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Description: Faculty David I. Bernstein, MD Professor of Medicine and Environmental Health Division of Immunology, Allergy and Rheumatology University of Cincinnati College of Medicine Cincinnati, Ohio Amy S. Paller, MD Walter J. Hamlin Professor and

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slide2. Faculty David I. Bernstein, MD
Professor of Medicine and Environmental Health
Division of Immunology, Allergy and Rheumatology
University of Cincinnati College of Medicine
Cincinnati, Ohio Amy S. Paller, MD
Walter J. Hamlin Professor and Chair of Dermatology
Professor of Pediatrics
Northwestern University Feinberg School of Medicine
Chicago, Illinois<br>
slide3. Program Overview Video 1. Epidemiology
Video 2. Pathophysiology
Video 3. Clinical Assessment
Video 4. Medical Management: Overview
Video 5. Medical Management 1
Video 6. Medical Management 2
Video 7. Prevention of Flares
Video 8. Emerging Therapies<br>
slide4. Learning Objectives After participating in this program, the participant will be able to:
Examine the epidemiology and pathogenesis of AD and the relevance to the management of patients with AD .
Integrate a proactive approach to long-term disease management in AD, with a focus on prevention of flares, assessment of disease activity, and patient education.
Discuss the mechanisms, efficacy, and safety data for emerging biologic therapies and which patients are likely to benefit.<br>
slide5. Epidemiology Video 1<br>
slide6. Atopic Dermatitis: Definition Chronic, pruritic, eczematous skin disease1,2
Often associated with elevated serum IgE levels and a personal or family history of type I allergies, allergic rhinitis, and asthma
Atopic dermatitis = atopic eczema1
Atopic dermatitis ≠ eczema
ICD codes for atopic dermatitis and eczema are different 1. Eichenfield LF, et al. J Am Acad Dermatol. 2014;70(2):338-351.
2. Whiteley J, et al. Curr Med Res Opin. 2016;doi:10.1080/03007995.2016.1195733.<br>
slide7. Case Scenario: Emily HPI: Emily is being seen for her 6-month well-child visit
Red cheeks with edema and exudation
Emily has dry skin with generalized itching, sometimes making it difficult for her to fall asleep
Medications: none
Allergies: dairy products aggravate skin itching and rash
FH: father and mother with seasonal allergic rhinitis
PE: skin – facial eczema, xerosis of face, as well extensor surfaces of joints<br>
slide8. Atopic Dermatitis: Epidemiology Occurs most frequently in children, but also affects adults1,2
Up to 25% of children
Up to 7% of adults
Prevalence higher in women than men2,3
Onset commonly between ages of 3 and 6 months1,2
60% by age 1 year
85% to 90% by age 5 years 1. Eichenfield LF, et al. J Am Acad Dermatol. 2014;70(2):338-351.
2. Guttman-Yassky E, et al. J Allergy Clin Immunol. 2011;127(5):1110-1118.
3. Whiteley J, et al. Curr Med Res Opin. 2016;doi:10.1080/03007995.2016.1195733.<br>
slide9. Atopic Dermatitis: Epidemiology (cont) Severity1
In children
Mild (two-thirds), moderate (one-quarter); severe (<10%)
Percentage of people with severe AD increases with age
Pooled analysis of 45 studies (N=110,651) showed2
Children who developed AD by age 2 y had less persistent disease
80% of children with AD had disease resolution by 8 years after diagnosis, >95% by 20 years after diagnosis
Later age of onset and greater severity  more persistent AD 1. Chernyshov PV, et al. Clin Cosmet Investig Dermatol. 2016;9:159-166.
2. Kim JP, et al. J Am Acad Dermatol. 2016;75(4):681-687.<br>
slide10. Atopic Dermatitis: Epidemiology (cont) Study of infants (age 3-18 mos) with recent onset AD (≤3 mos) showed many developed an allergic condition over 3 years
Asthma (10.7%)
Allergic rhinitis (22.4%)
Food allergy (15.9%)
Allergic conjunctivitis (14.1%)
≥1 atopic comorbidity (37.0%) Schneider L, et al. Pediatr Dermatol. 2016;33(4):388-398.<br>
slide11. Atopic Dermatitis: Epidemiology (cont) Impact on children varies over time
0-3 years: parental exhaustion, emotional distress  impaired mother-child attachment
3-10 years: teasing, bullying, avoid social interactions and sports
10 years to adulthood: low self-esteem Chernyshov PV, et al. Clin Cosmet Investig Dermatol. 2016;9:159-166.<br>
slide12. Pathophysiology Video 2<br>
slide13. Immune triggers stimulate the release of inflammatory mediators Peng W, et al. Clin Exper Allergy. 2015;45:566-574. Pathogenic Mechanisms in Acute Atopic Dermatitis<br>
slide14. Pathophysiology Complex interplay of 3 factors
Barrier dysfunction
Immunological
Environmental Egawa G, et al. Cogent Biol. 2015;1;1103459.<br>
slide15. Disease Biomarkers Are Needed Biomarkers are being identified to1,2:
Facilitate diagnosis
Assess disease severity
Identify AD disease phenotypes  targeted therapy
Predict individual responses to medications 1. Mansouri Y, et al. J Clin Med. 2015;4:858-87.
