Mortality among US veterans with a physician-documented diagnosis of pyruvate kinase deficiency

ABSTRACT

Real-world studies of pyruvate kinase (PK) deficiency and estimates of mortality are lacking. This retrospective observational study aimed to identify patients with PK deficiency and compare their overall survival (OS) to that of a matched cohort without PK deficiency. Patients with ≥1 diagnosis code related to PK deficiency were selected from the US Veterans Health Administration (VHA) database (01/1995–07/2019); patients with a physician-documented diagnosis were included (PK deficiency cohort; index: date of first diagnosis code related to PK deficiency). Patients in the PK deficiency cohort were matched 1:5 to patients from the general VHA population (non-PK deficiency cohort; index: random visit date during match’s index year). OS from index was compared between the two cohorts. Eighteen patients in the PK deficiency cohort were matched to 90 individuals in the non-PK deficiency cohort (both cohorts: mean age 57 years, 94% males; median follow-up 6.0 and 8.0 years, respectively). At follow-up, patients in the non-PK deficiency cohort had significantly longer OS than the PK deficiency cohort (median OS: 17.1 vs. 10.9 years; hazard ratio: 2.3; p = 0.0306). During their first-year post-index, 75% and 40% of the PK deficiency cohort had laboratory-confirmed anemia and iron overload, respectively. Among patients who died, cause of death was highly heterogeneous. These results highlight the increased risk of mortality and substantial clinical burden among patients with PK deficiency. While the intrinsic characteristics of the VHA database may limit the generalizability of the results, this is the first real-world study to characterize mortality in patients with PK deficiency.

KEYWORDS:

• anemia
• hemolytic
• mortality
• pyruvate kinase deficiency
• Veterans Health Administration

Acknowledgments

Medical writing and editorial assistance was provided by Mona Lisa Chanda, PhD, an employee of Analysis Group, Inc. Support for this assistance was provided by Agios Pharmaceuticals, Inc.

Funding details

This work was funded by Agios Pharmaceuticals, Inc.

Disclosure statement

Erin Zagadailov was an employee and stockholder of Agios Pharmaceuticals, Inc. at the time of the development of this project, and an employee of Takeda Oncology within the 3 years prior to the development of this project. Audra N. Boscoe and Bryan McGee are employees and stockholders of Agios Pharmaceuticals, Inc. Hanny Al-Samkari was a consultant for Agios, argenx, Sobi, Moderna, Novartis, Rigel, Forma and received research funding from Agios, Amgen, Sobi. Viviana Garcia-Horton and Sherry Shi are employed by Analysis Group, Inc., which received payment from Agios Pharmaceuticals, Inc. for participation in this research. Lizheng Shi has a research contract and received consulting fees from Analysis Group, Inc. Dendy Macaulay was an employee of Analysis Group, Inc. at the time of this project.

Data availability statement

The dataset supporting the conclusions in this article is available from the US VHA, which we had full permissions to access and use for this study. However, restrictions apply to the availability of these data, which were used under license for the current study, and are therefore not publicly available.

Additional information

Notes on contributors

Erin Zagadailov

Erin Zagadailov is a former Director of Health Economics & Outcomes Research (HEOR) at Agios Pharmaceuticals and is a biotech executive with experience in patient-focused drug development, real-world evidence, and health economics. She is currently the Chief Innovation Officer at Clinical Outcomes Research Group, LLC. Her research has been published in The New England Journal of Medicine, The Lancet, and the British Journal of Hematology, among other major peer-reviewed journals.

Hanny Al-Samkari

Hanny Al-Samkari is an Assistant Professor of Medicine at Harvard Medical School as well as an NIH-funded clinical investigator and classical hematologist at the Massachusetts General Hospital (MGH) Division of Hematology Oncology. He also serves as Co-Director the MGH Hereditary Hemorrhagic Telangiectasia (HHT) Center of Excellence. His clinical and research interests are in hemostasis, thrombosis and hemolysis, with focuses in HHT, immune thrombocytopenia, and hereditary hemolytic anemias. He currently serves as PI for many clinical trials in these areas and is a recognized expert in the clinical development of novel therapeutics for HHT, hemolytic anemias and immune thrombocytopenia. He is the current Executive Editor of Hematology: The ASH Education Program, an American Society of Hematology peer-reviewed publication, and has published over 130 peer-reviewed manuscripts. His original research has been featured in The New England Journal of Medicine, The Lancet, and Blood, among other major peer-reviewed journals in hematology and medicine.

