Evaluation of Paroxysmal Nocturnal Hemoglobinuria Disease Burden: The Patient's Perspective. A Report From the International PNH Registry.
Authors: Muus Petra , Szer Jeffrey , Schrezenmeier Hubert , Brodsky Robert A , Bessler Monica , Socié Gérard , Urbano-Ispizua Alvaro , Maciejewski Jaroslaw P , Rosse Wendell F , Kanakura Yuzuru , Khursigara Gus , Karnell Anders , Bedrosian Camille L , Hillmen Peter 
Published: October 2019

Abstract 1525

Background:

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematopoietic stem cell disease characterized by complement-mediated hemolysis, a variable degree of bone marrow failure and thrombophilia, which may lead to reduced quality of life (QOL). There have been few reports of the disease burden of PNH from the patient's perspective.

Aims:

To describe patient-reported QOL, hospitalization, and missed work at time of PNH registry enrollment and to evaluate the association of these patient-reported outcomes (PROs) with demographics; patient reported symptoms (abdominal pain, chest pain and hemoglobinuria); and clinical characteristics (years since diagnosis, granulocyte clone size, underlying bone marrow disorder [BMD] and prior thrombotic event [TE]).

Methods:

Enrollment data from 117 clinical sites participating in the observational PNH Registry in 16 countries on 5 continents was analyzed. Patients are included in the Registry if they have a PNH clone regardless of clone size, other BMD, symptoms, or treatments. As part of the study, patients are asked to complete questionnaires at enrollment including the six subscales of the EORTC QLQ-C30 (range=0-100, higher scores better) and the FACIT-Fatigue scale (range=0-52, higher scores better). Patients are also asked “in the past 6 months have you been admitted to a hospital for your PNH” and “in the past 6 months did you miss work as a result of PNH” (questions about work were added later in the study). Statistical analysis used ANOVA and Chi-square tests as appropriate.

Results:

As of August 2010 there were 657 patients enrolled in the Registry. Of these, 377 (57%) patients completed a baseline questionnaire (BQ) and are included in this analysis. Patients with and without a completed BQ were comparable on most study variables, although patients with a higher clone size were less likely to complete a BQ. Patients had a mean age of 45.8±17.6 years; 54% were female. Median PNH (granulocyte) clone size was 75% (nearly two-thirds had a clone size ≥50%), 45% had BMD (mostly aplastic anemia) and 12% had history of TE. Abdominal pain in the last 6 months was reported by 45% of patients, chest pain by 28%, and hemoglobinuria by 64%. Mean EORTC scores (general population reference in parenthesis) were: global health=64.4 (71.2), physical functioning=79.7 (89.8), role functioning=73.9 (84.7), emotional functioning=76.0 (76.3), cognitive functioning=81.1 (86.1), and social functioning=77.2 (87.5). Thus, scores for PNH patients were decreased by about 10% in 4 of the 6 subscales. PNH patients had a mean FACIT-Fatigue score of 36.6, while a general population reference is 43.6 (or a 16% reduction). PROs were independent of time since diagnosis, PNH clone size, or underlying BMD. Males reported better physical, emotional, and social functioning and less fatigue than females (all p<.05). As expected, age strongly affected physical functioning (p<.01). Patients with prior TE reported worse global health, physical, role, cognitive functioning, and more fatigue than patients without prior TE (all p<.05). Patients reporting abdominal pain, chest pain, or hemoglobinuria had significantly worse EORTC and FACIT-fatigue scores on every scale (all p<.05). Overall, 26% of patients had a PNH-related hospitalization in the past 6 months. Patients who reported TE, abdominal pain, chest pain, or hemoglobinuria were more likely to be admitted to the hospital (all p<.05). There were 109 patients out of 244 (45%) who worked at a paid job. Of these,30% missed work in the past 6 months due to PNH. Patients were more likely to miss work if they had abdominal pain (47% vs 19%, p<.01 or hemoglobinuria (42% vs. 7%, p<.01).

Conclusion:

The disease burden to PNH patients is evident. Mean QOL is reduced in patients with PNH by 10 to 16% on most scales compared to the general population. One of four patients was hospitalized and 30% of patients with a paid job missed work due to PNH over a 6-month period. History of thrombosis and presence of PNH-related symptoms strongly affected QOL and hospitalization, while missed work was mostly impacted by symptoms. This global PNH Registry, which remains open to accrual (pnhregistry@iconplc.com), should help to redefine prospectively the long-term natural history of PNH, its treatments, and the outcomes of treatment, including outcomes measured from the patient's perspective.

Disclosures:

Muus: Celgene: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Szer:Alexion Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Schrezenmeier:Alexion Pharmaceuticals, Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees. Brodsky:Alexion Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees. Bessler:Alexion Pharmaceutical Inc: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Taligen: Consultancy. Socié:Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees. Urbano-Ispizua:Alexion: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Celgene: Research Funding; Eisai: Research Funding; Alexion: Consultancy. Rosse:Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kanakura:Alexion: Membership on an entity's Board of Directors or advisory committees. Khursigara:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Karnell:Alexion Pharma International: Employment, Equity Ownership. Bedrosian:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Hillmen:Alexion Pharmaceuticals, Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.