Johnny Mahlangu1, Johannes Oldenburg2, Michael U Callaghan3, Midori Shima4, Elena Santagostino5, Maggie Moore6, Michael Recht7, Claudia Garcia8, Renchi Yang9, Michaela Lehle10, Harrison Macharia10, Elina Asikanius10, Gallia G Levy11, Rebecca Kruse-Jarres6. 1. Haemophilia Comprehensive Care Centre, Faculty of Health Sciences, University of the Witwatersrand and NHLS, Johannesburg, South Africa. 2. Department of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany. 3. Children's Hospital of Michigan, Detroit, Michigan. 4. Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan. 5. Fondazione IRCCS Ca' Granda Foundation, Ospedale Maggiore Policlinico, Milan, Italy. 6. Washington Center for Bleeding Disorders at Bloodworks Northwest, Seattle, Washington. 7. Oregon Health & Science University, Portland, Oregon. 8. Haematology Department, Hospital Mexico, San Jose, Costa Rica. 9. Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China. 10. F. Hoffmann-La Roche Ltd, Basel, Switzerland. 11. Genentech, Inc., South San Francisco, California.
Abstract
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.
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.
Authors: B M Reipert; B Gangadharan; C J Hofbauer; V Berg; H Schweiger; J Bowen; J Blatny; K Fijnvandraat; E S Mullins; J Klintman; C Male; C McGuinn; S L Meeks; V C Radulescu; M V Ragni; M Recht; A D Shapiro; J M Staber; H M Yaish; E Santagostino; D L Brown Journal: Blood Adv Date: 2020-11-24
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