The global PNH patient registry:  real-world data on PNH symptom burden and quality of life

Abstract

Abstract Introduction: Current knowledge of the lived experience of individuals with Paroxysmal Nocturnal Hemoglobinuria (PNH) is informed by data collected during clinical trials. This information is therefore short-term and limited to individuals who choose to participate in an interventional trial. The Global PNH Patient Registry, sponsored by the Aplastic Anemia and MDS International Foundation, was designed to understand the impact of care and treatment effectiveness in real-world settings. It is the first patient-driven and patient-focused PNH registry with all data provided by individuals living with PNH or their caregivers. We explored the longitudinal symptom burden and measures of quality of life (QoL) to quantify the impact of a diagnosis of PNH in this population living during this era of available complement inhibitor medications. Methods: Individuals with a self-reported PNH diagnosis are eligible to participate. The Global PNH Patient Registry is hosted on the National Organization for Rare Disorders' IAMRARE® platform – a web-based, secure portal for obtaining consent and entering patient-reported data. Study participants need to be able to read English or Spanish and have access to the internet. The study was reviewed and approved by North Star Review Board (IRB #NB100005). Participants were asked to report their frequency of experience with 26 symptoms, rated on a 5-point Likert scale. In addition, PROMIS measures for seven QoL domains are included. After initial survey completion, participants are notified every 6 months to update information. Longitudinal data was examined by calendar year of submission for all participants and within participants among those with longitudinal data. This analysis includes data provided between the registry launch in April 2021 and December 31, 2024. Results: The symptom survey and the two QoL surveys were initially completed by 171, 160 and 154 participants, respectively, with 61, 56 and 57 participants completing at least one longitudinal survey. The demographics of the study population were: 38% aged 50 or older, 64% female, 67% Non-Hispanic, White, 68% resided in the United States, 38% with a diagnosis of aplastic anemia, and 68% reported ever taking a complement inhibitor medication. At their initial survey submission, 67% of participants reported experiencing 10 or more symptoms and 20% reported experiencing 10 or more symptoms always or almost always. Among the QoL domains, 66% reported scores that indicated impairment for 3 or more of the domains. The percentage of participants reporting experiencing 10 or more symptoms decreased from 2021 to 2024 (76%, 66%, 64% and 56%, respectively). The percentages for experiencing 10 or more symptoms almost always or always were 12%, 19%, 16% and 11%. For the QoL scores the percentage with scores indicating impairment for 3 or more domains from 2021 – 2024 were: 70%, 62%, 72% and 58%. Among individuals with multiple submissions, the direction of change was investigated. Across all symptoms, between 3% and 18% changed from reporting a symptom to not reporting it and between 3% and 17% of participants changed from initially not reporting the symptom to reporting it. For the QoL domains, between 0% to 12% changed from an initial score indicating impairment to a score in the normal range and between 4% to 16% changed from an initial score indicating impairment to a score in the normal range. However, 98% of participants had physical function scores indicating impairment and there were no participants who reported a subsequent score in the normal range. Conclusions: In this current population, with a substantial proportion reporting treatment with a complement inhibitor, a diagnosis of PNH was associated with substantial symptom burden and impairment of quality of life. This preliminary investigation of longitudinal trends suggests some potential decreases over time but, for most participants, substantial burden and impairment persists. Next steps will be to assess the impact looking at more granular changes in symptoms and QoL and the impact of treatment and other demographic and disease factors to characterize the patterns over time. These data provide an important resource for understanding the real-world, lived experiences of individuals with PNH and to investigate long-term outcomes as care and treatment for this disease continues to evolve.