TY - JOUR
T1 - Clinical benefit of eculizumab in patients with no transfusion history in the International Paroxysmal Nocturnal Haemoglobinuria Registry
AU - Almeida, António M.
AU - Bedrosian, Camille
AU - Cole, Alexander
AU - Muus, Petra
AU - Schrezenmeier, Hubert
AU - Szer, Jeff
AU - Rosse, Wendell F.
N1 - Funding Information:
Funding: Logistical and financial support for the PNH Registry was provided by Alexion Pharmaceuticals. Conflict of interest: P. Muss has received speaker fees from Alexion Pharmaceuticals. J. Szer received lecture fees from Alexion. A. M. Almeida has received speaker fees from Alexion Pharmaceuticals. The institution of H. Schrezenmeier has received research grants from Alexion Pharmaceuticals and H. Schrezenmeier has received payment from Alexion Pharmaceuticals and Ra Pharma as an advisory board member and payment from Alexion Pharmaceuticals as symposia speaker.
Publisher Copyright:
© 2017 Royal Australasian College of Physicians
PY - 2017/9
Y1 - 2017/9
N2 - Background: Eculizumab reduces intravascular haemolysis and improves disease symptoms in patients with paroxysmal nocturnal haemoglobinuria (PNH). Aims: To characterise, in a real-world setting, the effect of eculizumab in patients with haemolytic PNH (lactase dehydrogenase (LDH) ≥ 1.5 upper limit of normal) and no history of red blood cell transfusion, including those with high disease activity (HDA). Methods: Three populations from the International PNH Registry were studied: (i) non-transfused, untreated; (ii) non-transfused, eculizumab-treated and (iii) transfused, eculizumab-treated (≥1 transfusions in 6 months prior to eculizumab initiation). Using multivariate linear regression, the primary outcome was mean absolute change from baseline to 6 months in LDH (U/L) in non-transfused patients who were treated with eculizumab versus those who remained untreated. Secondary outcomes were mean changes in functional assessment of chronic illness therapy (FACIT)-Fatigue and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30 Fatigue scores from baseline to last available assessment. Results: The study population included (i) 144 non-transfused, untreated patients; (ii) 45 non-transfused, eculizumab-treated patients and (iii) 105 transfused, eculizumab-treated patients. Of these, 136/144, 43/45 and 99/105 had HDA respectively. Compared with untreated patients, non-transfused, treated patients had greater absolute reduction in LDH (−1318.8 vs −39.4; P < 0.001) and greater percentage reduction in LDH (−69.9 vs −1.6%; P < 0.001). Clinically meaningful improvements in FACIT-Fatigue (73.7 vs 24.6%, respectively) and in EORTC-QLQ-C30 (84.2 vs 33.3%, respectively) were observed. Non-transfused, treated patients with HDA had significantly reduced LDH levels (P < 0.001) and clinically meaningful improvements in FACIT-Fatigue (P = 0.003) and EORTC-QLQ-C30 (P = 0.020) versus untreated patients. Conclusion: Significant LDH reduction and clinically meaningful improvement in fatigue were observed in patients with PNH and HDA treated with eculizumab versus untreated patients, irrespective of transfusion history.
AB - Background: Eculizumab reduces intravascular haemolysis and improves disease symptoms in patients with paroxysmal nocturnal haemoglobinuria (PNH). Aims: To characterise, in a real-world setting, the effect of eculizumab in patients with haemolytic PNH (lactase dehydrogenase (LDH) ≥ 1.5 upper limit of normal) and no history of red blood cell transfusion, including those with high disease activity (HDA). Methods: Three populations from the International PNH Registry were studied: (i) non-transfused, untreated; (ii) non-transfused, eculizumab-treated and (iii) transfused, eculizumab-treated (≥1 transfusions in 6 months prior to eculizumab initiation). Using multivariate linear regression, the primary outcome was mean absolute change from baseline to 6 months in LDH (U/L) in non-transfused patients who were treated with eculizumab versus those who remained untreated. Secondary outcomes were mean changes in functional assessment of chronic illness therapy (FACIT)-Fatigue and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30 Fatigue scores from baseline to last available assessment. Results: The study population included (i) 144 non-transfused, untreated patients; (ii) 45 non-transfused, eculizumab-treated patients and (iii) 105 transfused, eculizumab-treated patients. Of these, 136/144, 43/45 and 99/105 had HDA respectively. Compared with untreated patients, non-transfused, treated patients had greater absolute reduction in LDH (−1318.8 vs −39.4; P < 0.001) and greater percentage reduction in LDH (−69.9 vs −1.6%; P < 0.001). Clinically meaningful improvements in FACIT-Fatigue (73.7 vs 24.6%, respectively) and in EORTC-QLQ-C30 (84.2 vs 33.3%, respectively) were observed. Non-transfused, treated patients with HDA had significantly reduced LDH levels (P < 0.001) and clinically meaningful improvements in FACIT-Fatigue (P = 0.003) and EORTC-QLQ-C30 (P = 0.020) versus untreated patients. Conclusion: Significant LDH reduction and clinically meaningful improvement in fatigue were observed in patients with PNH and HDA treated with eculizumab versus untreated patients, irrespective of transfusion history.
KW - Eculizumab
KW - High disease activity
KW - Outcome
KW - Paroxysmal nocturnal haemoglobinuria
KW - Transfusion
UR - http://www.scopus.com/inward/record.url?scp=85029028390&partnerID=8YFLogxK
U2 - 10.1111/imj.13523
DO - 10.1111/imj.13523
M3 - Article
C2 - 28608499
AN - SCOPUS:85029028390
SN - 1444-0903
VL - 47
SP - 1026
EP - 1034
JO - Internal Medicine Journal
JF - Internal Medicine Journal
IS - 9
ER -