The burden of illness of patients with paroxysmal nocturnal haemoglobinuria receiving C5 inhibitors: clinical outcomes and medical encounters from the patient perspective

References

• Hill A, DeZern AE, Kinoshita T, et al. Paroxysmal nocturnal haemoglobinuria. Nat Rev Dis Primers. 2017 Nov;3:17028. doi:10.1038/nrdp.2017.28.
   PubMed Web of Science ®Google Scholar
• Schrezenmeier H, Röth A, Araten DJ, et al. Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the international PNH registry. Ann Hematol. 2020 Jul;99(7):1505–1514. doi:10.1007/s00277-020-04052-z.
   PubMed Web of Science ®Google Scholar
• Devalet B, Mullier F, Chatelain B, et al. Pathophysiology, diagnosis, and treatment of paroxysmal nocturnal hemoglobinuria: a review. Eur J Haematol. 2015 Sep;95(3):190–198. doi:10.1111/ejh.12543.
   PubMed Web of Science ®Google Scholar
• Orphanet: Paroxysmal nocturnal hemoglobinuria [Internet]. Orphanet Journal of Rare Diseases. [cited 2021 Mar 24]. Available from: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=447.
   Google Scholar
• Schrezenmeier H, Muus P, Socié G, et al. Baseline characteristics and disease burden in patients in the international paroxysmal nocturnal hemoglobinuria registry. Haematologica. 2014 May;99(5):922–929. doi:10.3324/haematol.2013.093161.
   PubMed Web of Science ®Google Scholar
• Cheng WY, Sarda SP, Mody-Patel N, et al. Real-world healthcare resource utilization (HRU) and costs of patients with paroxysmal nocturnal hemoglobinuria (PNH) receiving eculizumab in a US population. Adv Ther. 2021 Aug;38(8):4461–4479. doi:10.1007/s12325-021-01825-4.
   PubMed Web of Science ®Google Scholar
• Bektas M, Copley-Merriman C, Khan S, et al. Paroxysmal nocturnal hemoglobinuria: patient journey and burden of disease. J Manag Care Spec Pharm. 2020 Dec;26(12-b Suppl):S8–S14. doi:10.18553/jmcp.2020.26.12-b.s8.
   PubMed Web of Science ®Google Scholar
• Tomazos I, Sierra JR, Johnston KM, et al. Cost burden of breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria receiving ravulizumab versus eculizumab. Hematology. 2020 Dec;25(1):327–334. doi:10.1080/16078454.2020.1807226.
   PubMed Web of Science ®Google Scholar
• Hillmen P, Lewis SM, Bessler M, et al. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995 Nov;333(19):1253–1258. doi:10.1056/nejm199511093331904.
   PubMed Web of Science ®Google Scholar
• Korkama ES, Armstrong AE, Jarva H, et al. Spontaneous remission in paroxysmal nocturnal hemoglobinuria—return to health or transition into malignancy? Front Immunol. 2018;9:1749. doi:10.3389/fimmu.2018.01749.
   PubMed Web of Science ®Google Scholar
• Bektas M, Copley-Merriman C, Khan S, et al. Paroxysmal nocturnal hemoglobinuria: current treatments and unmet needs. J Manag Care Spec Pharm. 2020 Dec;26(12-b Suppl):S14–S20. doi:10.18553/jmcp.2020.26.12-b.s14.
   PubMed Web of Science ®Google Scholar
• Risitano AM, Marotta S, Ricci P, et al. Anti-complement treatment for paroxysmal nocturnal hemoglobinuria: time for proximal complement inhibition? A position paper from the SAAWP of the EBMT. Front Immunol. 2019;10:1157. doi:10.3389/fimmu.2019.01157.
   PubMed Web of Science ®Google Scholar
• Hillmen P, Hall C, Marsh JC, et al. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2004 Feb;350(6):552–559. doi:10.1056/NEJMoa031688.
   PubMed Web of Science ®Google Scholar
• Kelly RJ, Hill A, Arnold LM, et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood. 2011 Jun;117(25):6786–6792. doi:10.1182/blood-2011-02-333997.
   PubMed Web of Science ®Google Scholar
• Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood. 2013 Jun;121(25):4985–4996. doi:10.1182/blood-2012-09-311381.
   PubMed Web of Science ®Google Scholar
• Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014 Oct;124(18):2804–2811. doi:10.1182/blood-2014-02-522128.
   PubMed Web of Science ®Google Scholar
• Brodsky RA. Stem cell transplantation for paroxysmal nocturnal hemoglobinuria. Haematologica. 2010 Jun;95(6):855–856. doi:10.3324/haematol.2010.023176.
   PubMed Web of Science ®Google Scholar
• Alexion. Solirus (eculizumab) [package insert]. U.S. Food and Drug Administration website. [cited 2021 Aug]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125166s422lbl.pdf.