Audra N. Boscoe

Audra N. Boscoe leads the Health Economics, Outcomes Research & Data Science Analytics department at Agios Pharmaceuticals. Her areas of specialty include real-world evidence generation using a variety of data sources (disease registries, surveys, electronic medical records, and administrative claims databases), economic modeling, and patient-reported outcomes. Her career has spanned a variety of therapeutic areas including oncology, hematology, cardiology, nephrology, and neurology, with a particular focus on rare diseases. Dr. Boscoe has published numerous articles in peer-reviewed journals and presented her original research at a number of clinical and health economics and outcomes research conferences.

Bryan McGee

Bryan McGee is a Sr. Medical Director for the PK deficiency program at Agios Pharmaceuticals, Inc. He currently serves as the medical affairs lead for the PK deficiency Peak registry, is a member of the Peak Registry Steering Committee, and has co-authored multiple abstract and manuscript submissions on the burden of disease in PK deficiency. His career has spanned a variety of therapeutic areas including hematology, rheumatology, endocrinology, and pediatric/adult infectious disease with a particular focus on rare diseases.

Sherry Shi

Sherry Shi is a biostatistician who specializes in health economics and outcomes research (HEOR), biostatistics, and epidemiology. Her experience includes retrospective analyses of various data sources such as medical insurance claims and electronic medical records. Sherry has conducted data analysis in multiple clinical areas, such as oncology, hematology, and gastroenterology. Her research has been published in numerous peer-reviewed medical journals, including the Journal of Medical Economics (JME), the Journal of Comparative Effectiveness Research, Journal of Cancer Therapy. Prior to joining Analysis Group, Sherry was a research assistant at McGill University.

Dendy Macaulay

Dendy Macaulay is a former Vice President of Analysis Group and is an economist with extensive experience in the application of statistics and econometrics to health outcomes research. Her expertise includes retrospective claims analyses, patient chart reviews, clinical trial data analyses, economic modeling, and health economics and outcomes research strategy. Her work has involved the development economic models to evaluate Medicare demonstration projects and drug expansion into emerging markets; comparative effectiveness and cost effectiveness research; prediction algorithms; the assessment of disease prevalence, burden of illness, and treatment patterns; and the development pharmaceutical pricing strategies. Dr. Macaulay's experience encompasses a wide range of therapeutic areas, including oncology, mental health, respiratory, immunology, and other chronic disease areas with the use of multiple data sources, including clinical trial, Medicare, Medicaid, private insurance, electronic medical record, and patient chart review data. Her experience also includes analyses in support of health care commercial litigation related to patents and pharmaceutical licensing. Dr. Macaulay has published numerous articles in peer-reviewed journals, including Health Affairs, Respiratory Medicine, PharmacoEconomics, and The Journal of the American Geriatrics Society.

Lizheng Shi

Lizheng Shi is an Endowed Regents Professor and Interim Chair in the Department of Global Health Policy and Management in the Tulane University School of Public Health and Tropical Medicine (TUSPHTM). He is also the director for the Health Systems Analytics Research Center (HSARC) and a member of the editorial board for Pharmacoeconomics. Dr. Shi also has a joint appointment with the Department of Medicine at the Tulane University School of Medicine. His research interests include health technology assessments and health care quality, access, and economics. Prior to his appointment at Tulane, Dr. Shi held the position of Senior Health Outcomes Scientist at Eli Lilly and Company in Indianapolis.

Viviana Garcia-Horton

Viviana Garcia-Horton is a statistician who specializes in the application of advanced statistical techniques to the field of health economics and outcomes research (HEOR). She has broad experience developing research and strategies in a wide range of disease areas, including diabetes, oncology, hematology, rare diseases, dermatology, psychiatry, neurology, and gastroenterology. Dr. Garcia-Horton’s expertise includes causal inference for experimental and observational data, predictive modeling, missing data problems, Bayesian statistics, clinical trial design and analysis, indirect treatment comparisons, individualized medicine, and retrospective claims database analyses. Her work includes developing network meta-analyses for regulatory submission, treatment patterns and economic outcomes research using retrospective claims analyses, clinical trial data analyses, and analyses of patient-reported outcomes (PROs) to support approved product labeling. Dr. García-Horton’s research has been published in peer-reviewed journals and presented at numerous clinical research, health economics, and statistics conferences.