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ORIGINAL RESEARCH

Low Rate of Clinically Evident Extravascular Hemolysis in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with a Complement C5 Inhibitor: Results from a Large, Multicenter, US Real-World Study

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Pages 425-437 | Received 22 Feb 2022, Accepted 29 Jun 2022, Published online: 12 Aug 2022

References

  • Takeda J, Miyata T, Kawagoe K, et al. Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell. 1993;73(4):703–711. doi:10.1016/0092-8674(93)90250-t
  • Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804–2811. doi:10.1182/blood-2014-02-522128
  • Hillmen P, Bessler M, Mason PJ, Watkins WM, Luzzatto L. Specific defect in N-acetylglucosamine incorporation in the biosynthesis of the glycosylphosphatidylinositol anchor in cloned cell lines from patients with paroxysmal nocturnal hemoglobinuria. Proc Natl Acad Sci USA. 1993;90(11):5272–5276. doi:10.1073/pnas.90.11.5272
  • Hillmen P, Hows JM, Luzzatto L. Two distinct patterns of glycosylphosphatidylinositol (GPI) linked protein deficiency in the red cells of patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 1992;80(3):399–405. doi:10.1111/j.1365-2141.1992.tb08151.x
  • Holguin MH, Fredrick LR, Bernshaw NJ, Wilcox LA, Parker CJ. Isolation and characterization of a membrane protein from normal human erythrocytes that inhibits reactive lysis of the erythrocytes of paroxysmal nocturnal hemoglobinuria. J Clin Invest. 1989;84(1):7–17. doi:10.1172/JCI114172
  • Moyo VM, Mukhina GL, Garrett ES, Brodsky RA. Natural history of paroxysmal nocturnal haemoglobinuria using modern diagnostic assays. Br J Haematol. 2004;126(1):133–138. doi:10.1111/j.1365-2141.2004.04992.x
  • Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA. 2005;293(13):1653–1662. doi:10.1001/jama.293.13.1653
  • SOLIRIS® (Eculizumab) Injection, for Intravenous Use. Alexion Pharmaceuticals, Boston MA. 11/2020.
  • ULTOMIRIS® (Ravulizumab-cwvz) Injection, for Intravenous Use. Alexion Pharmaceuticals, Boston MA. 10/2019.
  • Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355(12):1233–1243. doi:10.1056/NEJMoa061648
  • 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;350(6):552–559. doi:10.1056/NEJMoa031688
  • Hillmen P, Muus P, Duhrsen U, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007;110(12):4123–4128. doi:10.1182/blood-2007-06-095646
  • Hill A, Rother RP, Wang X, et al. Effect of eculizumab on haemolysis-associated nitric oxide depletion, dyspnoea, and measures of pulmonary hypertension in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2010;149(3):414–425. doi:10.1111/j.1365-2141.2010.08096.x
  • Hillmen P, Elebute M, Kelly R, et al. Long-term effect of the complement inhibitor eculizumab on kidney function in patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2010;85(8):553–559. doi:10.1002/ajh.21757
  • Hillmen P, Muus P, Roth A, et al. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2013;162(1):62–73. doi:10.1111/bjh.12347
  • Brodsky RA, Young NS, Antonioli E, et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008;111(4):1840–1847. doi:10.1182/blood-2007-06-094136
  • Ninomiya H, Obara N, Chiba S, et al. Interim analysis of post-marketing surveillance of eculizumab for paroxysmal nocturnal hemoglobinuria in Japan. Int J Hematol. 2016;104(5):548–558. doi:10.1007/s12185-016-2065-4
  • Loschi M, Porcher R, Barraco F, et al. Impact of eculizumab treatment on paroxysmal nocturnal hemoglobinuria: a treatment versus no-treatment study. Am J Hematol. 2016;91(4):366–370. doi:10.1002/ajh.24278
  • 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;133(6):530–539. doi:10.1182/blood-2018-09-876136
  • 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;133(6):540–549. doi:10.1182/blood-2018-09-876805
  • Schrezenmeier H, Kulasekararaj A, Mitchell L, et al. One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria naive to complement inhibitor therapy: open-label extension of a randomized study. Ther Adv Hematol. 2020;11:2040620720966137. doi:10.1177/2040620720966137
  • Kulasekararaj AG, Hill A, Langemeijer S, et al. One-year outcomes from a phase 3 randomized trial of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria who received prior eculizumab. Eur J Haematol. 2021;106(3):389–397. doi:10.1111/ejh.13564
