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
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
Myriam Alexander - Collaborator - OPEN Health Group
Stephen Boult - Collaborator - Harvey Walsh Ltd
Zalmai Hakimi - Collaborator - Swedish Orphan Biovitrum AB ( SOBI )
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation