy

Midori Shima

¹Thrombosis and Hemostasis Research Center, Nara Medical University, Kashihara, Japan

²Department of Pediatrics, Nara Medical University, Kashihara, Japan

,

Nobuaki Suzuki

³Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan

,

Hidekazu Nishikii

⁴Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

,

Kagehiro Amano

⁵Department of Laboratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan

,

Yoshiyuki Ogawa

⁶Department of Hematology, Gunma University Graduate School of Medicine, Maebashi, Japan

,

Ryota Kobayashi

⁷Chugai Pharmaceutical Co., Ltd., Tokyo, Japan

,

Ryoto Ozaki

⁷Chugai Pharmaceutical Co., Ltd., Tokyo, Japan

,

Koichiro Yoneyama

⁷Chugai Pharmaceutical Co., Ltd., Tokyo, Japan

,

Narumi Mizuno

⁷Chugai Pharmaceutical Co., Ltd., Tokyo, Japan

,

Emiko Sakaida

⁸Department of Hematology, Chiba University Hospital, Chiba, Japan

,

Makoto Saito

⁹Blood Disorders Center, Aiiku Hospital, Sapporo, Japan

,

Takashi Okamura

¹⁰Department of Hematology, St. Mary's Hospital, Kurume, Japan

,

Toshihiro Ito

¹¹Department of Infectious Diseases, National Hospital Organization Sendai Medical Center, Sendai, Japan

,

Norimichi Hattori

¹²Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan

,

Satoshi Higasa

¹³Department of Hematology, Hyogo College of Medicine Hospital, Nishinomiya, Japan

,

Yoshinobu Seki

¹⁴Department of Hematology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami-uonuma, Japan

,

Keiji Nogami

²Department of Pediatrics, Nara Medical University, Kashihara, Japan

› Institutsangaben

Abstract

Background

Primary analysis of the phase III AGEHA study suggested a favorable benefit–risk profile for emicizumab prophylaxis in patients with acquired hemophilia A (PwAHA); however, only patients undergoing immunosuppressive therapy (IST; Cohort 1) were included.

Objectives

To present final analysis results of AGEHA, including data on IST-ineligible patients (Cohort 2) and on long-term prophylaxis with emicizumab.

Methods

For patients in both Cohorts 1 and 2, emicizumab was administered subcutaneously at 6 mg/kg on Day 1, 3 mg/kg on Day 2, and 1.5 mg/kg once weekly from Day 8 onward.

Results

Twelve patients (Cohort 1) and two patients (Cohort 2) were enrolled. Duration of emicizumab treatment was 8 to 639 days (median: 44.5 days) in Cohort 1 and 64 and 450 days in Cohort 2. In both cohorts, no major bleeds were observed after initial emicizumab administration. Six patients started their first rehabilitation sessions during emicizumab treatment and no rehabilitation-related bleeds occurred. Twenty-three surgeries were performed under emicizumab prophylaxis and there were no bleeds related to surgeries. Although asymptomatic deep vein thrombosis was reported in one patient in the primary analysis, no other thrombotic events occurred thereafter. Two patients developed anti-emicizumab antibodies, one of whom showed accelerated emicizumab clearance. Tailored IST approaches (delayed initiation, no use, or reduced dose) were successfully executed in three patients undergoing emicizumab prophylaxis.

Conclusion

These results suggest that emicizumab prophylaxis has a favorable benefit–risk profile in PwAHA regardless of eligibility for IST.

