{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:57:59Z","timestamp":1789192679009,"version":"build-2803163510"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract\n<\/jats:title><jats:p>Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening disease with symptoms of hemolysis and thrombosis. Current therapies for this complement-mediated disease rely predominantly on inhibition of the C5 complement protein. However, data on treatment responses and quality of life in C5-inhibitor (C5i)-treated PNH patients are scarce. The objective of this study was to determine C5i treatment effects on clinical parameters, PNH symptoms, quality of life, and resource use for PNH patients. This cross-sectional study surveyed 122 individuals in the USA receiving treatment for PNH with C5-targeted monoclonal antibodies, eculizumab (ECU) or ravulizumab (RAV). Despite most patients receiving C5i therapy for\u2009\u2265\u20093\u00a0months (ECU 100%, <jats:italic>n<\/jats:italic>\u2009=\u200935; RAV 95.4%, <jats:italic>n<\/jats:italic>\u2009=\u200983), many patients remained anemic with hemoglobin levels\u2009\u2264\u200912\u00a0g\/dL in 87.5% (<jats:italic>n<\/jats:italic>\u2009=\u200928\/32) and 82.9% (<jats:italic>n<\/jats:italic>\u2009=\u200968\/82) of ECU and RAV recipients, respectively. A majority of patients on ECU (88.6%; <jats:italic>n<\/jats:italic>\u2009=\u200931\/35) and RAV (74.7%; <jats:italic>n<\/jats:italic>\u2009=\u200965\/87) reported fatigue symptoms. Among PNH patients receiving C5i therapy for\u2009\u2265\u200912\u00a0months, some still reported thrombotic events (ECU, 10.0%, <jats:italic>n<\/jats:italic>\u2009=\u20091\/10; RAV, 23.5%, <jats:italic>n<\/jats:italic>\u2009=\u20094\/17) and required transfusions within the past year (ECU, 52.2%, <jats:italic>n<\/jats:italic>\u2009=\u200912\/23; RAV, 22.6%, <jats:italic>n<\/jats:italic>\u2009=\u20097\/31). Other patient-reported PNH symptoms included breakthrough hemolysis, shortness of breath, and headaches. Patients reported scores below the average population norms on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scales. Overall, this study found that PNH patients receiving ECU or RAV therapy demonstrated a significant burden of illness, highlighting the need for improved PNH therapies.<\/jats:p>","DOI":"10.1007\/s00277-021-04715-5","type":"journal-article","created":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T07:16:29Z","timestamp":1641021389000},"page":"251-263","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["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"],"prefix":"10.1007","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7477-3004","authenticated-orcid":false,"given":"David","family":"Dingli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana E.","family":"Matos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerri","family":"Lehrhaupt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeeta","family":"Krishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Fishman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujata P.","family":"Sarda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott B.","family":"Baver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,1]]},"reference":[{"issue":"18","key":"4715_CR1","doi-asserted-by":"publisher","first-page":"2804","DOI":"10.1182\/blood-2014-02-522128","volume":"124","author":"RA Brodsky","year":"2014","unstructured":"Brodsky RA (2014) Paroxysmal nocturnal hemoglobinuria. Blood 124(18):2804\u20132811. https:\/\/doi.org\/10.1182\/blood-2014-02-522128","journal-title":"Blood"},{"issue":"4","key":"4715_CR2","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/0092-8674(93)90250-t","volume":"73","author":"J Takeda","year":"1993","unstructured":"Takeda