TY - JOUR
T1 - Bleeding events and safety outcomes in persons with haemophilia A with inhibitors
T2 - A prospective, multi-centre, non-interventional study
AU - Mahlangu, Johnny
AU - Oldenburg, Johannes
AU - Callaghan, Michael U.
AU - Shima, Midori
AU - Santagostino, Elena
AU - Moore, Maggie
AU - Recht, Michael
AU - Garcia, Claudia
AU - Yang, Renchi
AU - Lehle, Michaela
AU - Macharia, Harrison
AU - Asikanius, Elina
AU - Levy, Gallia G.
AU - Kruse-Jarres, Rebecca
N1 - Funding Information:
This study was sponsored by F. Hoffmann‐La Roche Ltd. Medical writing assistance for this manuscript was provided by Daniella Babu, PhD, of Envision Pharma Group, and funded by F. Hoffmann‐ La Roche Ltd.
Publisher Copyright:
© 2018 John Wiley & Sons Ltd
PY - 2018/11
Y1 - 2018/11
N2 - Introduction: Prospectively collected, real-world data on bleeds, haemophilic treatment and safety outcomes in persons with haemophilia A (PwHA) with factor VIII (FVIII) inhibitors are limited. A prospective, global, multi-centre, non-interventional study (NIS; NCT02476942) collected detailed real-world data in PwHA treated per local routine clinical practice. Aim: To characterize bleeding rates, haemophilic treatment practices, prophylaxis adherence and adverse events (AEs) in adult/adolescent PwHA with inhibitors in the NIS. Methods: Participants aged ≥12 years with congenital haemophilia A/documented high-titre FVIII inhibitor history were enrolled. Participants remained on their usual treatment; no interventions were applied. Results: Overall, 103 PwHA with inhibitors enrolled, (median [range] age 31 [12-75] years) and were monitored for median (range) 26.0 (4.1-69.6) weeks. In the episodic (n = 75) and prophylactic (n = 28) treatment groups, respectively, 1244 and 325 bleeds were reported, and 528 (42.4%) and 104 (32.0%) were not treated; annualized bleeding rates (ABRs; 95% confidence interval) were 18.6 (15.2-22.8) and 14.9 (10.5-21.2) for treated bleeds, and 32.7 (27.3-39.1) and 25.0 (18.4-34.0) for all bleeds. Coagulation products used included activated prothrombin complex concentrate (aPCC) and/or recombinant activated FVII. Among participants prescribed aPCC prophylaxis, 35.0% adhered to both prescribed frequency of aPCC administration and prescribed dose. Serious AEs of haemarthrosis and muscle haemorrhage were reported; most common AEs were arthralgia, viral upper respiratory tract infection and pyrexia. Conclusions: ABRs (treated bleeds and all bleeds) remain high on standard treatment; this prospective NIS demonstrates the need for more effective treatments for PwHA with inhibitors to reduce/prevent bleeds, with potential to improve prophylaxis adherence and further improve outcomes.
AB - Introduction: Prospectively collected, real-world data on bleeds, haemophilic treatment and safety outcomes in persons with haemophilia A (PwHA) with factor VIII (FVIII) inhibitors are limited. A prospective, global, multi-centre, non-interventional study (NIS; NCT02476942) collected detailed real-world data in PwHA treated per local routine clinical practice. Aim: To characterize bleeding rates, haemophilic treatment practices, prophylaxis adherence and adverse events (AEs) in adult/adolescent PwHA with inhibitors in the NIS. Methods: Participants aged ≥12 years with congenital haemophilia A/documented high-titre FVIII inhibitor history were enrolled. Participants remained on their usual treatment; no interventions were applied. Results: Overall, 103 PwHA with inhibitors enrolled, (median [range] age 31 [12-75] years) and were monitored for median (range) 26.0 (4.1-69.6) weeks. In the episodic (n = 75) and prophylactic (n = 28) treatment groups, respectively, 1244 and 325 bleeds were reported, and 528 (42.4%) and 104 (32.0%) were not treated; annualized bleeding rates (ABRs; 95% confidence interval) were 18.6 (15.2-22.8) and 14.9 (10.5-21.2) for treated bleeds, and 32.7 (27.3-39.1) and 25.0 (18.4-34.0) for all bleeds. Coagulation products used included activated prothrombin complex concentrate (aPCC) and/or recombinant activated FVII. Among participants prescribed aPCC prophylaxis, 35.0% adhered to both prescribed frequency of aPCC administration and prescribed dose. Serious AEs of haemarthrosis and muscle haemorrhage were reported; most common AEs were arthralgia, viral upper respiratory tract infection and pyrexia. Conclusions: ABRs (treated bleeds and all bleeds) remain high on standard treatment; this prospective NIS demonstrates the need for more effective treatments for PwHA with inhibitors to reduce/prevent bleeds, with potential to improve prophylaxis adherence and further improve outcomes.
KW - blood coagulation factor inhibitors
KW - factor VIII
KW - haemophilia A
KW - non-interventional study
KW - observational study
KW - prospective study
UR - http://www.scopus.com/inward/record.url?scp=85054600093&partnerID=8YFLogxK
U2 - 10.1111/hae.13612
DO - 10.1111/hae.13612
M3 - Article
C2 - 30295389
AN - SCOPUS:85054600093
SN - 1351-8216
VL - 24
SP - 921
EP - 929
JO - Haemophilia
JF - Haemophilia
IS - 6
ER -