   Google Scholar
• Alexion. Soliris (eculizumab) [package leaflet]. European Medicines Agency website. [cited date]. Available from: https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu309653.
   Google Scholar
• Griffin M, Kelly R, Pike A. A review of the treatment landscape in paroxysmal nocturnal haemoglobinuria: where are we now and where are we going? Therapeutic Advances in Rare Disease. 2020;1:2633004020959349. doi:10.1177/2633004020959349.
   Google Scholar
• Hill A, Rother RP, Arnold L, et al. Eculizumab prevents intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and unmasks low-level extravascular hemolysis occurring through C3 opsonization. Haematologica. 2010 Apr;95(4):567–573. doi:10.3324/haematol.2009.007229.
   PubMed Web of Science ®Google Scholar
• Risitano AM. Paroxysmal nocturnal hemoglobinuria and the complement system: recent insights and novel anticomplement strategies. Adv Exp Med Biol. 2013;735:155–172. doi:10.1007/978-1-4614-4118-2_10.
   PubMed Web of Science ®Google Scholar
• Brodsky RA, Peffault de Latour R, Rottinghaus ST, et al. Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria. Haematologica. 2021 Jan;106(1):230–237. doi:10.3324/haematol.2019.236877.
   PubMed Web of Science ®Google Scholar
• Ravulizumab [package insert]. Boston, MA: Alexion Pharmaceuticals, Inc.; 2018. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761108s000lbl.pdf.
   Google Scholar
• Ravulizumab [package leaflet]. Boston, MA: Alexion Pharmaceuticals, Inc.; 2019. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/ultomiris.
   Google Scholar
• Risitano AM, Peffault de Latour R. How we(‘ll) treat paroxysmal nocturnal haemoglobinuria: diving into the future. Br J Haematol. 2022 Jan;196(2):288–303. doi:10.1111/bjh.17753.
   PubMed Web of Science ®Google Scholar
• Risitano AM, Notaro R, Marando L, et al. Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood. 2009 Apr;113(17):4094–4100. doi:10.1182/blood-2008-11-189944.
   PubMed Web of Science ®Google Scholar
• McKinley CE, Richards S, Munir T, et al. Extravascular hemolysis due to C3-loading in patients with PNH treated with eculizumab: defining the clinical syndrome. Blood. 2017;130:3471–3471.
   Web of Science ®Google Scholar
• Pegcetacoplan [package insert]. Waltham, MA: Apellis Pharmaceuticals, Inc.; 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215014s000lbl.pdf.
   Google Scholar
• Hillmen P, Szer J, Weitz I, et al. Pegcetacoplan versus eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2021 Mar;384(11):1028–1037. doi:10.1056/NEJMoa2029073.
   PubMed Web of Science ®Google Scholar
• Röth A HB, Griffin M, et al. Effect of pegcetacoplan on quality of life in patients with paroxysmal nocturnal hemoglobinuria from the Pegasus phase 3 trial comparing pegcetacoplan to eculizumab. Blood. 2020;136(Suppl. 1):10–12.
   Google Scholar
• Dingli D, Matos JE, Lehrhaupt K, et al. The burden of illness in patients with paroxysmal nocturnal hemoglobinuria receiving treatment with the C5-inhibitors eculizumab or ravulizumab: results from a US patient survey. Ann Hematol. 2022 Feb;101(2):251–263. doi:10.1007/s00277-021-04715-5.
   PubMed Web of Science ®Google Scholar
• Sharma A, Minh Duc NT, Luu Lam Thang T, et al. A consensus-based checklist for reporting of survey studies (CROSS). J Gen Intern Med. 2021 Oct;36(10):3179–3187. doi:10.1007/s11606-021-06737-1.
   PubMed Web of Science ®Google Scholar
• Badireddy M, Baradhi KM. Chronic anemia. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534803/.
   Google Scholar
• Cheng WY, Sarda SP, Mody-Patel N, et al. Real-world eculizumab dosing patterns among patients with paroxysmal nocturnal hemoglobinuria in a US population. Clinicoecon Outcomes Res. 2022;14:357–369. doi:10.2147/CEOR.S346816.
   PubMed Web of Science ®Google Scholar
• Kofahl C, Dierks M, Schulz-Nieswandt F. SelbstHILfe in Deutschland. Available from: https://www.nakos.de/data/Andere/2018/UKE-Broschuere-SHILD-Studie.pdf.
   Google Scholar
• PNH Support, UK. Data on file.
   Google Scholar
• Placeholder: chance data brief comparative regulatory frameworks.
   Google Scholar
• Schrezenmeier H, Kulasekararaj A, Mitchell L, et al. One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria naïve to complement inhibitor therapy: open-label extension of a randomized study. Ther Adv Hematol. 2020;11:2040620720966137. doi:10.1177/2040620720966137.