J, Miyata T, Kawagoe K, Iida Y, Endo Y, Fujita T, Takahashi M, Kitani T, Kinoshita T (1993) Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell 73(4):703\u2013711. https:\/\/doi.org\/10.1016\/0092-8674(93)90250-t","journal-title":"Cell"},{"issue":"Jan 1","key":"4715_CR3","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1002\/j.1460-2075.1994.tb06240.x","volume":"13","author":"MMP Bessler","year":"1994","unstructured":"Bessler MMP, Hillmen P, Miyata T, Yamada N, Takeda J, Luzzatto L, Kinoshita T (1994) Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene. EMBO J 13(Jan 1):110\u2013117","journal-title":"EMBO J"},{"issue":"8","key":"4715_CR4","doi-asserted-by":"publisher","first-page":"587","DOI":"10.7326\/0003-4819-148-8-200804150-00003","volume":"148","author":"RA Brodsky","year":"2008","unstructured":"Brodsky RA (2008) Narrative review: Paroxysmal nocturnal hemoglobinuria: the physiology of complement-related hemolytic anemia. Ann Intern Med 148(8):587\u2013595. https:\/\/doi.org\/10.7326\/0003-4819-148-8-200804150-00003","journal-title":"Ann Intern Med"},{"key":"4715_CR5","unstructured":"de Latour RP, Risitano AM (2020) Hemolytic processes in paroxysmal nocturnal hemoglobinuria and its treatment: intravascular and extravascular hemolysis, introduction. In: Bone Marrow Transplantation. https:\/\/www.nature.com\/collections\/fichcejehg\/introduction. Accessed 5 Mar\u00a02021"},{"issue":"3","key":"4715_CR6","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1053\/j.seminhematol.2018.05.014","volume":"55","author":"R Notaro","year":"2018","unstructured":"Notaro R, Sica M (2018) C3-mediated extravascular hemolysis in PNH on eculizumab: mechanism and clinical implications. Semin Hematol 55(3):130\u2013135. https:\/\/doi.org\/10.1053\/j.seminhematol.2018.05.014","journal-title":"Semin Hematol"},{"issue":"5","key":"4715_CR7","doi-asserted-by":"publisher","first-page":"922","DOI":"10.3324\/haematol.2013.093161","volume":"99","author":"H Schrezenmeier","year":"2014","unstructured":"Schrezenmeier H, Muus P, Socie G, Szer J, Urbano-Ispizua A, Maciejewski JP, Brodsky RA, Bessler M, Kanakura Y, Rosse W, Khursigara G, Bedrosian C, Hillmen P (2014) Baseline characteristics and disease burden in patients in the international paroxysmal nocturnal hemoglobinuria registry. Haematologica 99(5):922\u2013929. https:\/\/doi.org\/10.3324\/haematol.2013.093161","journal-title":"Haematologica"},{"issue":"2","key":"4715_CR8","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1002\/cam4.1953","volume":"8","author":"CP Escalante","year":"2019","unstructured":"Escalante CP, Chisolm S, Song J, Richardson M, Salkeld E, Aoki E, Garcia-Manero G (2019) Fatigue, symptom burden, and health-related quality of life in patients with myelodysplastic syndrome, aplastic anemia, and paroxysmal nocturnal hemoglobinuria. Cancer Med 8(2):543\u2013553. https:\/\/doi.org\/10.1002\/cam4.1953","journal-title":"Cancer Med"},{"issue":"4","key":"4715_CR9","doi-asserted-by":"publisher","first-page":"e0195909","DOI":"10.1371\/journal.pone.0195909","volume":"13","author":"D Sheridan","year":"2018","unstructured":"Sheridan D, Yu ZX, Zhang Y, Patel R, Sun F, Lasaro MA, Bouchard K, Andrien B, Marozsan A, Wang Y, Tamburini P (2018) Design and preclinical characterization of ALXN1210: a novel anti-C5 antibody with extended duration of action. PLoS ONE 13(4):e0195909. https:\/\/doi.org\/10.1371\/journal.pone.0195909","journal-title":"PLoS ONE"},{"issue":"12","key":"4715_CR10","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1056\/NEJMoa061648","volume":"355","author":"P Hillmen","year":"2006","unstructured":"Hillmen P, Young NS, Schubert J, Brodsky RA, Socie G, Muus P, Roth A, Szer J, Elebute MO, Nakamura R, Browne P, Risitano AM, Hill A, Schrezenmeier