The Global Paroxysmal Nocturnal Hemoglobinuria (PNH) Patient Registry: Highlights of the Data from the First Three Years

Background: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, acquired, hematologic disorder characterized by chronic complement-mediated hemolysis and associated with a mutation in the PIG-A gene, thrombosis, and immune-mediated marrow failure. The Global PNH Patient Registry, initiated in 2021, is the first patient-driven and patient-focused PNH registry. The Aplastic Anemia and MDS International Foundation leads The Global PNH Patient Registry with input from patients and caregivers along with hematologists and researchers. All data are provided by individuals with PNH or their caregivers. The goals are to: 1) enhance the understanding of PNH, 2) identify gaps and improve the care of patients with PNH, and 3) empower and unite the PNH community.

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, have a computer or mobile device, and have access to the internet. The study was reviewed and approved by North Star Review Board (IRB #NB100005). Study participants provide information on demographics, diagnosis, history of procedures, medications and supplements, current symptoms, health care utilization and quality of life. After the initial survey completion, participants are notified every 6 months to update information. This analysis includes the initial completion of each survey entered between April 2021 and April 2024. The data was analyzed to provide counts, percentages and mean values. Quality of life was measured by using select PROMIS® measures that were scored and transformed to standardized t-score values using the PROMIS Scoring Manuals (www.healthmeasures.net).

Results: 173 people consented to participate and completed at least one survey in. The Global PNH Patient Registry participants are 99% adults with 60% aged 18 to 50 and 39% aged 50 and older. 65% of participants are female and 11% affiliate with the LGBTQ+ community. 15% are Hispanic, 12% are Asian, 6 % are Black or African American and 77% are White. 69% of participants live in the United States. The average age of symptom onset and diagnosis was 34 and 36 respectively. 43% reported having been diagnosed within 6 months of symptoms and 31% reported 2 or more years to receive a diagnosis. Receipt of a flow cytometry test, the definitive diagnostic tool, was reported by 67% of participants. Co-morbid conditions were reported by 55% of participants with aplastic anemia being the most commonly reported (38%). Fatigue was the most reported symptom with 64% indicating that they experience it “Often” or “Almost Always”. The next were lower back pain (39%), “brain fog” (38%), bruising easily (37%) and joint pain (36%). Most participants have a PNH-related care visit at least once a month with 61% reporting 7 or more in the past 6 months. Medication use was reported by 92% of participants, with 68% reporting having ever taken a complement inhibitor. PROMIS quality of life instruments that measured emotional support, depression and pain interference had average scores that were comparable to the general population. The instruments measuring fatigue, anxiety and participation in social activities had average scores indicating mild impairment and the average scores for physical function indicated moderate impairment compared to the general population (median: 34, 10th percentile 23, 90th percentile 42). At the individual level, more than half of individuals had scores indicating impairment with 35% of individuals had scores indicating severe impairment of physical function.

Conclusions: The Global PNH Patient Registry highlights the power and potential of patient-reported data to provide meaningful insights on the natural history of PNH in a clinically and demographically diverse population. Plans include expanding recruitment and retention efforts, translating the registry into Spanish, examining the longitudinal data, and developing processes to broaden the use of the data within the community. Considering the evolving landscape of anti-complement therapeutic options available for patients, we believe this registry will be invaluable for monitoring the experience of individuals living with PNH in an increasingly complex field.