TY - JOUR
T1 - Natural history study of factor IX deficiency with focus on treatment and complications (B-Natural)
AU - Shapiro, Amy D
AU - Ragni, Margaret V
AU - Borhany, Munira
AU - Abajas, Yasmina L
AU - Tarantino, Michael D
AU - Holstein, Katharina
AU - Croteau, Stacy E
AU - Liesner, Riana
AU - Tarango, Cristina
AU - Carvalho, Manuela
AU - McGuinn, Catherine
AU - Funding, Eva
AU - Kempton, Christine L
AU - Bidlingmaier, Christoph
AU - Cohen, Alice
AU - Oldenburg, Johannes
AU - Kearney, Susan
AU - Knoll, Christine
AU - Kuriakose, Philip
AU - Acharya, Suchitra
AU - Reiss, Ulrike M
AU - Kulkarni, Roshni
AU - Witkop, Michelle
AU - Lethagen, Stefan
AU - Donfield, Sharyne
AU - LeBeau, Petra
AU - Berntorp, Erik
AU - Astermark, Jan
N1 - © 2020 John Wiley & Sons Ltd.
PY - 2021/1
Y1 - 2021/1
N2 - INTRODUCTION: Haemophilia B (HB) is less well studied than haemophilia A (HA); despite similarities between the two inherited bleeding disorders, important differences remain that require further research.AIM: B-Natural is a multi-centre, prospective, observational study of HB, designed to increase understanding of clinical manifestations, treatment, quality-of-life (QoL), inhibitor development, immune tolerance induction (ITI) outcome, renal function and create a biorepository for future investigations.METHODS: Participants include sibling pairs/groups without a current/history of inhibitors and singletons or siblings with a current/history of inhibitors followed for six months. Demographics, medical, social history and treatment were recorded. A physical examination including joint range of motion (ROM) was performed; QoL was assessed. Samples were collected for F9 gene mutation, HLA typing, non-inhibitory antibodies and renal function testing.RESULTS: Twenty-four centres enrolled 224 individuals from 107 families including 29 with current/history of inhibitors. Of these, 68, 30.4%, had severe (<1% FIX level of normal); 114, 50.9%, moderate (1%-5%); and 42, 18.8%, mild (>5-<40%) disease. At enrolment, 53.1% had 50 + exposure days to exogenous FIX. Comparison of joint scores showed significant (P < .05) differences between those with severe (with/without inhibitors), and those with moderate/mild disease. The majority with severe disease, 80.0% with current/history of inhibitors and 64.3% of those without, were treated with prophylaxis.CONCLUSION: B-Natural provides data supporting an increased understanding of HB and its impact throughout life. The need for optimal disease control to normalize physical and psychosocial outcomes is underscored, and further analyses will contribute to an increased understanding of critical issues in HB.
AB - INTRODUCTION: Haemophilia B (HB) is less well studied than haemophilia A (HA); despite similarities between the two inherited bleeding disorders, important differences remain that require further research.AIM: B-Natural is a multi-centre, prospective, observational study of HB, designed to increase understanding of clinical manifestations, treatment, quality-of-life (QoL), inhibitor development, immune tolerance induction (ITI) outcome, renal function and create a biorepository for future investigations.METHODS: Participants include sibling pairs/groups without a current/history of inhibitors and singletons or siblings with a current/history of inhibitors followed for six months. Demographics, medical, social history and treatment were recorded. A physical examination including joint range of motion (ROM) was performed; QoL was assessed. Samples were collected for F9 gene mutation, HLA typing, non-inhibitory antibodies and renal function testing.RESULTS: Twenty-four centres enrolled 224 individuals from 107 families including 29 with current/history of inhibitors. Of these, 68, 30.4%, had severe (<1% FIX level of normal); 114, 50.9%, moderate (1%-5%); and 42, 18.8%, mild (>5-<40%) disease. At enrolment, 53.1% had 50 + exposure days to exogenous FIX. Comparison of joint scores showed significant (P < .05) differences between those with severe (with/without inhibitors), and those with moderate/mild disease. The majority with severe disease, 80.0% with current/history of inhibitors and 64.3% of those without, were treated with prophylaxis.CONCLUSION: B-Natural provides data supporting an increased understanding of HB and its impact throughout life. The need for optimal disease control to normalize physical and psychosocial outcomes is underscored, and further analyses will contribute to an increased understanding of critical issues in HB.
KW - factor IX deficiency
KW - FIX inhibitors
KW - haemophilia B
KW - joint range-of-motion
KW - quality-of-life
KW - treatment
UR - http://www.scopus.com/inward/record.url?scp=85097099778&partnerID=8YFLogxK
U2 - 10.1111/hae.14139
DO - 10.1111/hae.14139
M3 - Journal article
C2 - 33278853
SN - 1351-8216
VL - 27
SP - 49
EP - 59
JO - Haemophilia
JF - Haemophilia
IS - 1
ER -