H, Fu CL, Maciejewski J, Rollins SA, Mojcik CF, Rother RP, Luzzatto L (2006) The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med 355(12):1233\u20131243. https:\/\/doi.org\/10.1056\/NEJMoa061648","journal-title":"N Engl J Med"},{"issue":"4","key":"4715_CR11","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.1182\/blood-2007-06-094136","volume":"111","author":"RA Brodsky","year":"2008","unstructured":"Brodsky RA, Young NS, Antonioli E, Risitano AM, Schrezenmeier H, Schubert J, Gaya A, Coyle L, de Castro C, Fu CL, Maciejewski JP, Bessler M, Kroon HA, Rother RP, Hillmen P (2008) Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood 111(4):1840\u20131847. https:\/\/doi.org\/10.1182\/blood-2007-06-094136","journal-title":"Blood"},{"key":"4715_CR12","doi-asserted-by":"publisher","first-page":"204062072096613","DOI":"10.1177\/2040620720966137","volume":"11","author":"H Schrezenmeier","year":"2020","unstructured":"Schrezenmeier H, Kulasekararaj A, Mitchell L, Sicre de Fontbrune F, Devos T, Okamoto S, Wells R, Rottinghaus ST, Liu P, Ortiz S, Lee JW, Soci\u00e9 G (2020) One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria na\u00efve to complement inhibitor therapy: open-label extension of a randomized study. Ther Adv Hematol 11:2040620720966137. https:\/\/doi.org\/10.1177\/2040620720966137","journal-title":"Ther Adv Hematol"},{"issue":"Supplement 1","key":"4715_CR13","doi-asserted-by":"publisher","first-page":"3471","DOI":"10.1182\/blood.V130.Suppl_1.3471.3471","volume":"130","author":"CE McKinley","year":"2017","unstructured":"McKinley CE, Richards SJ, Munir T, Griffin M, Mitchell LD, Arnold L, Riley K, Copeland N, Newton DJ, Hill A, Hillmen P (2017) Extravascular hemolysis due to C3-loading in patients with PNH treated with eculizumab: defining the clinical syndrome. Blood 130(Supplement 1):3471\u20133471. https:\/\/doi.org\/10.1182\/blood.V130.Suppl_1.3471.3471","journal-title":"Blood"},{"issue":"4","key":"4715_CR14","doi-asserted-by":"publisher","first-page":"567","DOI":"10.3324\/haematol.2009.007229","volume":"95","author":"A Hill","year":"2010","unstructured":"Hill A, Rother RP, Arnold L, Kelly R, Cullen MJ, Richards SJ, Hillmen P (2010) Eculizumab prevents intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and unmasks low-level extravascular hemolysis occurring through C3 opsonization. Haematologica 95(4):567\u2013573. https:\/\/doi.org\/10.3324\/haematol.2009.007229","journal-title":"Haematologica"},{"issue":"1","key":"4715_CR15","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s13023-018-0810-x","volume":"13","author":"A Slade","year":"2018","unstructured":"Slade A, Isa F, Kyte D, Pankhurst T, Kerecuk L, Ferguson J, Lipkin G, Calvert M (2018) Patient reported outcome measures in rare diseases: a narrative review. Orphanet J Rare Dis 13(1):61. https:\/\/doi.org\/10.1186\/s13023-018-0810-x","journal-title":"Orphanet J Rare Dis"},{"key":"4715_CR16","doi-asserted-by":"publisher","DOI":"10.1007\/s40271-020-00493-w","author":"A Whittal","year":"2021","unstructured":"Whittal A, Meregaglia M, Nicod E (2021) The use of patient-reported outcome measures in rare diseases and implications for health technology assessment. Patient. https:\/\/doi.org\/10.1007\/s40271-020-00493-w","journal-title":"Patient"},{"key":"4715_CR17","doi-asserted-by":"publisher","unstructured":"Guidelines for good pharmacoepidemiology practice (GPP) (2016) Pharmacoepidemiology and drug safety 25 (1):2\u201310. https:\/\/doi.org\/10.1002\/pds.3891","DOI":"10.1002\/pds.3891"},{"key":"4715_CR18","doi-asserted-by":"publisher","unstructured":"Voigt P, von dem Bussche A (2017) Data protection regulation (GDPR) a practical