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Strategies to Provide Individualized Treatment in Moderate-to-Severe

Atopic Dermatitis

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Meet the Faculty

Amy S. Paller, MS, MD

  • Chair, Department of Dermatology
  • Director, Northwestern University Skin Disease Research Center
  • Walter J. Hamlin Professor of Dermatology
  • Professor of Dermatology and Pediatrics
  • Feinberg School of Medicine
  • Northwestern University
  • Chicago, Illinois

Amy S. Paller, MS, MD, is the Chair and Walter J. Hamlin Professor in the Department of Dermatology in the Feinberg School of Medicine at Northwestern University. She is also the Director of the Northwestern University Skin Disease Research Center and a Professor of Pediatrics.

Dr. Paller is board certified in pediatrics, dermatology, and pediatric dermatology. She holds a medical degree from Stanford University School of Medicine, and a master of science degree in genetics from Brown University. Dr. Paller completed her internship and residencies in pediatrics and dermatology at Northwestern University, and her fellowship in dermatology at the University of North Carolina School of Medicine.

Dr. Paller has been a leader of several international, national, and local societies, among them as President of the Society for Investigative Dermatology (SID), the Society for Pediatric Dermatology, the International Eczema Council, and currently the International Society for Pediatric Dermatology. She has been the recipient of numerous honors, among them the Stephen Rothman Award of the SID, the Clarence Livingood Award of the American Academy of Dermatology, and the Wilma Bergfeld, MD Visioning and Leadership Award from the Women's Dermatological Society. A National Institutes of Health-funded investigator, she currently serves on the Council for the National Institute for Arthritis, Musculoskeletal and Skin Diseases. Dr. Paller serves on multiple editorial and advisory boards, and is both an editorial and grant reviewer. Dr. Paller has published almost 600 research articles, book chapters, and other contributions to the scientific literature. Her clinical and research interests include atopic dermatitis, psoriasis, genetic skin problems, diabetic ulcers, and nanotechnology approaches for topically-delivered gene therapy.

Jonathan M. Spergel, MD, PhD

  • Professor of Pediatrics
  • Chief, Allergy Section
  • Stuart E. Starr Endowed Chair of Pediatrics
  • Director, Center for Pediatric Eosinophilic Disease
  • Director, FARE Center of Excellence
  • The Children's Hospital of Philadelphia
  • Perelman School of Medicine
  • University of Pennsylvania
  • Philadelphia, Pennsylvania

Jonathan M. Spergel, MD, PhD, is a Professor of Pediatrics, Chief of the Allergy Section, and Stuart E. Starr Endowed Chair of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania. He is also the Director of the Center for Pediatric Eosinophilic Disease and the Director of the Food Allergy Research Education Center of Excellence at The Children's Hospital of Philadelphia.

Dr. Spergel is board certified in pediatrics, allergy, and immunology. He holds a medical degree and doctor of philosophy degree in biomedical sciences from Mount Sinai School of Medicine. Dr. Spergel completed his internship and residency in pediatrics at Yale-New Haven Hospital, and his fellowship in allergy and immunology at Children's Hospital in Boston.

Dr. Spergel has been named a Top Doctor by Castle Connolly and a Top Doc with National Distinction by US News and World Report for several years. He is a fellow of the American College of Allergy, Asthma, and Immunology and the American Academy of Allergy, Asthma, and Immunology, and has held multiple leadership positions with both groups. Dr. Spergel is also a fellow of the American Academy of Pediatrics and belongs to several other national and local societies. He serves on the editorial boards of multiple scientific journals, and has published over 100 peer-reviewed research publications. His clinical and research interests include asthma, atopic dermatitis, allergic rhinitis, and food allergy.

Learning Objectives

  • Utilize updated criteria and guidelines to accurately diagnose atopic dermatitis (AD) and assess severity
  • Describe the limitations of currently available therapies in addressing underlying AD pathophysiology
  • Evaluate recent clinical evidence on the utility of approved and emerging biologic agents to address the underlying pathophysiology of AD
  • Discuss strategies that will improve patient satisfaction with treatment and reduce the burden of comorbidities

Disease Overview

  • Cycle of itching and scratching
  • Cellular damage and secondary infections
  • Eczematous lesions associated with Th2 and Th22 inflammation
  • Dry skin due to epidermal barrier dysfunction

Th, T helper cell.

Burden of AD

Unmet Needs in AD

Diagnostic Evaluation

Diagnostic Criteria for AD

  • Diagnosis of exclusion based on clinical presentation
  • Biomarkers not yet specific enough to confirm diagnosis or assess severity
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  • Pruritus
  • Eczema (acute, subacute, chronic)
  • Morphology: typical or atypical?
  • Age-specific patterns
    • Infants and children: facial, neck, extensor involvement
    • Any age: current or previous flexural lesions; sparing of groin and axillary regions
  • History: chronic or relapsing
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  • Early age of onset
  • Atopy
  • Personal and/or family history
  • IgE reactivity
  • Xerosis
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  • Scabies
  • Seborrheic dermatitis
  • Contact dermatitis (allergic or irritant)
  • Cutaneous T-cell lymphoma
  • Psoriasis
  • Photosensitivity dermatoses
  • Cutaneous toxicity
  • Erythroderma of other causes

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Testing Recommendations

IgE, immunoglobin E.

