{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T07:59:47Z","timestamp":1771919987570,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Genentech Inc.- A Member of the Roche Group","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objectives: We compared patient-reported outcomes (PROs) in persons with hemophilia A (PwHA) by inhibitor status and prescribed treatment products. Methods: Hematology Utilization Group VIII study enrolled PwHA aged \u2265 2 years to collect PRO data via surveys. A clinical chart review documented the hemophilic severity, inhibitor level and treatment regimen. PROs were compared across inhibitor status and prescribed treatment products. Results: Among 85 enrolled PwHA, 9 (10.6%) had active inhibitors, 22 (25.9%) had tolerized inhibitors, and 54 (63.5%) had no inhibitors. The no-inhibitor group was significantly older (mean: 29.3 \u00b1 13.5 years) than the tolerized (16.3 \u00b1 9.5 years) and active inhibitor (21.9 \u00b1 19.1 years; p = 0.001) groups. A larger proportion of participants with active inhibitors (66.7%) and no inhibitors (53.7%) reported having bleeds in the previous month compared to those with tolerized inhibitors (22.7%, p = 0.02). After covariate adjustment for age and hemophilia severity, the tolerized inhibitor group showed the lowest estimated number of joint bleeds compared to those of the no inhibitor and active inhibitor groups (p = 0.08), and the highest EQ-5D index score (p = 0.09). Emicizumab users reported significantly fewer bleeds in the previous months than those who were prescribed standard or extended half-life factor VIII (33.3% vs. 58.6%, 64.3%, p = 0.04). Conclusions: Participants with active inhibitors experienced joint bleeding rates similar to those of participants without inhibitors, likely attributable to emicizumab use. Tolerized participants reported the fewest joint bleeds and highest quality-of-life scores, potentially reflecting younger age and possible greater prophylaxis adherence. Emicizumab was associated with lower bleed rates compared to standard or extended half-life factor VIII products.<\/jats:p>","DOI":"10.3390\/jcm15041517","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T08:38:39Z","timestamp":1771231119000},"page":"1517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Patient-Reported Outcomes with Hemophilia A Inhibitor Status and Treatment Product Type"],"prefix":"10.3390","volume":"15","author":[{"given":"Megan M.","family":"Ullman","sequence":"first","affiliation":[{"name":"Gulf States Hemophilia & Thrombophilia Center, University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilyn J.","family":"Manco-Johnson","sequence":"additional","affiliation":[{"name":"Hemophilia & Thrombosis Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9415-9543","authenticated-orcid":false,"given":"Jonathan C.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Bleeding & Clotting Disorders Institute, Dills Family Foundation Center for Research at BCDI, Peoria, IL 61614, USA"},{"name":"Departments of Pediatrics and Medicine, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1960-7323","authenticated-orcid":false,"given":"Nicole","family":"Crook","sequence":"additional","affiliation":[{"name":"The Center for Comprehensive Care & Diagnosis of Inherited Blood Disorders, Orange, CA 92868, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6859-6432","authenticated-orcid":false,"given":"Randall","family":"Curtis","sequence":"additional","affiliation":[{"name":"Factor VIII Computing, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7850-0027","authenticated-orcid":false,"given":"Judith R.","family":"Baker","sequence":"additional","affiliation":[{"name":"The Center for Comprehensive Care & Diagnosis of Inherited Blood Disorders, Orange, CA 92868, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0932-4979","authenticated-orcid":false,"given":"Joanne","family":"Wu","sequence":"additional","affiliation":[{"name":"Leonard D. Schaeffer Center for Health Policy and Economics, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael B.","family":"Nichol","sequence":"additional","affiliation":[{"name":"Leonard D. Schaeffer Center for Health Policy and Economics, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1542\/pir.2020-004143","article-title":"Hemophilia: The Past, the Present, and the Future","volume":"42","author":"Roberts","year":"2021","journal-title":"Pediatr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"897","DOI":"10.2147\/JBM.S325031","article-title":"Integrated Hemophilia Patient Care via a National Network of Care Centers in the United States: A Model for Rare Coagulation Disorders","volume":"12","author":"Valentino","year":"2021","journal-title":"J. Blood Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1055\/s-0042-1756188","article-title":"The More Recent History of Hemophilia Treatment","volume":"48","author":"Franchini","year":"2022","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2020001","DOI":"10.4084\/mjhid.2020.001","article-title":"Molecular Mechanisms of Inhibitor Development in Hemophilia","volume":"12","author":"Tieu","year":"2020","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/j.1365-2516.2011.02713.x","article-title":"Health care expenditures for Medicaid-covered males with haemophilia in the United States, 2008","volume":"18","author":"Guh","year":"2012","journal-title":"Haemophilia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1365-2516.2011.02692.x","article-title":"Healthcare expenditures for males with haemophilia and employer-sponsored insurance in the United States, 2008","volume":"18","author":"Guh","year":"2012","journal-title":"Haemophilia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/ajh.23957","article-title":"Impact of inhibitors on hemophilia A mortality in the United States","volume":"90","author":"Walsh","year":"2015","journal-title":"Am. J. Hem."