TY - JOUR
T1 - One-year outcomes from a phase 3 randomized trial of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria who received prior eculizumab
AU - Kulasekararaj, Austin G.
AU - Hill, Anita
AU - Langemeijer, Saskia
AU - Wells, Richard
AU - González Fernández, F. Ataúlfo
AU - Gaya, Anna
AU - Ojeda Gutierrez, Emilio
AU - Piatek, Caroline I.
AU - Mitchell, Lindsay
AU - Usuki, Kensuke
AU - Bosi, Alberto
AU - Brodsky, Robert A.
AU - Ogawa, Masayo
AU - Yu, Ji
AU - Ortiz, Stephan
AU - Röth, Alexander
AU - Lee, Jong Wook
AU - Peffault de Latour, Régis
N1 - Publisher Copyright:
© 2020 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd
PY - 2021/3
Y1 - 2021/3
N2 - Ravulizumab every 8 weeks showed non-inferiority to eculizumab every 2 weeks in a 26-week, phase 3, randomized controlled trial in adults with paroxysmal nocturnal hemoglobinuria (PNH) who were clinically stable on eculizumab (NCT03056040). We report results from the first 26 weeks of the extension period in which patients continued ravulizumab (n = 96) or switched from eculizumab to ravulizumab (n = 95). At week 52, mean (SD) lactate dehydrogenase levels increased 8.8% (29%) with ravulizumab-ravulizumab and 5.8% (27%) with eculizumab-ravulizumab from primary evaluation period baseline. During the extension period, four patients (ravulizumab-ravulizumab, n = 3; eculizumab-ravulizumab, n = 1) experienced breakthrough hemolysis, but none associated with serum free C5 ≥ 0.5 μg/mL. Mean Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores remained stable through week 52. During the extension period, proportions of patients avoiding transfusion remained stable (ravulizumab-ravulizumab, 86.5%; eculizumab-ravulizumab, 83.2%); 81.2% and 81.1%, respectively, had stabilized hemoglobin. All patients maintained serum free C5 levels < 0.5 μg/mL. Adverse events were generally similar between groups, and rates were lower in the extension period. Adults with PNH on stable eculizumab therapy who received ravulizumab over 52 weeks experienced durable efficacy, with consistent efficacy in patients who received eculizumab during the primary evaluation period and then switched to ravulizumab. Ravulizumab was well tolerated.
AB - Ravulizumab every 8 weeks showed non-inferiority to eculizumab every 2 weeks in a 26-week, phase 3, randomized controlled trial in adults with paroxysmal nocturnal hemoglobinuria (PNH) who were clinically stable on eculizumab (NCT03056040). We report results from the first 26 weeks of the extension period in which patients continued ravulizumab (n = 96) or switched from eculizumab to ravulizumab (n = 95). At week 52, mean (SD) lactate dehydrogenase levels increased 8.8% (29%) with ravulizumab-ravulizumab and 5.8% (27%) with eculizumab-ravulizumab from primary evaluation period baseline. During the extension period, four patients (ravulizumab-ravulizumab, n = 3; eculizumab-ravulizumab, n = 1) experienced breakthrough hemolysis, but none associated with serum free C5 ≥ 0.5 μg/mL. Mean Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores remained stable through week 52. During the extension period, proportions of patients avoiding transfusion remained stable (ravulizumab-ravulizumab, 86.5%; eculizumab-ravulizumab, 83.2%); 81.2% and 81.1%, respectively, had stabilized hemoglobin. All patients maintained serum free C5 levels < 0.5 μg/mL. Adverse events were generally similar between groups, and rates were lower in the extension period. Adults with PNH on stable eculizumab therapy who received ravulizumab over 52 weeks experienced durable efficacy, with consistent efficacy in patients who received eculizumab during the primary evaluation period and then switched to ravulizumab. Ravulizumab was well tolerated.
KW - breakthrough hemolysis
KW - complement inhibitor
KW - hemoglobin
KW - paroxysmal nocturnal hemoglobinuria
KW - quality of life
KW - transfusion
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U2 - 10.1111/ejh.13564
DO - 10.1111/ejh.13564
M3 - Article
C2 - 33301613
AN - SCOPUS:85099017694
SN - 0902-4441
VL - 106
SP - 389
EP - 397
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 3
ER -