Emicizumab is Efficacious in People with Hemophilia A with Comorbidities Aged ≥50 Years: Analysis of 4 Phase III Trials

Overview

Journal Res Pract Thromb Haemost

Publisher Elsevier

Date 2024 May 24

PMID 38783987

Authors

Victor Jimenez-Yuste

Johannes Oldenburg

Eunice Tzeng

Elise Lim

Fabian Sanabria

Johnny Mahlangu

Affiliations

Soon will be listed here.

Abstract

Background: The treatment of older people with hemophilia A (HA) can be complicated by comorbidities.

Objectives: This post hoc analysis evaluates the efficacy and safety of emicizumab in people with HA aged ≥50 years with cardiovascular (CV) risk factors or HIV and/or hepatitis C virus (HCV) infection.

Methods: The HAVEN 1 (NCT02622321), HAVEN 3 (NCT02847637), HAVEN 4 (NCT03020160), and STASEY (NCT03191799) studies enrolled adults/adolescents with severe HA. Participants were categorized as having a comorbidity if they had any CV risk factors (including history of CV disease, hypertension, diabetes, hyperlipidemia, prior stroke, or obesity), HIV, and/or HCV infection. Efficacy and safety outcomes were compared by age (<50 vs ≥50 years).

Results: Of 504 participants at data cutoff, 408 were aged <50 years and 96 were aged ≥50 years. In people with HA aged <50 years, 26.7% had ≥1 CV risk factor and 29.4% had HIV and/or HCV infection. In people with HA aged ≥50 years, 72.9% had ≥1 CV risk factor and 74.0% had HIV and/or HCV infection. The mean (95% CI) annualized bleed rate for treated bleeds was 1.29 (0.07-6.06) for people with HA aged <50 years and 1.82 (0.19-6.93) for people with HA aged ≥50 years. No significant differences in annualized bleed rates were observed for those with comorbidities compared with those without. Safety outcomes were similar regardless of age.

Conclusion: This pooled analysis suggests that emicizumab efficacy and safety in people with HA aged ≥50 years with CV and HIV/HCV comorbidities were consistent with those in people with HA aged <50 years enrolled in the HAVEN 1, 3, and 4 and STASEY studies.

References

Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe S . WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020; 26 Suppl 6:1-158. DOI: 10.1111/hae.14046. View

Kempton C, Makris M, Holme P . Management of comorbidities in haemophilia. Haemophilia. 2020; 27 Suppl 3:37-45. DOI: 10.1111/hae.14013. View

Mannucci P, Schutgens R, Santagostino E, Mauser-Bunschoten E . How I treat age-related morbidities in elderly persons with hemophilia. Blood. 2009; 114(26):5256-63. DOI: 10.1182/blood-2009-07-215665. View

Tuinenburg A, Rutten A, Kavousi M, Leebeek F, Ypma P, Laros-van Gorkom B . Coronary artery calcification in hemophilia A: no evidence for a protective effect of factor VIII deficiency on atherosclerosis. Arterioscler Thromb Vasc Biol. 2011; 32(3):799-804. DOI: 10.1161/ATVBAHA.111.238162. View

Negrier C, Mahlangu J, Lehle M, Chowdary P, Catalani O, Bernardi R . Emicizumab in people with moderate or mild haemophilia A (HAVEN 6): a multicentre, open-label, single-arm, phase 3 study. Lancet Haematol. 2023; 10(3):e168-e177. DOI: 10.1016/S2352-3026(22)00377-5. View

Kitazawa T, Esaki K, Tachibana T, Ishii S, Soeda T, Muto A . Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to bridge the antigens. Thromb Haemost. 2017; 117(7):1348-1357. PMC: 6292136. DOI: 10.1160/TH17-01-0030. View

van der Valk P, Makris M, Fischer K, Tait R, Chowdary P, Collins P . Reduced cardiovascular morbidity in patients with hemophilia: results of a 5-year multinational prospective study. Blood Adv. 2021; 6(3):902-908. PMC: 8945305. DOI: 10.1182/bloodadvances.2021005260. View

Sharathkumar A, Soucie J, Trawinski B, Greist A, Shapiro A . Prevalence and risk factors of cardiovascular disease (CVD) events among patients with haemophilia: experience of a single haemophilia treatment centre in the United States (US). Haemophilia. 2011; 17(4):597-604. DOI: 10.1111/j.1365-2516.2010.02463.x. View

Chang C, Li T, Cheng S, Pan R, Cheng C, Wang H . Obesity and overweight in patients with hemophilia: Prevalence by age, clinical correlates, and impact on joint bleeding. J Chin Med Assoc. 2019; 82(4):289-294. DOI: 10.1097/JCMA.0000000000000047. View

10.

Fransen van de Putte D, Fischer K, Makris M, Tait R, Chowdary P, Collins P . Unfavourable cardiovascular disease risk profiles in a cohort of Dutch and British haemophilia patients. Thromb Haemost. 2012; 109(1):16-23. DOI: 10.1160/TH12-05-0332. View

11.

Chow C, Teo K, Rangarajan S, Islam S, Gupta R, Avezum A . Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries. JAMA. 2013; 310(9):959-68. DOI: 10.1001/jama.2013.184182. View

12.

Young G, Liesner R, Chang T, Sidonio R, Oldenburg J, Jimenez-Yuste V . A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors. Blood. 2019; 134(24):2127-2138. PMC: 6908828. DOI: 10.1182/blood.2019001869. View

13.

Jenkins P, Rawley O, Smith O, ODonnell J . Elevated factor VIII levels and risk of venous thrombosis. Br J Haematol. 2012; 157(6):653-63. DOI: 10.1111/j.1365-2141.2012.09134.x. View

14.

Garg S, Hoenig M, Edwards E, Bliss C, Heeren T, Tumilty S . Incidence and predictors of acute kidney injury in an urban cohort of subjects with HIV and hepatitis C virus coinfection. AIDS Patient Care STDS. 2011; 25(3):135-41. PMC: 3101898. DOI: 10.1089/apc.2010.0104. View

15.

Shapiro S, Benson G, Evans G, Harrison C, Mangles S, Makris M . Cardiovascular disease in hereditary haemophilia: The challenges of longevity. Br J Haematol. 2022; 197(4):397-406. PMC: 9306870. DOI: 10.1111/bjh.18085. View

16.

Blair H . Emicizumab: A Review in Haemophilia A. Drugs. 2019; 79(15):1697-1707. DOI: 10.1007/s40265-019-01200-2. View

17.

Jimenez-Yuste V, Peyvandi F, Klamroth R, Castaman G, Shanmukhaiah C, Rangarajan S . Safety and efficacy of long-term emicizumab prophylaxis in hemophilia A with factor VIII inhibitors: A phase 3b, multicenter, single-arm study (STASEY). Res Pract Thromb Haemost. 2022; 6(8):e12837. PMC: 9663319. DOI: 10.1002/rth2.12837. View

18.

Dhingra R, Vasan R . Age as a risk factor. Med Clin North Am. 2012; 96(1):87-91. PMC: 3297980. DOI: 10.1016/j.mcna.2011.11.003. View

19.

Manco-Johnson M, Lundin B, Funk S, Peterfy C, Raunig D, Werk M . Effect of late prophylaxis in hemophilia on joint status: a randomized trial. J Thromb Haemost. 2017; 15(11):2115-2124. DOI: 10.1111/jth.13811. View

20.

Franchini M, Mannucci P . Past, present and future of hemophilia: a narrative review. Orphanet J Rare Dis. 2012; 7:24. PMC: 3502605. DOI: 10.1186/1750-1172-7-24. View