Keywords

Factor VIII deficiency, acquired - long-term care - immunosuppressive therapy - rehabilitation - surgery

Volltext

Referenzen

References
1 Collins PW, Hirsch S, Baglin TP. et al; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood 2007; 109 (05) 1870-1877
2 Tiede A, Collins P, Knoebl P. et al. International recommendations on the diagnosis and treatment of acquired hemophilia A. Haematologica 2020; 105 (07) 1791-1801
3 Tiede A, Klamroth R, Scharf RE. et al. Prognostic factors for remission of and survival in acquired hemophilia A (AHA): results from the GTH-AH 01/2010 study. Blood 2015; 125 (07) 1091-1097
4 Knoebl P, Marco P, Baudo F. et al; EACH2 Registry Contributors. Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). J Thromb Haemost 2012; 10 (04) 622-631
5 Sampei Z, Igawa T, Soeda T. et al. Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity. PLoS One 2013; 8 (02) e57479
6 Callaghan MU, Negrier C, Paz-Priel I. et al. Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. Blood 2021; 137 (16) 2231-2242
7 Krumb E, Fijnvandraat K, Makris M. et al. Adoption of emicizumab (Hemlibra®) for hemophilia A in Europe: data from the 2020 European Association for Haemophilia and Allied Disorders survey. Haemophilia 2021; 27 (05) 736-743
8 Muto A, Yoshihashi K, Takeda M. et al. Anti-factor IXa/X bispecific antibody (ACE910): hemostatic potency against ongoing bleeds in a hemophilia A model and the possibility of routine supplementation. J Thromb Haemost 2014; 12 (02) 206-213
9 Muto A, Yoshihashi K, Takeda M. et al. Anti-factor IXa/X bispecific antibody ACE910 prevents joint bleeds in a long-term primate model of acquired hemophilia A. Blood 2014; 124 (20) 3165-3171
10 Shima M, Amano K, Ogawa Y. et al. A prospective, multicenter, open-label phase III study of emicizumab prophylaxis in patients with acquired hemophilia A. J Thromb Haemost 2023; 21 (03) 534-545
11 Tiede A, Hart C, Knöbl P. et al. Emicizumab prophylaxis in patients with acquired haemophilia A (GTH-AHA-EMI): an open-label, single-arm, multicentre, phase 2 study. Lancet Haematol 2023; 10 (11) e913-e921
12 Santagostino E, Lentz SR, Misgav M. et al. Safety and efficacy of turoctocog alfa (NovoEight®) during surgery in patients with haemophilia A: results from the multinational guardian™ clinical trials. Haemophilia 2015; 21 (01) 34-40
13 Anderson MA, Ben-Menachem T, Gan SI. et al; ASGE Standards of Practice Committee. Management of antithrombotic agents for endoscopic procedures. Gastrointest Endosc 2009; 70 (06) 1060-1070
14 Ogawa Y, Yanagisawa K, Naito C. et al. Overshoot of FVIII activity in patients with acquired hemophilia A who achieve complete remission. Int J Hematol 2020; 111 (04) 544-549
15 Pasca S, Zanon E, Mannucci PM, Peyvandi F. Emicizumab in acquired hemophilia A: pros and cons of a new approach to the prevention and treatment of bleeding. Blood Transfus 2023; 21 (06) 549-556
16 Jenkins PV, Rawley O, Smith OP, O'Donnell JS. Elevated factor VIII levels and risk of venous thrombosis. Br J Haematol 2012; 157 (06) 653-663
17 Goto M, Haga N, Yokota K, Takamizawa K, Takedani H. A successful physiotherapy management case of a patient with acquired haemophilia A prior to factor VIII inhibitor eradication. Haemophilia 2016; 22 (03) e228-e231
18 Tedeschi R. Acquired haemophilia A in an elderly patient: a case report of functional recovery through physiotherapy. Int J Surg Case Rep 2023; 110: 108769
19 Schmitt C, Emrich T, Chebon S. et al. Low immunogenicity of emicizumab in persons with haemophilia A. Haemophilia 2021; 27 (06) 984-992
20 Pizano-Martinez O, Mendieta-Condado E, Vázquez-Del Mercado M. et al. Anti-drug antibodies in the biological therapy of autoimmune rheumatic diseases. J Clin Med 2023; 12 (09) 3271

Zusatzmaterial

Supplementary Material