   Web of Science ®Google Scholar
• O’Connell TBM, Johnson S, Tu L, et al. Cost-utility analysis of ravulizumab compared with eculizumab in adult patients with paroxysmal nocturnal hemoglobinuria. Pharmacoeconomics. 2020;38(9):981–994.
   PubMed Web of Science ®Google Scholar
• Escalante CP, Chisolm S, Song J, et al. Fatigue, symptom burden, and health-related quality of life in patients with myelodysplastic syndrome, aplastic anemia, and paroxysmal nocturnal hemoglobinuria. Cancer Med. 2019 Feb;8(2):543–553. doi:10.1002/cam4.1953.
   PubMed Web of Science ®Google Scholar
• Panse J, de Fontbrune F S, Burmester P, et al. The burden of illness of patients with paroxysmal nocturnal haemoglobinuria receiving C5 inhibitors in France, Germany and the United Kingdom: patient-reported insights on symptoms and quality of life. Eur J Haematol. 2022 Jun. doi:10.1111/ejh.13816.
   Web of Science ®Google Scholar
• Montan I, Löwe B, Cella D, et al. General population norms for the functional assessment of chronic illness therapy (FACIT)-Fatigue scale. Value Health. 2018 Nov;21(11):1313–1321. doi:10.1016/j.jval.2018.03.013.
   PubMed Web of Science ®Google Scholar
• Cella D, Johansson P, Ueda Y, et al. Clinically important difference for the FACIT-Fatigue scale in paroxysmal nocturnal hemoglobinuria: a derivation from international PNH registry patient data. Blood. 2021;138(Supp. 1):1952.
   Google Scholar
• Hinz A, Singer S, Brähler E. European reference values for the quality of life questionnaire EORTC QLQ-C30: results of a German investigation and a summarizing analysis of six European general population normative studies. Acta Oncol. 2014 Jul;53(7):958–965. doi:10.3109/0284186x.2013.879998.
   PubMed Web of Science ®Google Scholar
• National Research C, Institute of M. The national academies collection: reports funded by national institutes of health. In: Woolf SH, Aron L, editors. US health in international perspective: shorter lives, poorer health. National Academies Press (US); 2013. PMID: 24006554.
   Google Scholar
• Kulasekararaj AG, Hill A, Rottinghaus ST, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019 Feb;133(6):540–549. doi:10.1182/blood-2018-09-876805.
   PubMed Web of Science ®Google Scholar
• Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019 Feb;133(6):530–539. doi:10.1182/blood-2018-09-876136.
   PubMed Web of Science ®Google Scholar
• Walentynowicz M, Schneider S, Stone AA. The effects of time frames on self-report. PLoS One. 2018;13(8):e0201655. doi:10.1371/journal.pone.0201655.
   PubMed Web of Science ®Google Scholar
• Althubaiti A. Information bias in health research: definition, pitfalls, and adjustment methods. J Multidiscip Healthc. 2016;9:211–217. doi:10.2147/jmdh.S104807.
   PubMed Web of Science ®Google Scholar
• Gerber GF, Yuan X, Yu J, et al. COVID-19 vaccines induce severe hemolysis in paroxysmal nocturnal hemoglobinuria. Blood. 2021 Jul;137(26):3670–3673. doi:10.1182/blood.2021011548.
   PubMed Web of Science ®Google Scholar
• Hines A, Hakim N, Barrientos J. COVID-19 infection presenting as paroxysmal nocturnal hemoglobinuria. Clin Case Rep. 2021 Aug;9(8):e04636. doi:10.1002/ccr3.4636.
   PubMed Web of Science ®Google Scholar
• Pike A, Muus P, Munir T, et al. COVID-19 infection in patients on anti-complement therapy: the Leeds national paroxysmal nocturnal haemoglobinuria service experience. Br J Haematol. 2020 Oct;191(1):e1–e4. doi:10.1111/bjh.17097.
   PubMed Web of Science ®Google Scholar
• Pravdic Z, Mitrovic M, Bogdanovic A, et al. COVID-19 presented with deep vein thrombosis in a patient with paroxysmal nocturnal haemoglobinuria. Hamostaseologie. 2021 Oct;41(5):397–399. doi:10.1055/a-1554-6432.
   PubMedGoogle Scholar
• Schüller H, Klein F, Lübbert M, et al. Hemolytic crisis in a patient treated with eculizumab for paroxysmal nocturnal hemoglobinuria possibly triggered by SARS-CoV-2 (COVID-19): a case report. Ann Hematol. 2021 Mar;100(3):841–842. doi:10.1007/s00277-020-04318-6.
   PubMed Web of Science ®Google Scholar