guide. https:\/\/doi.org\/10.1007\/978-3-319-57959-7","DOI":"10.1007\/978-3-319-57959-7"},{"key":"4715_CR19","doi-asserted-by":"publisher","unstructured":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects (2013). Jama 310(20):2191\u20132194. https:\/\/doi.org\/10.1001\/jama.2013.281053","DOI":"10.1001\/jama.2013.281053"},{"key":"4715_CR20","unstructured":"Department of Health and Human Services, Office for Human Research Protections, and the Food and Drug Administration (2016) Use of electronic informed consent - questions and answers. Docket number FDA-2015-D-0390"},{"key":"4715_CR21","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1182\/blood.V108.11.985.985","volume":"108","author":"A Hill","year":"2006","unstructured":"Hill A, Platts P, Smith A, Richards S, Cullen M, Hill Q, Roman E, Hillmen P (2006) The incidence and prevalence of paroxysmal nocturnal hemoglobinuria (PNH) and survival of patients in Yorkshire. Blood 108:985\u2013985","journal-title":"Blood"},{"key":"4715_CR22","unstructured":"Rare Barometer (2018) Rare disease patients\u2019 participation in research. In: EURORDIS. http:\/\/download2.eurordis.org.s3.amazonaws.com\/rbv\/2018_02_12_rdd-research-survey-analysis.pdf. Accessed 23 Mar\u00a02021"},{"issue":"7","key":"4715_CR23","doi-asserted-by":"publisher","first-page":"958","DOI":"10.3109\/0284186X.2013.879998","volume":"53","author":"A Hinz","year":"2014","unstructured":"Hinz A, Singer S, Brahler E (2014) 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 53(7):958\u2013965. https:\/\/doi.org\/10.3109\/0284186X.2013.879998","journal-title":"Acta Oncol"},{"issue":"2","key":"4715_CR24","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1002\/cncr.10245","volume":"94","author":"D Cella","year":"2002","unstructured":"Cella D, Lai JS, Chang CH, Peterman A, Slavin M (2002) Fatigue in cancer patients compared with fatigue in the general United States population. Cancer 94(2):528\u2013538. https:\/\/doi.org\/10.1002\/cncr.10245","journal-title":"Cancer"},{"issue":"11","key":"4715_CR25","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1016\/j.jval.2018.03.013","volume":"21","author":"I Montan","year":"2018","unstructured":"Montan I, L\u00f6we B, Cella D, Mehnert A, Hinz A (2018) General population norms for the functional assessment of chronic illness therapy (FACIT)-fatigue scale. Value Health 21(11):1313\u20131321. https:\/\/doi.org\/10.1016\/j.jval.2018.03.013","journal-title":"Value Health"},{"key":"4715_CR26","volume-title":"EORTC QLQ-C30 reference values","author":"NW Scott","year":"2008","unstructured":"Scott NW, Fayers PM, Aaronson NK, Bottomley A, Graeff Ad, Groenvold M, Gundy C, Koller M, Petersen MA, Sprangers MA (2008) EORTC QLQ-C30 reference values. European Organisation for Research and Treatment of Cancer, Brussels"},{"issue":"3","key":"4715_CR27","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1111\/j.1445-5994.2012.02924.x","volume":"43","author":"I Weitz","year":"2013","unstructured":"Weitz I, Meyers G, Lamy T, Cahn JY, Uranga MT, Garc\u00eda Vela JA, Sanz MA, Severino B, Kelly RJ, Hillmen P, Hill A (2013) Cross-sectional validation study of patient-reported outcomes in patients with paroxysmal nocturnal haemoglobinuria. Intern Med J 43(3):298\u2013307. https:\/\/doi.org\/10.1111\/j.1445-5994.2012.02924.x","journal-title":"Intern Med J"},{"issue":"5","key":"4715_CR28","doi-asserted-by":"publisher","first-page":"353","DOI":"10.2165\/00019053-199304050-00006","volume":"4","author":"MC Reilly","year":"1993","unstructured":"Reilly MC, Zbrozek AS, Dukes EM (1993) The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics 4(5):353\u2013365. https:\/\/doi.org\/10.2165\/00019053-199304050-00006","journal-title":"Pharmacoeconomics"},{"issue":"1","key":"4715_CR29","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1037\/a0030932","volume":"18","author":"E