Pathophysiology of AD

Epidermal Barrier Breakdown: A Vicious Cycle

  • Dysregulation in Th2, Th22, and Th17 cytokines
  • Dysregulation in Th2, Th22, and Th17 cytokines
  • IL-4/IL-13/IL-31/IL-22
  • Dysregulation in Th2, Th22, and Th17 cytokines
  • IL-4/IL-13/IL-31/IL-22
  • Inflammatory cascade

IL, interleukin.

Treatment Approach

AAD Guideline Series Published in (2014)*

Diagnosis and Assessmenta
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  • Diagnostic and exclusionary features
  • Biomarkers
  • Disease severity
  • Clinical outcomes assessment
  • Common associations and comorbidities
  • Risk factors for disease
Topical Therapyb
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  • Nonpharmacologic interventions
  • Corticosteroids
  • Calcineurin inhibitors
  • Antimicrobials and antiseptics
  • Antihistamines
  • Other topical agents
Phototherapy and Systemic Agentsc
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  • Phototherapy
  • Immunomodulatory agents
  • Antimicrobials
  • Antihistamines
Disease Flares and Adjunctive Therapyd
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  • Preventing flares
  • Educational interventions
  • Allergic disease and allergy testing
  • Dietary interventions
  • Environmental modifications
  • Other topical agents

*Guidelines PDFs available free at www.aad.org.

AAD, American Academy of Dermatology.

Traditional Therapeutic Options

Mild AD

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Moderate-to-Severe AD

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New and Emerging Therapeutic Options

Biologic Agent: Dupilumab

  • 1.IL-4Rα antagonist blocks IL-4 and IL-13 signaling pathways
  • 2.Approved as second-line treatment for moderate-to-severe AD after topical treatments
  • 3.Subcutaneous injection approved for patients 18 years old
  • 4.Granted accelerated FDA approval March 2017 Approved by European Commission September 2017

mAb, monoclonal antibody.

New and Emerging Therapeutic Options

Biologic and Small-molecule Drugs in Development for Moderate-to-Severe AD

Agents Inhibitor Class Trial Phase Route Patients in Trials (N)
Biologic Agents
Bermekima (MABp1) IL-17α 2 SC 1 recruiting trial (29)
Etokimab (ANB020) IL-33 2 IV 1 recruiting trial (300)
GBR-830* OX40 2 SC 1 recruiting trial (392)
Lebrikizumab (TNX-650) IL-13 2 SC 1 recruiting trial (275)
MOR-106* IL-17C 2 IV 1 recruiting trial (180)
Nemolizumab (CIM 331) IL-31RA 2 SC 1 active trial (351)
Tralokinumab (CAT-354) IL-13 3 SC 5 active/recruiting trials (3,348)
Small-molecule Agents
Abrocitinib (PF-04965842) JAK 1 3 oral 4 active/recruiting trials (4,420)
Baricitinib (LY3009104) JAK 1/2 3 oral 6 active/recruiting trials (3,950)
Upadacitinib (ABT-494) JAK 1 3 oral 4 active/recruiting trials (2,596)

*Generic names not available upon activity launch.

IV, intravenous; JAK, Janus kinase; OX40, tumor necrosis factor receptor superfamily member 4; RA, receptor antagonist; SC, subcutaneous.

Comorbidities

More than Skin Deep: AD Comorbidities

AD patients at increased risk for developing a variety of allergic comorbidities

  • Allergic rhinitis, asthma, conjunctivitis, food allergies, eosinophilic esophagitis

6 endotypes associated with higher risk of developing comorbidity

  • Early onset, persistence, atopic parent(s), severity, filaggrin mutation, polysensitization

Several other comorbidities

  • Infections (Staphylococcus aureus, eczema herpeticum)
  • Neuropsychiatric (ADHD, depression, anxiety, autism, suicidal ideation)
  • Emerging (cardiometabolic disease, autoimmune disease)

Patient Adherence

Treatment Adherence

  • Nonadherence pervasive in AD, especially for long-term treatment

Summary

  • AD is an inflammatory disease involving immune dysregulation and epidermal barrier breakdown
  • Disease negatively affects QOL and leads to multiple comorbidities
  • Diagnosis of exclusion based on clinical presentation
  • Multiple treatments available depending on disease severity
  • Systemic immunosuppression not suitable for long-term maintenance
  • Dupilumab the only biologic currently available
    • Trials show long-term efficacy
    • Careful documentation needed for coverage
  • Several biologic and small-molecule agents now in development