Precision Medicine in Obesity Aaron S. Kelly, Ph.D. Associate - - PDF document

Fall Obesity Summit Precision Medicine in Obesity Treatment

1 obesitymedicine.org

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

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• Describe the heterogeneity of response to

various obesity treatments

• Identify factors associated with favorable

treatment outcomes

• Characterize the future challenges and
• pportunities regarding precision medicine

approaches for treatment of obesity Objectives

Fall Obesity Summit Precision Medicine in Obesity Treatment

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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

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Heterogeneity - Adult

Lifestyle, Pharmacotherapy, Surgery

MacLean PS et al. Obesity 2018

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Heterogeneity - Pediatric

Lifestyle, Pharmacotherapy, Surgery

Unpublished data 6

Heterogeneity - Pediatric

Kelly AS et al. JAMA Pediatr 2013

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Sources of Heterogeneity

• Genetic
• Physiological
• Behavioral
• Psychosocial
• Environmental
• And more…

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What is Precision Medicine?

• Identification and characterization of sources
• f 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

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Primordial Predictors

Previous Weight Loss Attempts

Carraca EV et al. Obesity Facts 2018 10

Primordial Predictors

Early Weight Loss

Gross AC et al. Unpublished

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Primordial Predictors

Early Weight Loss

Fujioka K et al. Obesity 2016 12

Primordial Predictors

Early Weight Loss

Courcoulas AP et al. JAMA Surg 2018

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Primordial Predictors

Variability in Weight Loss Trajectory

Feig EH et al. Obesity 2017 14

Primordial Predictors

Variability in Weight Loss Trajectory

Marek RJ et al. Obesity 2017

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Primordial Predictors

Self-Report Appetite/Cognitive Restraint

Thomas EA et al. Obesity 2016 16

Primordial Predictors

Sex and Self-Report Appetite

Nathan BM et al. Clin Obes 2016

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Primordial Predictors

Eating Disorder Pathology

Balantekin KN et al. Obesity 2017 18

On the Horizon

Areas Worthy of Further Investigation

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Challenges

• Complexity of obesity
• Insufficient evidence base
• Small sample sizes
• Lack of standardization (limiting opportunities

for combining data and performing meta- analyses)

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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

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Opportunities

• Investigate predictors of response for non-

weight outcomes

• Prediction of incidence of side effects and

adverse events

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Opportunities

• Standardization

– Study design – Common measures and techniques (NIH- sponsored ADOPT project)

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ADOPT

Core Constructs and Measures

MacLean PS et al. Obesity 2018 24

ADOPT

Core Constructs and Measures

MacLean PS et al. Obesity 2018

Fall Obesity Summit Precision Medicine in Obesity Treatment

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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

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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!)

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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

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• Despite efforts to advance the field of precision
• besity medicine, we must acknowledge that

multi-faceted treatment approaches will be required to help most patients achieve meaningful and durable outcomes. Final Thought…