Gosselin","year":"2013","unstructured":"Gosselin E, Lemyre L, Corneil W (2013) Presenteeism and absenteeism: differentiated understanding of related phenomena. J Occup Health Psychol 18(1):75\u201386. https:\/\/doi.org\/10.1037\/a0030932","journal-title":"J Occup Health Psychol"},{"key":"4715_CR30","unstructured":"US Food and Drug Administration (2007) Alexion Pharmaceuticals, Inc. Soliris (eculizumab) [package insert]. Reference ID 4171013"},{"key":"4715_CR31","unstructured":"US Food and Drug Administration (2018) Alexion Pharmaceuticals, Inc. Ultomiris (ravulizumab-cwvz) [package insert]. Reference ID 4367173"},{"issue":"7","key":"4715_CR32","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1007\/s00277-020-04052-z","volume":"99","author":"H Schrezenmeier","year":"2020","unstructured":"Schrezenmeier H, Roth A, Araten DJ, Kanakura Y, Larratt L, Shammo JM, Wilson A, Shayan G, Maciejewski JP (2020) Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry. Ann Hematol 99(7):1505\u20131514. https:\/\/doi.org\/10.1007\/s00277-020-04052-z","journal-title":"Ann Hematol"},{"issue":"25","key":"4715_CR33","doi-asserted-by":"publisher","first-page":"6786","DOI":"10.1182\/blood-2011-02-333997","volume":"117","author":"RJ Kelly","year":"2011","unstructured":"Kelly RJ, Hill A, Arnold LM, Brooksbank GL, Richards SJ, Cullen M, Mitchell LD, Cohen DR, Gregory WM, Hillmen P (2011) Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood 117(25):6786\u20136792. https:\/\/doi.org\/10.1182\/blood-2011-02-333997","journal-title":"Blood"},{"issue":"4","key":"4715_CR34","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1002\/ajh.24278","volume":"91","author":"M Loschi","year":"2016","unstructured":"Loschi M, Porcher R, Barraco F, Terriou L, Mohty M, de Guibert S, Mahe B, Lemal R, Dumas PY, Etienne G, Jardin F, Royer B, Bordessoule D, Rohrlich PS, Fornecker LM, Salanoubat C, Maury S, Cahn JY, Vincent L, Sene T, Rigaudeau S, Nguyen S, Lepretre AC, Mary JY, Corront B, Socie G, Peffault de Latour R (2016) Impact of eculizumab treatment on paroxysmal nocturnal hemoglobinuria: a treatment versus no-treatment study. Am J Hematol 91(4):366\u2013370. https:\/\/doi.org\/10.1002\/ajh.24278","journal-title":"Am J Hematol"},{"issue":"Supplement 1","key":"4715_CR35","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1182\/blood-2020-141636","volume":"136","author":"WY Cheng","year":"2020","unstructured":"Cheng WY, Sarda SP, Mody-Patel N, Krishnan S, Yenikomshian M, Scoble PJ, Kunzweiler C, Vu JD, Cheung HC, Duh MS (2020) Real-world eculizumab dosing patterns among patients with paroxysmal nocturnal hemoglobinuria in a US population. Blood 136(Supplement 1):13\u201313. https:\/\/doi.org\/10.1182\/blood-2020-141636","journal-title":"Blood"},{"key":"4715_CR36","unstructured":"WHO Scientific Group on Nutritional Anaemias & World Health Organization (1968) Nutritional anaemias: report of a WHO scientific group [\u200emeeting held in Geneva from 13 to 17 March 1967].\u00a0World Health Organization. In: World Health Organization. https:\/\/apps.who.int\/iris\/handle\/10665\/40707. Accessed 5 Mar\u00a02021"},{"key":"4715_CR37","doi-asserted-by":"publisher","first-page":"109","DOI":"10.2147\/VHRM.S140951","volume":"14","author":"M Stucchi","year":"2018","unstructured":"Stucchi M, Cantoni S, Piccinelli E, Savonitto S, Morici N (2018) Anemia and acute coronary syndrome: current perspectives. Vasc Health Risk Manag 14:109\u2013118. https:\/\/doi.org\/10.2147\/VHRM.S140951","journal-title":"Vasc Health Risk Manag"},{"key":"4715_CR38","unstructured":"Brodsky R (2019) Paroxysmal nocturnal hemoglobinuria. In: Rheumatology Advisor. https:\/\/www.rheumatologyadvisor.com\/home\/decision-support-in-medicine\/hematology\/paroxysmal-nocturnal-hemoglobinuria-2\/. Accessed 