Frank I Scott1, Mark T Osterman, Ryan A McConnell, Monica Lorusso, Faten Aberra, Caroline Kerner, Gary R Lichtenstein, James D Lewis. 1. *Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania; †Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; ‡Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and §Division of Gastroenterology and Nutrition, Department of Paediatrics, Anna Meyer Children's Hospital, University of Florence, Florence, Italy.
Abstract
BACKGROUND: The optimal treatment strategy for patients with Crohn's disease who have loss of response to the anti-tumor necrosis factor α medication infliximab is uncertain. Natalizumab has an alternative mechanism of action, but its use has been limited by the risk of progressive multifocal leukoencephalopathy. In this study, we performed a decision analysis assessing the impact of JC virus (JCV) antibody testing and natalizumab utilization for loss of response to infliximab. METHODS: We constructed a Markov model to assess the difference between unscreened natalizumab use (option 1), JCV antibody testing with natalizumab when appropriate (option 2), and second anti-tumor necrosis factor α use (option 3). The base case was a 35-year-old man with severe Crohn's disease with loss of response to infliximab. The time horizon was 3 years. Results are reported in quality-adjusted life years (QALYs). Deterministic and probabilistic analyses were conducted. Markov analysis using a cohort of 5000 individuals was performed. The impact of JCV antibody status on outcomes in this model was assessed. RESULTS: Option 2 was the preferred strategy (2.0880 QALYs), followed by option 1 (2.0875 QALYs) and option 3 (2.0808 QALYs). Patients in option 2 required fewer surgeries compared with option 3. Previous JCV infection was associated with reduced QALYs with all options that allowed for natalizumab use. CONCLUSIONS: JCV antibody testing and subsequent treatment selection yield improved outcomes over natalizumab without testing or using only a second anti-tumor necrosis factor α in all patients.
BACKGROUND: The optimal treatment strategy for patients with Crohn's disease who have loss of response to the anti-tumor necrosis factor α medication infliximab is uncertain. Natalizumab has an alternative mechanism of action, but its use has been limited by the risk of progressive multifocal leukoencephalopathy. In this study, we performed a decision analysis assessing the impact of JC virus (JCV) antibody testing and natalizumab utilization for loss of response to infliximab. METHODS: We constructed a Markov model to assess the difference between unscreened natalizumab use (option 1), JCV antibody testing with natalizumab when appropriate (option 2), and second anti-tumor necrosis factor α use (option 3). The base case was a 35-year-old man with severe Crohn's disease with loss of response to infliximab. The time horizon was 3 years. Results are reported in quality-adjusted life years (QALYs). Deterministic and probabilistic analyses were conducted. Markov analysis using a cohort of 5000 individuals was performed. The impact of JCV antibody status on outcomes in this model was assessed. RESULTS: Option 2 was the preferred strategy (2.0880 QALYs), followed by option 1 (2.0875 QALYs) and option 3 (2.0808 QALYs). Patients in option 2 required fewer surgeries compared with option 3. Previous JCVinfection was associated with reduced QALYs with all options that allowed for natalizumab use. CONCLUSIONS:JCV antibody testing and subsequent treatment selection yield improved outcomes over natalizumab without testing or using only a second anti-tumor necrosis factor α in all patients.
Authors: D H Present; P Rutgeerts; S Targan; S B Hanauer; L Mayer; R A van Hogezand; D K Podolsky; B E Sands; T Braakman; K L DeWoody; T F Schaible; S J van Deventer Journal: N Engl J Med Date: 1999-05-06 Impact factor: 91.245
Authors: Corey A Siegel; Samuel R G Finlayson; Bruce E Sands; Anna N A Tosteson Journal: Clin Gastroenterol Hepatol Date: 2011-10-01 Impact factor: 11.382
Authors: Gary Bloomgren; Sandra Richman; Christophe Hotermans; Meena Subramanyam; Susan Goelz; Amy Natarajan; Sophia Lee; Tatiana Plavina; James V Scanlon; Alfred Sandrock; Carmen Bozic Journal: N Engl J Med Date: 2012-05-17 Impact factor: 91.245
Authors: David B Clifford; Andrea De Luca; Andrea DeLuca; David M Simpson; Gabriele Arendt; Gavin Giovannoni; Avindra Nath Journal: Lancet Neurol Date: 2010-04 Impact factor: 44.182
Authors: Jean-Frédéric Colombel; William J Sandborn; Paul Rutgeerts; Robert Enns; Stephen B Hanauer; Remo Panaccione; Stefan Schreiber; Dan Byczkowski; Ju Li; Jeffrey D Kent; Paul F Pollack Journal: Gastroenterology Date: 2006-11-29 Impact factor: 22.682
Authors: Jean Frédéric Colombel; William J Sandborn; Walter Reinisch; Gerassimos J Mantzaris; Asher Kornbluth; Daniel Rachmilewitz; Simon Lichtiger; Geert D'Haens; Robert H Diamond; Delma L Broussard; Kezhen L Tang; C Janneke van der Woude; Paul Rutgeerts Journal: N Engl J Med Date: 2010-04-15 Impact factor: 91.245
Authors: Corey A Siegel; Sadie M Marden; Sarah M Persing; Robin J Larson; Bruce E Sands Journal: Clin Gastroenterol Hepatol Date: 2009-01-24 Impact factor: 11.382