Paroxysmal nocturnal haemoglobinuria (PNH) is a rare condition which affects patients’ blood composition by causing destruction of red blood cells, and for which treatment options remain limited. Apart from curative but risky stem-cell transplant, the main alternative currently is bi-monthly injection of C5 complement inhibitor. Due to PNH rarity, information remains scarce in England on who the adult patients are, how they are treated and how much of a burden on the National Health Service (NHS) is represented by PNH in both primary and secondary care settings. In this context, the objectives of this study are firstly to describe adult patients with PNH in terms of their demographic and clinical characteristics at the time they are being diagnosed and subsequently; and secondly to describe the treatment that patients are receiving for PNH, their risk of dying from PNH or other causes, and their use of NHS services. Both objectives will be evaluated separately in patients treated with or without C5 complement inhibitors, to better understand in particular the impact of this therapy on patients’ burden. As such, this study will require extraction of information on characteristics, treatment and resource use from both HES and CPRD from patients with PNH, during baseline prior to diagnosis and also after diagnosis until data cut. Information extracted from this study will enable a better assessment of the unmet need in patients with PNH, and raise awareness of the burden of PNH on the NHS for patients treated with or without C5 complement inhibitors.
PNH is a rare genetic hematological disorder due to hematopoietic stem-cell dysregulations and symptomatically associated with haemolytic anaemia, thrombosis and peripheral blood cytopenias. Hematopoietic stem-cell transplant is a curative but risky procedure, and treatment with monoclonal antibody C5 complement inhibitors eculizumab (available since 2007 in the United Kingdom ) and ravulizumab (since 2021) are main alternatives. Due to PNH rarity, there remains a paucity of evidence in England on patients’ characteristics, treatment patterns, and burden placed on the NHS in terms of primary and secondary healthcare resource use. In this context, we undertake a study firstly to better characterise the adult PNH patient population in terms of demographics and clinical characteristics at the time of diagnosis and also post-diagnosis; and also secondly to describe patients’ treatment patterns, mortality and healthcare resource use (HCRU) in primary and secondary care settings. As evidence is specifically lacking in patients treated with C5 complement inhibitors, the objectives of the study will be undertaken separately in patients receiving / not receiving this treatment following diagnosis. The following information will be extracted: demographic characteristics, comorbidities and symptoms (from HES and CPRD); primary care diagnoses, weight, smoking status, and visits (from CPRD); diagnoses, HCRU (inpatient, outpatient and Accident & Emergency attendances), high-cost drug treatment in secondary care settings and death date (from HES-ONS). This study will be descriptive, reporting summary statistics of frequencies and percentages for categorical variables and means (attendances and associated costs per patient-year for HCRU), standard deviations, medians, interquartile ranges, and range for continuous variables; with 95% confidence intervals to be derived for proportions and means, whenever appropriate. Survival rates will be summarised using Kaplan-Meier methodology. These estimates will provide real-word information on the burden of PNH and support assessment of the unmet need in this rare patient population with limited options for treatment.
Age; sex; index of multiple deprivation; ethnicity; Charlson Comorbidity Index; weight; smoking status; co-morbidities and symptoms (tiredness; haemoglobinuria; abdominal pain; shortness of breath / dyspnoea; major adverse vascular event / thrombosis; dysphagia; erectile dysfunction; anaemia including aplastic anaemia; myeloblastic syndrome; immunosuppression in solid organ transplantation; disorder of iron metabolism; amyloid A amyloidosis; multiple myeloma), treatment (red blood cell transfusions; folic acid prescriptions; iron tablets prescriptions; anti-coagulant treatments; C5 complement inhibitor treatment; iron-chelation therapy; hematopoietic stem-cell transplant (HSCT)); full blood counts tests and results including serum iron levels; death; primary and secondary healthcare resource use HCRU (general practitioner contacts; outpatient visits and departments; elective and non-elective inpatient diagnoses, spells and length of stay; Accident and Emergency department attendance) and associated HCRU cost.
- Chief Investigator -
Ellen Hubbuck - Corresponding Applicant - Pharmatelligence Limited t/a Human Data Sciences
- Collaborator -
Carly Rich - Collaborator - Swedish Orphan Biovitrum AB ( SOBI )
Jameel Nazir - Collaborator - Swedish Orphan Biovitrum AB ( SOBI )
Koo Wilson - Collaborator - Swedish Orphan Biovitrum AB ( SOBI )
Laura Tolan - Collaborator - OPEN Health Group
Mark Evans - Collaborator - OPEN Health Group
Stephen Boult - Collaborator - Harvey Walsh Ltd
Zalmai Hakimi - Collaborator - Swedish Orphan Biovitrum AB ( SOBI )
Myriam Alexander - Collaborator - Harvey Walsh Ltd
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation