Profile of Pain Medication Use in Hemophilia and Hemarthrosis: An Analysis of a Pharmacy Claims Database
Authors: Mauer Kim , Helm Travis , Buckner Tyler W. , Macgregor Corey , Boice Judith A. , Cerasoli Frank , Khan Tahmid , Argoff Charles 
Published: November 2021

Abstract
Introduction: Chronic joint pain associated with bleeding disorders (particularly Hemophilia A and Hemophilia B) is well characterized. The most common treatments reported by patients with bleeding disorders include acetaminophen, traditional nonsteroidal anti-inflammatory drugs (tNSAIDs; cyclooxygenase 1/2 inhibitors, COX-1/2), COX-2 selective NSAIDs, and opioids (Witkop, et al. Haemophilia . 2017;23:556). Up to 50% of patients have reported opioid use to manage both acute and chronic pain(Witkop, et al. Haemophilia . 2017;23:556). The aim of this study was to compare and analyze different types of prescription pain medications in patients with a diagnosis of hemophilia A, B, and hemarthrosis using a pharmacy claims database. Methods: A cross-sectional analysis was conducted on a retrospective cohort of patients with bleeding disorders receiving pain medications in the Truven Health MarketScan Commercial Claims and Encounters database, for which IRB approval was not required. Index encounters were reported from April 1, 2017 to March 30, 2018, with one year of follow up. Patients were outpatients, inpatients, or both. Patient-level demographics were not collected. Results: Unique patients totaling 876 received 5,702 prescriptions. Patient diagnosis codes included Hemophilia A (D66), Hemophilia B (D67), and hemarthrosis (M362), each of which contributed 79.2%, 11.9%, and 8.8%, respectively, to the total prescriptions. Outpatient prescriptions comprised 81.0% of total prescriptions. Scheduled prescriptions comprised 70.8% of all prescriptions, 81.7% of inpatient prescriptions, and 68.2% of outpatient prescriptions (see Table). Schedule II drugs comprised 82.6% and 77.3% of all scheduled inpatient and outpatient prescriptions, respectively (see Table). Schedule IV prescriptions were the next most common, followed by schedule III. Prescription NSAIDs were more common in the outpatient than in the inpatient setting (see Table). Among NSAIDs, celecoxib comprised approximately half of the outpatient NSAID prescriptions and 15.1% of all outpatient prescriptions. Discussion: Regardless of setting, schedule II drugs are the most common form of pain management prescription in patients with hemophilia or hemarthrosis. Prescriptions for scheduled medications appear similar to what might be inferred in previous studies of patient reported use (Witkop, et al. Haemophilia . 2017;23:556). Consistent with self-reports (Witkop, et al. Haemophilia . 2017;23:556), hydrocodone or oxycodone with acetaminophen were confirmed to be the most frequently prescribed schedule II opioids. tNSAIDs, such as those reported in this analysis share gastrointestinal (GI) bleeding risk which may be heightened in persons with hemophilia compared with those who have no bleeding disorders. Celecoxib represents approximately 50% of outpatient NSAID prescriptions in this analysis despite data showing its clinically significant GI event risk is similar to both ibuprofen and naproxen (Nissen, et al. N Engl J Med. 2016:2519). Over-the counter acetaminophen is commonly used to treat chronic joint pain in hemophilia (Witkop, et al. Haemophilia. 2017;23:556) presumably to avoid GI bleeding, yet is reported to be less efficacious than celecoxib (Rodriguez-Merchan, et al. Blood Rev. 2018: 116). The broad use of opioids with their attendant risk of misuse, addiction, and diversion; as well as tNSAIDs, with their attendant GI risks, underscores the limited pain management options available for persons with hemophilia. This cross-sectional prescription claims data analysis highlights the need to identify and develop alternate forms of chronic pain medications for this population who have unique unmet needs (Humphries, et al. Haemophilia. 2015:41).
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Disclosures
Helm: Tremeau Pharmaceuticals Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Buckner: Genetech: Honoraria; Spark: Honoraria; Sanofi: Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Takeda: Honoraria; American Thrombosis: Membership on an entity's Board of Directors or advisory committees; Hemostasis Network: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Honoraria; CSL Behring: Honoraria; Tremeau Pharmaceuticals: Consultancy, Honoraria; uniQure: Consultancy, Honoraria; BioMarin: Consultancy, Honoraria. Macgregor: Tremeau Pharmaceuticals Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Boice: Tremeau Pharmaceuticals Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Cerasoli: RX Medical Dynamics LLC: Consultancy, Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Khan: Rx Medical Dynamics, LLC: Current Employment. Argoff: Tremeau Pharmaceuticals,Inc: Consultancy.