US Optum Database Study in Polycythemia Vera Patients: Thromboembolic Events (TEs) with Hydroxyurea (HU) Vs Ruxolitinib Switch Therapy and Machine-Learning Model to Predict Incidence of Tes and HU Failure

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.1659-1659
• Main Authors: Verstovsek, Srdan, De Stefano, Valerio, Heidel, Florian H., Zuurman, Mike, Zaiac, Michael, Bigan, Erwan, Ruhl, Michael, Meier, Christoph, Beffy, Magali, Kiladjian, Jean-Jacques
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-126410

Introduction: Thromboembolic events (TEs) are one of the most prevalent complications in patients (pts) with polycythemia vera (PV). This real-world evidence study of the US OPTUM database evaluated the incidence of TEs in hydroxyurea (HU)-treated PV pts who either switched to ruxolitinib (RUX) after initial treatment (Tx) with HU (HU-RUX group) or continued HU Tx without switching (HU-alone group). Machine learning was then used to build a precise and scientifically robust model to predict the occurrence of TEs in PV pts with/without a history of TEs and HU failure (defined by either European LeukemiaNet [ELN] hematologic criteria or TEs). Methods: The OPTUM database comprises claims data and electronic medical records from 90 million pts (2007-2017, median stay in the database=7 years), including 69,464 PV pts. To avoid any selection bias during comparison, only pts treated prior to the RUX market launch were included in the HU-alone group (HU-RUX, n=81; HU-alone, n=195). Due to unavailability of Tx duration, time difference between the first and the last prescription was used as a proxy, and overall Tx duration was matched in both groups. TEs were assessed before Tx initiation in both groups. For HU-RUX pts, it was also assessed while on HU (median duration 27 months) and on RUX (median duration 14 months). For HU-alone pts, it was assessed during the first 27 months of Tx (any pt included in the analysis was treated for longer than this due to duration matching) and during remaining period of Tx (median duration 14 months). TEs were identified by either a restrictive definition (a list of ICD codes containing keywords from the RESPONSE study was automatically generated and manually curated) or a less restrictive one (list of ICD codes was manually expanded to include any TEs matching those from the GEMFIN study). PV pts who were exclusively treated with HU for ≥6 months were selected (n=2057) for modeling. Outcomes to be predicted were TEs in the 12 months following the end of the 6-month HU Tx period, and HU failure within 3 months of Tx. A logistic regression model was used for prediction. The baseline features extracted from the database included median lab parameters (3-6 months after HU initiation), history of thrombosis prior to primary diagnosis of PV, sociological features (age, gender), comorbidities, and concomitant medications (from inpatient/outpatient tables). Performance assessment methods included Receiver Operating Characteristic-Area U