Baseline Characteristics of Patients with Paroxysmal Nocturnal Hemoglobinuria Identified in the Department of Defense Database
Authors: Ulcickas Yood Marianne , Jick Susan , Vasilakis-Scaramozza Catherine , Donato Bonnie M.K. , Tomazos Ioannis , L'Italien Gilbert , Sicignano Nicholas , Feldman Brian L. 
Published: October 2019

Abstract
Background: Rare diseases are often characterized by misdiagnosis resulting in delays in critical and potentially lifesaving treatment. Awareness of first signs and symptoms of rare diseases can provide clinical evidence for early and accurate diagnosis. Medical records are the primary source of clinical information from first signs and symptoms to key clinical disease related events, yet access to records can be difficult and time consuming. We conducted a study using a large electronic medical record (EMR) and claims database to identify and describe characteristics of Paroxysmal Nocturnal Hemoglobinuria (PNH) patients at the time of their PNH diagnosis. We present baseline findings of the PNH population identified in the Department of Defense (DOD) healthcare system, where all clinical details were readily available. The DOD healthcare system is a US-based, longitudinal EMR and claims database with health information on approximately 10 million active beneficiaries throughout the country.
Methods: We identified all people in the DOD database from January 01, 2007 through May 31, 2017 who had an ICD-10-CM code for PNH or a NDC or HCPCS code for eculizumab, the drug used to treat PNH. There is no ICD-9-CM code for PNH. Cases had no other indication for eculizumab use and had to have appropriate symptoms, comorbidities or lab results to be considered a case. We reviewed the electronic record for each patient and classified each as definite/likely, probable/possible or unlikely PNH based on attributes of the available health data including codes for eculizumab, flow cytometry, lab results, hemoglobinuria, aplastic anemia, pancytopenia and other comorbidities. Our ruling was validated by medical record review by a clinical expert for all equivocal cases and a sample of definite/likely cases. Individuals classified as unlikely PNH were excluded. Patient characteristics at PNH diagnosis are presented using descriptive statistics.
Results: We identified 73 PNH patients (55% female) after review of all available electronic data; 41 had a diagnosis of PNH and received eculizumab, 17 had a diagnosis of PNH only, and 15 received eculizumab only. From these, 61 patients were determined to have definite/likely PNH and 12 had probable/possible PNH. The use of eculizumab ranged from 0 to 378 (median=18) prescriptions, dependent in part on the amount of follow-up in the database. There were 19 patients (26%) who had prevalent PNH and 54 (74%) who were newly diagnosed with PNH during the study period. Among newly diagnosed patients, the median age at PNH diagnosis was 46 years (range 13 - 86). Most patients had codes for hemoglobinuria at or before the PNH diagnosis date (69%), and many had codes for aplastic anemia (46%), thrombocytopenia (56%), and pancytopenia (28%). At any time after the PNH diagnosis, 85% had unspecified anemia, 52% had aplastic anemia, 53% had thrombocytopenia, and 33% had pancytopenia codes in their records. See table.
Conclusion: From a population of around 10 million actively enrolled patients, across a 10-year study period, we identified 73 patients with PNH. Data from these patients will be used to identify patterns of health encounters leading up to diagnosis and relevant outcomes following diagnosis. This information can be used to help diagnose other patients with this rare disease and to improve their medical outcomes.
Disclaimer Statement: Research data were derived from an approved Naval Medical Center, Portsmouth, VA IRB protocol (NMCP.2017.0080). The views expressed in this abstract are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense or the United States Government. Copyright Notice: CAPT Brian Feldman is a military service member. This work was prepared as part of his official duties. Title 17 U.S.C. 105 provides that 'Copyright protection under this title is not available for any work of the United States Government.'
Title 17 U.S.C. 101 defines a United States Government work as a work prepared by a military service member or employee of the United States Government as part of that person's official duties.
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Disclosures
Ulcickas Yood: Alexion Pharmaceuticals, Inc.: Other: Employee of EpiSource, LLC, which was contracted by Alexion Pharmaceuticals, Inc. EpiSource had the final decision on content. . Jick:Alexion Pharmaceuticals, Inc.: Other: Employee of the Boston Collaborative Drug Surveillance Program, which was contracted and paid by Alexion Pharmaceuticals, Inc. to work on a study of PNH using DOD data. . Vasilakis-Scaramozza:Alexion Pharmaceuticals, Inc.: Other: Employee of the Boston Collaborative Drug Surveillance Program, which was contracted and paid by Alexion Pharmaceuticals, Inc. to work on a study of PNH using DOD data.. Donato:Alexion Pharmaceuticals Inc: Employment, Equity Ownership. Tomazos:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. L'Italien:Alexion Pharmaceuticals, Inc.: Equity Ownership, Other: Former employee and current stockholder of Alexion Pharmaceuticals, Inc. . Sicignano:Alexion Pharmaceuticals, Inc.: Other: Employee of Health ResearchTx, which has a business relationship with Alexion Pharmaceuticals, Inc.. Feldman:Alexion Pharmaceuticals, Inc.: Other: Employee, Department of Navy, United States Government..