  • Brodsky RA, de Latour R Peffault, ST Rottinghaus, 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;106(1):230–237. doi:10.3324/haematol.2019.236877
  • 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;95(4):567–573. doi:10.3324/haematol.2009.007229
  • 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;113(17):4094–4100. doi:10.1182/blood-2008-11-189944
  • Subias Hidalgo M, Martin Merinero H, Lopez A, et al. Extravascular hemolysis and complement consumption in paroxysmal nocturnal hemoglobinuria patients undergoing eculizumab treatment. Immunobiology. 2017;222(2):363–371. doi:10.1016/j.imbio.2016.09.002
  • Kulasekararaj AG, Brodsky RA, Hill A. Monitoring of patients with paroxysmal nocturnal hemoglobinuria on a complement inhibitor. Am J Hematol. 2021;96(7):E232–E235. doi:10.1002/ajh.26176
  • Debureaux PE, Kulasekararaj AG, Cacace F, et al. Categorizing hematological response to eculizumab in paroxysmal nocturnal hemoglobinuria: a multicenter real-life study. Bone Marrow Transplant. 2021;56(10):2600–2602. doi:10.1038/s41409-021-01372-0
  • Risitano AM, Notaro R, Luzzatto L, Hill A, Kelly R, Hillmen P. Paroxysmal nocturnal hemoglobinuria–hemolysis before and after eculizumab. N Engl J Med. 2010;363(23):2270–2272. doi:10.1056/NEJMc1010351
  • Patriquin CJ, Kiss T, Caplan S, et al. How we treat paroxysmal nocturnal hemoglobinuria: a consensus statement of the Canadian PNH Network and review of the national registry. Eur J Haematol. 2019;102(1):36–52. doi:10.1111/ejh.13176
  • Dezern AE, Borowitz MJ. ICCS/ESCCA consensus guidelines to detect GPI-deficient cells in paroxysmal nocturnal hemoglobinuria (PNH) and related disorders part 1 - clinical utility. Cytometry B Clin Cytom. 2018;94(1):16–22. doi:10.1002/cyto.b.21608
  • Killick SB, Bown N, Cavenagh J, et al. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016;172(2):187–207. doi:10.1111/bjh.13853
  • Schubert J, Röth A, Bettelheim P, et al. Paroxysmale nächtliche Hämoglobinurie (PNH). Available from: https://www.onkopedia.com/de/onkopedia/guidelines/paroxysmale-naechtliche-haemoglobinurie-pnh/@@guideline/html/index.html. Accessed July 21, 2021.
  • ClinicalTrials.gov. Danicopan as add-on therapy to a C5 inhibitor in paroxysmal nocturnal hemoglobinuria (PNH) participants who have clinically evident extravascular hemolysis (EVH)(ALPHA). Available from: https://clinicaltrials.gov/ct2/show/NCT04469465?term=danicopan&draw=2&rank=5. Accessed May 20, 2021.
  • Sica M, Rondelli T, Ricci P, De Angioletti M, Risitano AM, Notaro R. Eculizumab treatment: stochastic occurrence of C3 binding to individual PNH erythrocytes. J Hematol Oncol. 2017;10(1):126. doi:10.1186/s13045-017-0496-x
  • Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333(19):1253–1258. doi:10.1056/NEJM199511093331904
  • Kelly RJ, Hill A, Arnold LM, et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood. 2011;117(25):6786–6792. doi:10.1182/blood-2011-02-333997
  • Hillmen P, Szer J, Weitz I, et al. Pegcetacoplan versus eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2021;384(11):1028–1037. doi:10.1056/NEJMoa2029073
  • Gurnari C, Pagliuca S, Maciejewski JP. Pegcetacoplan versus eculizumab in PNH. N Engl J Med. 2021;385(18):1725. doi:10.1056/NEJMc2106424
  • Kulasekararaj AG, Gandhi S, Brodsky RA. Pegcetacoplan versus eculizumab in PNH. N Engl J Med. 2021;385(18):1724–1725. doi:10.1056/NEJMc2106424
  • Ueda Y, Takamori H, Nishimura JI. Pegcetacoplan versus eculizumab in PNH. N Engl J Med. 2021;385(18):1723–1724. doi:10.1056/NEJMc2106424
  • Schrezenmeier H, Roth 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;99(7):1505–1514. doi:10.1007/s00277-020-04052-z
  • Nakayama H, Usuki K, Echizen H, Ogawa R, Orii T. Eculizumab dosing intervals longer than 17 days may be associated with greater risk of breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria. Biol Pharm Bull. 2016;39(2):285–288. doi:10.1248/bpb.b15-00703
  • Peffault de Latour R, Fremeaux-Bacchi V, Porcher R, et al. Assessing complement blockade in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab. Blood. 2015;125(5):775–783. doi:10.1182/blood-2014-03-560540
  • Griffin M, Kulasekararaj A, Gandhi S, et al. Concurrent treatment of aplastic anemia/paroxysmal nocturnal hemoglobinuria syndrome with immunosuppressive therapy and eculizumab: a UK experience. Haematologica. 2018;103(8):e345–e347. doi:10.3324/haematol.2017.183046