23 Mar\u00a02021"},{"issue":"6","key":"4715_CR39","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1007\/s12185-018-2409-3","volume":"107","author":"Y Ueda","year":"2018","unstructured":"Ueda Y, Obara N, Yonemura Y, Noji H, Masuko M, Seki Y, Wada K, Matsuda T, Akiyama H, Ikezoe T, Chiba S, Kanda Y, Kawaguchi T, Shichishima T, Nakakuma H, Okamoto S, Nishimura J-i, Kanakura Y, Ninomiya H (2018) Effects of eculizumab treatment on quality of life in patients with paroxysmal nocturnal hemoglobinuria in Japan. Int J Hematol 107(6):656\u2013665. https:\/\/doi.org\/10.1007\/s12185-018-2409-3","journal-title":"Int J Hematol"},{"issue":"12-b Suppl","key":"4715_CR40","doi-asserted-by":"publisher","first-page":"S8","DOI":"10.18553\/jmcp.2020.26.12-b.s8","volume":"26","author":"M Bektas","year":"2020","unstructured":"Bektas M, Copley-Merriman C, Khan S, Sarda SP, Shammo JM (2020) Paroxysmal nocturnal hemoglobinuria: patient journey and burden of disease. J Manag Care Spec Pharm 26(12-b Suppl):S8\u2013S14. https:\/\/doi.org\/10.18553\/jmcp.2020.26.12-b.s8","journal-title":"J Manag Care Spec Pharm"},{"issue":"6","key":"4715_CR41","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/s0885-3924(02)00529-8","volume":"24","author":"D Cella","year":"2002","unstructured":"Cella D, Eton DT, Lai JS, Peterman AH, Merkel DE (2002) Combining anchor and distribution-based methods to derive minimal clinically important differences on the functional assessment of cancer therapy (FACT) anemia and fatigue scales. J Pain Symptom Manage 24(6):547\u2013561. https:\/\/doi.org\/10.1016\/s0885-3924(02)00529-8","journal-title":"J Pain Symptom Manage"},{"issue":"1","key":"4715_CR42","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1200\/jco.1998.16.1.139","volume":"16","author":"D Osoba","year":"1998","unstructured":"Osoba D, Rodrigues G, Myles J, Zee B, Pater J (1998) Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol 16(1):139\u2013144. https:\/\/doi.org\/10.1200\/jco.1998.16.1.139","journal-title":"J Clin Oncol"},{"issue":"6","key":"4715_CR43","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1007\/bf00439229","volume":"5","author":"MT King","year":"1996","unstructured":"King MT (1996) The interpretation of scores from the EORTC quality of life questionnaire QLQ-C30. Qual Life Res 5(6):555\u2013567. https:\/\/doi.org\/10.1007\/bf00439229","journal-title":"Qual Life Res"},{"issue":"13","key":"4715_CR44","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1016\/j.ejca.2008.05.008","volume":"44","author":"K Cocks","year":"2008","unstructured":"Cocks K, King MT, Velikova G, Fayers PM, Brown JM (2008) Quality, interpretation and presentation of European organisation for research and treatment of cancer quality of life questionnaire core 30 data in randomised controlled trials. Eur J Cancer 44(13):1793\u20131798. https:\/\/doi.org\/10.1016\/j.ejca.2008.05.008","journal-title":"Eur J Cancer"},{"issue":"9","key":"4715_CR45","doi-asserted-by":"publisher","first-page":"2107","DOI":"10.1093\/annonc\/mdq726","volume":"22","author":"J Maringwa","year":"2011","unstructured":"Maringwa J, Quinten C, King M, Ringash J, Osoba D, Coens C, Martinelli F, Reeve BB, Gotay C, Greimel E, Flechtner H, Cleeland CS, Schmucker-Von Koch J, Weis J, Van Den Bent MJ, Stupp R, Taphoorn MJ, Bottomley A (2011) Minimal clinically meaningful differences for the EORTC QLQ-C30 and EORTC QLQ-BN20 scales in brain cancer patients. Ann Oncol 22(9):2107\u20132112. https:\/\/doi.org\/10.1093\/annonc\/mdq726","journal-title":"Ann Oncol"},{"key":"4715_CR46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/2633004020959349","volume":"1","author":"M Griffin","year":"2020","unstructured":"Griffin M, Kelly R, Pike A (2020) A review of the treatment landscape in paroxysmal