Fall Obesity Summit Precision Medicine in Obesity Aaron S. Kelly, Ph.D. Associate Professor of Pediatrics Minnesota American Legion and Auxiliary Chair in Children’s Health Co-Director, Center for Pediatric Obesity Medicine University of Minnesota Medical School 1 obesitymedicine.org Objectives • Describe the heterogeneity of response to various obesity treatments • Identify factors associated with favorable treatment outcomes • Characterize the future challenges and opportunities regarding precision medicine approaches for treatment of obesity 2 Precision Medicine in Obesity Treatment
Fall Obesity Summit Overview • Heterogeneity in treatment response • Prologue to precision obesity medicine: primordial predictors of response • Taking precision obesity medicine to the next level: potential predictors worthy of investigation • The future of precision obesity medicine – Challenges – Opportunities 3 Heterogeneity - Adult Lifestyle, Pharmacotherapy, Surgery 4 MacLean PS et al. Obesity 2018 Precision Medicine in Obesity Treatment
Fall Obesity Summit Heterogeneity - Pediatric Lifestyle, Pharmacotherapy, Surgery 5 Unpublished data Heterogeneity - Pediatric 6 Kelly AS et al. JAMA Pediatr 2013 Precision Medicine in Obesity Treatment
Fall Obesity Summit Sources of Heterogeneity • Genetic • Physiological • Behavioral • Psychosocial • Environmental • And more… 7 What is Precision Medicine? • Identification and characterization of sources of heterogeneity • Synthesis and application of this information to select appropriate treatment(s) with goal of maximizing benefit while minimizing risk • In other words, getting the right treatment to the right patient at the right time 8 Precision Medicine in Obesity Treatment
Fall Obesity Summit Primordial Predictors Previous Weight Loss Attempts 9 Carraca EV et al. Obesity Facts 2018 Primordial Predictors Early Weight Loss 10 Gross AC et al. Unpublished Precision Medicine in Obesity Treatment
Fall Obesity Summit Primordial Predictors Early Weight Loss 11 Fujioka K et al. Obesity 2016 Primordial Predictors Early Weight Loss 12 Courcoulas AP et al. JAMA Surg 2018 Precision Medicine in Obesity Treatment
Fall Obesity Summit Primordial Predictors Variability in Weight Loss Trajectory 13 Feig EH et al. Obesity 2017 Primordial Predictors Variability in Weight Loss Trajectory 14 Marek RJ et al. Obesity 2017 Precision Medicine in Obesity Treatment
Fall Obesity Summit Primordial Predictors Self-Report Appetite/Cognitive Restraint 15 Thomas EA et al. Obesity 2016 Primordial Predictors Sex and Self-Report Appetite 16 Nathan BM et al. Clin Obes 2016 Precision Medicine in Obesity Treatment
Fall Obesity Summit Primordial Predictors Eating Disorder Pathology 17 Balantekin KN et al. Obesity 2017 On the Horizon Areas Worthy of Further Investigation 18 Precision Medicine in Obesity Treatment
Fall Obesity Summit Challenges • Complexity of obesity • Insufficient evidence base • Small sample sizes • Lack of standardization (limiting opportunities for combining data and performing meta- analyses) 19 Opportunities • Design clinical trials with intent to address predictors of response (rather than post-hoc) • Innovative trial design (e.g., SMART) • Creation and implementation of clinical decision rules 20 Precision Medicine in Obesity Treatment
Fall Obesity Summit Opportunities • Investigate predictors of response for non- weight outcomes • Prediction of incidence of side effects and adverse events 21 Opportunities • Standardization – Study design – Common measures and techniques (NIH- sponsored ADOPT project) 22 Precision Medicine in Obesity Treatment
Fall Obesity Summit ADOPT Core Constructs and Measures 23 MacLean PS et al. Obesity 2018 ADOPT Core Constructs and Measures 24 MacLean PS et al. Obesity 2018 Precision Medicine in Obesity Treatment
Fall Obesity Summit NIH-Sponsored Workshop Pediatrics • Convened multidisciplinary group of experts to review the current state of the science and identify: – what is known regarding the epidemiology and biopsychosocial determinants of severe obesity in adolescents – what is known regarding effectiveness of treatments for severe obesity in adolescents and predictors of response – gaps and opportunities for future research to develop more effective and targeted treatments for adolescents with severe obesity 25 Summary/Key Points • A large amount of variability exists in obesity treatment outcomes • The sources of heterogeneity are likely multi-factorial and complex • The field of precision obesity medicine is in its infancy (a long way to go with exciting times ahead!) 26 Precision Medicine in Obesity Treatment
Fall Obesity Summit Summary/Key Points • There are many areas worthy of investigation but we need to improve standardization and design future clinical trials with precision medicine in mind 27 Final Thought… • Despite efforts to advance the field of precision obesity medicine, we must acknowledge that multi-faceted treatment approaches will be required to help most patients achieve meaningful and durable outcomes. 28 Precision Medicine in Obesity Treatment
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