Jia Li1, Mei Lu2, Yueren Zhou2, Christopher L Bowlus3, Keith Lindor4, Carla Rodriguez-Watson5,6, Robert J Romanelli7, Irina V Haller8, Heather Anderson9, Jeffrey J VanWormer10, Joseph A Boscarino11, Mark A Schmidt12, Yihe G Daida13, Amandeep Sahota14, Jennifer Vincent15, Kuan-Han Hank Wu2, Sheri Trudeau2, Loralee B Rupp16, Christina Melkonian2, Stuart C Gordon17. 1. Department of Public Health Sciences, Henry Ford Health System, 3E One Ford Place, Detroit, MI, 48202, USA. jli4@hfhs.org. 2. Department of Public Health Sciences, Henry Ford Health System, 3E One Ford Place, Detroit, MI, 48202, USA. 3. University of California Davis School of Medicine, Sacramento, CA, USA. 4. College of Health Solutions, Arizona State University, Phoenix, AZ, USA. 5. Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville, MD, USA. 6. Innovation in Medical Evidence Development and Surveillance, The Reagan-Udall Foundation for the FDA, Washington, DC, USA. 7. Palo Alto Medical Foundation Research Institute, Palo Alto, CA, USA. 8. Essentia Institute of Rural Health, Essentia Health, Duluth, MN, USA. 9. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA. 10. Marshfield Clinic Research Institute, Marshfield, WI, USA. 11. Department of Epidemiology and Health Services Research, Geisinger Clinic, Danville, PA, USA. 12. Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA. 13. Center for Integrated Health Care Research, Kaiser Permanente Hawaii, Honolulu, HI, USA. 14. Department of Research and Evaluation, Kaiser Permanente Southern California, Los Angeles, CA, USA. 15. Baylor, Scott & White Research Institute, Temple, TX, USA. 16. Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA. 17. Department of Gastroenterology and Hepatology, Henry Ford Health System, and Wayne State University School of Medicine, Detroit, MI, USA.
Abstract
BACKGROUND: Ursodeoxycholic acid (UDCA) remains the first-line therapy for primary biliary cholangitis (PBC); however, inadequate treatment response (ITR) is common. The UK-PBC Consortium developed the modified UDCA Response Score (m-URS) to predict ITR (using alkaline phosphatase [ALP] > 1.67 times the upper limit of normal [*ULN]) at 12 months post-UDCA initiation). Using data from the US-based Fibrotic Liver Disease Consortium, we assessed the m-URS in our multi-racial cohort. We then used a dynamic modeling approach to improve prediction accuracy. METHODS: Using data collected at the time of UDCA initiation, we assessed the m-URS using the original formula; then, by calibrating coefficients to our data, we also assessed whether it remained accurate when using Paris II criteria for ITR. Next, we developed and validated a dynamic risk prediction model that included post-UDCA initiation laboratory data. RESULTS: Among 1578 patients (13% men; 8% African American, 9% Asian American/American Indian/Pacific Islander; 25% Hispanic), the rate of ITR was 27% using ALP > 1.67*ULN and 45% using Paris II criteria. M-URS accuracy was "very good" (AUROC = 0.87, sensitivity = 0.62, and specificity = 0.82) for ALP > 1.67*ULN and "moderate" (AUROC = 0.74, sensitivity = 0.57, and specificity = 0.70) for Paris II. Our dynamic model significantly improved accuracy for both definitions of ITR (ALP > 1.67*ULN: AUROC = 0.91; Paris II: AUROC = 0.81); specificity approached 100%. Roughly 9% of patients in our cohort were at the highest risk of ITR. CONCLUSIONS: Early identification of patients who will not respond to UDCA treatment using a dynamic prediction model based on longitudinal, repeated risk factor measurements may facilitate earlier introduction of adjuvant treatment.
BACKGROUND: Ursodeoxycholic acid (UDCA) remains the first-line therapy for primary biliary cholangitis (PBC); however, inadequate treatment response (ITR) is common. The UK-PBC Consortium developed the modified UDCA Response Score (m-URS) to predict ITR (using alkaline phosphatase [ALP] > 1.67 times the upper limit of normal [*ULN]) at 12 months post-UDCA initiation). Using data from the US-based Fibrotic Liver Disease Consortium, we assessed the m-URS in our multi-racial cohort. We then used a dynamic modeling approach to improve prediction accuracy. METHODS: Using data collected at the time of UDCA initiation, we assessed the m-URS using the original formula; then, by calibrating coefficients to our data, we also assessed whether it remained accurate when using Paris II criteria for ITR. Next, we developed and validated a dynamic risk prediction model that included post-UDCA initiation laboratory data. RESULTS: Among 1578 patients (13% men; 8% African American, 9% Asian American/American Indian/Pacific Islander; 25% Hispanic), the rate of ITR was 27% using ALP > 1.67*ULN and 45% using Paris II criteria. M-URS accuracy was "very good" (AUROC = 0.87, sensitivity = 0.62, and specificity = 0.82) for ALP > 1.67*ULN and "moderate" (AUROC = 0.74, sensitivity = 0.57, and specificity = 0.70) for Paris II. Our dynamic model significantly improved accuracy for both definitions of ITR (ALP > 1.67*ULN: AUROC = 0.91; Paris II: AUROC = 0.81); specificity approached 100%. Roughly 9% of patients in our cohort were at the highest risk of ITR. CONCLUSIONS: Early identification of patients who will not respond to UDCA treatment using a dynamic prediction model based on longitudinal, repeated risk factor measurements may facilitate earlier introduction of adjuvant treatment.
Authors: Stuart C Gordon; Kuan-Han Hank Wu; Keith Lindor; Christopher L Bowlus; Carla V Rodriguez; Heather Anderson; Joseph A Boscarino; Sheri Trudeau; Loralee B Rupp; Irina V Haller; Robert J Romanelli; Jeffrey J VanWormer; Mark A Schmidt; Yihe G Daida; Amandeep Sahota; Jennifer Vincent; Talan Zhang; Jia Li; Mei Lu Journal: Am J Gastroenterol Date: 2020-02 Impact factor: 10.864
Authors: Marco Carbone; Alessandra Nardi; Steve Flack; Guido Carpino; Nikoletta Varvaropoulou; Caius Gavrila; Ann Spicer; Jonathan Badrock; Francesca Bernuzzi; Vincenzo Cardinale; Holly F Ainsworth; Michael A Heneghan; Douglas Thorburn; Andrew Bathgate; Rebecca Jones; James M Neuberger; Pier Maria Battezzati; Massimo Zuin; Simon Taylor-Robinson; Maria F Donato; John Kirby; Robert Mitchell-Thain; Annarosa Floreani; Fotios Sampaziotis; Luigi Muratori; Domenico Alvaro; Marco Marzioni; Luca Miele; Fabio Marra; Edoardo Giannini; Eugenio Gaudio; Vincenzo Ronca; Giulia Bonato; Laura Cristoferi; Federica Malinverno; Alessio Gerussi; Deborah D Stocken; Heather J Cordell; Gideon M Hirschfield; Graeme J Alexander; Richard N Sandford; David E Jones; Pietro Invernizzi; George F Mells Journal: Lancet Gastroenterol Hepatol Date: 2018-07-13