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rocino, A., Franchini, M., and Coppola, A. (2017). Treatment and prevention of bleeds in haemophilia patients with inhibitors to factor VIII\/IX. J. Clin. Med., 6.","DOI":"10.3390\/jcm6040046"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/hae.12019","article-title":"Health-related quality of life in haemophilia patients with inhibitors and their caregivers","volume":"19","author":"Dekoven","year":"2013","journal-title":"Haemophilia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1182\/blood-2014-05-577643","article-title":"Toward optimal therapy for inhibitors in hemophilia","volume":"124","author":"Kempton","year":"2014","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/0304-3959(87)90161-8","article-title":"Acute and chronic pain in hemophilia","volume":"31","author":"Choiniere","year":"1987","journal-title":"Pain"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1111\/j.1365-2516.2011.02677.x","article-title":"Healthcare resource utilization among hemophilia A patients in the United States","volume":"18","author":"Valentino","year":"2012","journal-title":"Haemophilia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/ejh.13108","article-title":"The socioeconomic burden of patients affected by hemophilia with inhibitors","volume":"101","author":"Cortesi","year":"2018","journal-title":"Eur. J. Haematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/j.1365-2516.2006.01370.x","article-title":"Assessing the costs for clinical care of patients with high-responding factor VIII and IX inhibitors","volume":"12","author":"Ullman","year":"2006","journal-title":"Haemophilia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s13023-018-0929-9","article-title":"Inhibitor clinical burden of disease: A comparative analysis of the CHESS data","volume":"13","author":"Oladapo","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"545","DOI":"10.3324\/haematol.2019.232132","article-title":"Hemophilia therapy: The future has begun","volume":"105","author":"Mannucci","year":"2020","journal-title":"Haematologica"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/hae.13618","article-title":"The effect of emicizumab prophylaxis on health-related outcomes in persons with haemophilia A with inhibitors: HAVEN 1 Study","volume":"25","author":"Oldenburg","year":"2019","journal-title":"Haemophilia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1111\/hae.14363","article-title":"The effect of emicizumab prophylaxis on long-term, self-reported physical health in persons with haemophilia A without factor VIII inhibitors in the HAVEN 3 and HAVEN 4 studies","volume":"27","author":"Skinner","year":"2021","journal-title":"Haemophilia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1355-0691.2004.00881.x","article-title":"Utilization of care in haemophilia: A resource-based method for cost analysis from the Haemophilia Utilization Group Study (HUGS)","volume":"10","author":"Globe","year":"2004","journal-title":"Haemophilia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/j.1365-2516.2011.02595.x","article-title":"Haemophilia utilization group study\u2014Part Va (HUGS Va): Design, methods and baseline data","volume":"17","author":"Zhou","year":"2011","journal-title":"Haemophilia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3111\/13696998.2015.1016228","article-title":"Burden of illness: Direct and indirect costs among persons with hemophilia A in the United States","volume":"18","author":"Zhou","year":"2013","journal-title":"J. Med. Econ."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/j.jval.2017.04.017","article-title":"Economic Burden of Illness among Persons with Hemophilia B from HUGS Vb: Examining the Association of Severity and Treatment Regimens with Costs and Annual Bleed Rates","volume":"20","author":"Chen","year":"2017","journal-title":"Value Health"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1111\/j.1538-7836.2009.03318.x","article-title":"Health status and quality of life of elderly persons with severe hemophilia born before the advent of modern replacement therapy","volume":"7","author":"Siboni","year":"2009","journal-title":"J. Thromb. Haemost."},{"key":"ref_24","unstructured":"Keller, S., Yang, M., Evensen, C., and Cowans, T. (2017). ASCQ-Me User\u2019s Manual, American Institutes for Research."},{"key":"ref_25","unstructured":"(2024, January 05). EUROQOL. Available online: https:\/\/euroqol.org\/publications\/user-guides\/."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/00005650-200503000-00003","article-title":"US valuation of the EQ-5D health states: Development and testing of the D1 valuation model","volume":"43","author":"Shaw","year":"2005","journal-title":"Med. Care"},{"key":"ref_27","unstructured":"Cohen, J. (1988). Statistical Power Analysis for the Behavioral Sciences, Erlbaum. [2nd ed.]."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1097\/MLR.0b013e3181c162a2","article-title":"Using instrument-defined health state transitions to estimate minimally important differences for four preference-based health-related quality of life instruments","volume":"48","author":"Luo","year":"2010","journal-title":"Med. Care"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1080\/17474086.2022.2112171","article-title":"Real-world study of rurioctocog alfa pegol and emicizumab in US clinical practice among patients with hemophilia A","volume":"15","author":"Sun","year":"2022","journal-title":"Expert Rev. Hematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1182\/blood-2023-178007","article-title":"Clinical Outcomes of Noninhibitor Patients with Hemophilia a Switching from Prophylaxis with Factor VIII to Emicizumab: A Meta-Analysis of Real-World Evidence Studies","volume":"142","author":"Escobar","year":"2023","journal-title":"Blood"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/4\/1517\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T05:13:55Z","timestamp":1771910035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/4\/1517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,14]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jcm15041517"],"URL":"https:\/\/doi.org\/10.3390\/jcm15041517","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,14]]}}}