nocturnal haemoglobinuria: where are we now and where are we going? Ther Adv Rare Dis 1:1\u201312. https:\/\/doi.org\/10.1177\/2633004020959349","journal-title":"Ther Adv Rare Dis"},{"key":"4715_CR47","unstructured":"US Food and Drug Administration (2021) Apellis Pharmaceuticals, Inc. Empaveli (pegcetacoplan) [package insert]. Reference ID 4796130"},{"issue":"11","key":"4715_CR48","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1056\/NEJMoa2029073","volume":"384","author":"P Hillmen","year":"2021","unstructured":"Hillmen P, Szer J, Weitz I, R\u00f6th A, H\u00f6chsmann B, Panse J, Usuki K, Griffin M, Kiladjian J-J, de Castro C, Nishimori H, Tan L, Hamdani M, Deschatelets P, Francois C, Grossi F, Ajayi T, Risitano A, de la Tour RP (2021) Pegcetacoplan versus eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med 384(11):1028\u20131037. https:\/\/doi.org\/10.1056\/NEJMoa2029073","journal-title":"N Engl J Med"},{"issue":"Supplement 1","key":"4715_CR49","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1182\/blood-2020-134581","volume":"136","author":"A R\u00f6th","year":"2020","unstructured":"R\u00f6th A, Hoechsmann B, Griffin M, de Castro CM, Szer J, Usuki K, Soret J, Hamdani M, Ajayi T, Sarda SP, Panse J (2020) Effect of pegcetacoplan on quality of life in patients with paroxysmal nocturnal hemoglobinuria from the Pegasus phase 3 trial comparing pegcetacoplan to eculizumab. Blood 136(Supplement 1):10\u201312. https:\/\/doi.org\/10.1182\/blood-2020-134581","journal-title":"Blood"},{"issue":"8","key":"4715_CR50","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1097\/mlr.0000000000000753","volume":"55","author":"P St Clair","year":"2017","unstructured":"St Clair P, Gaudette \u00c9, Zhao H, Tysinger B, Seyedin R, Goldman DP (2017) Using self-reports or claims to assess disease prevalence: it\u2019s complicated. Med Care 55(8):782\u2013788. https:\/\/doi.org\/10.1097\/mlr.0000000000000753","journal-title":"Med Care"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-021-04715-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-021-04715-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-021-04715-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T09:04:09Z","timestamp":1641632649000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-021-04715-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,1]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["4715"],"URL":"https:\/\/doi.org\/10.1007\/s00277-021-04715-5","relation":{},"ISSN":["0939-5555","1432-0584"],"issn-type":[{"value":"0939-5555","type":"print"},{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,1]]},"assertion":[{"value":"10 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"A study exemption from US Central Institutional Review Board (IRB) was obtained before the initiation of the survey. This study was in a category of exempt human studies research as it utilized survey procedures to gather data.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"In accordance with the Declaration of Helsinki ethical principles for medical research and the US Office of Human Research Protections guidance about informed consent, all participants electronically provided documentation of their informed consent as evidence of their agreement to voluntarily participate in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"DD is a consultant\/advisory board member for Apellis Pharmaceuticals, Inc., Alexion, Janssen, Millennium\/Takeda, Novartis, R-Pharm, Rigel, and Sanofi, and recipient of research grants from Juno, and Karyopharm. JEM and KL are current employees at Kantar Health. SK, MY, JF, SPS, and SBB are current employees and equity holders of Apellis Pharmaceuticals, Inc.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}