2. Thijs JL, et al. J Clin Med. 2015:4:479-487.<br>
slide16. Clinical Assessment Video 3<br>
slide17. Case Scenario: Jack Jack is a 13-year-old male, accompanied by his mother.
During the visit, he is noted to frequently scratch the flexural areas of his arms.
History: Jack has complained of dry, itchy skin on his arms for many years that worsened over the past 2 years. Symptoms are worse in the winter.
Mother had asthma and father has seasonal allergies
Jack has asthma since 4 years of age
PE:
Dry skin
Erythema, dryness, lichenification noted in flexural areas of both arms
Hyperlinear palms and increased scaling on legs
Mom also shows hyperlinear palms/dry legs Image courtesy of DermNetNZ.org under the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 (http://creativecommons.org/licenses/by-nc-nd/3.0/nz/) with no changes.<br>
slide18. Patient Assessment in Routine Clinical Practice Not recommended in practice
Disease severity measurement scales*
Quality of life measurement scales Recommended as part of PE
General questions
Itch
Impact on daily activity, sleep
Disease persistence
Associated conditions
Rhinitis/Rhinoconjunctivitis
Asthma
Food allergy
Sleep disturbance
Depression *Not recommended outside of a clinical trial. US Food and Drug Administration requires Investigator Global Assessment that is used for product labeling. Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.<br>
slide19. Risk Factors Strong association
Family history of atopy
Odds of developing atopic dermatitis

Both parents are atopic: 3 to 5-fold higher risk
Loss of function mutations in the FLG gene (minority – 10% or less)
Earlier onset
More severe, persistent disease
Eczema herpeticum Moderate association
African-American race
Higher parental education
Unclear association
Pet exposure
Urban living
Daycare Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.
Kelleher et al. JACI 2015;135:930-935.<br>
slide20. Transepidermal Water Loss at 2 Days of Life as a Predictor of Atopic Dermatitis Kelleher M, et al. J Allergy Clin Immunol. 2015;135(4):930-935. *Patients were grouped by percentiles based on history of parental atopy and transepidermal water loss test reading score at 2 days. TEWL threshold scores were 5.0 gwater/m2/h (25th percentile), 7.0 gwater/m2/h (50th percentile), and 9.0 gwater/m2/h (75th percentile).
†1597 infants screened. At 6 months, 18.7% were diagnosed with AD. At 12 months, 15.5% were diagnosed with AD N=1903 infants† Interpretation:
Infants in top quartile at 2 days are 7.1 times more likely to be diagnosed with AD at 1 year.<br>
slide21. Diagnostic Features Essential Features
Pruritus
Eczematous dermatitis (acute, subacute, chronic)
Typical morphology and age-specific patterns
Facial, neck, and extensor involvement in infants and children
Current or previous flexural lesions at any age
Sparing of the groin and axillary regions
Chronic or relapsing history Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.<br>
slide22. Diagnostic Features (cont) Important Features (seen in most)
Early age of onset
Atopy
Personal and/or family history
IgE reactivity
Xerosis Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.<br>
slide23. Distribution<br>
slide24. Atopic Dermatitis: Differential Diagnosis Other eczematous disorders
Contact dermatitis
Seborrheic dermatitis
Dyshidrotic eczema
Hand eczema
Nummular dermatitis
Psoriasis
Scabies Unusual disorders
Ichthyoses
Immune deficiency diseases
Photosensitivity dermatoses
Erythroderma of other causes
Cutaneous T-cell lymphoma Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.<br>
slide25. Role of the Laboratory Laboratory testing not needed for most patients1
IgE level not elevated in 5% to 37%2,3
Numerous biomarkers, but none are reliable to distinguish atopic dermatitis from other inflammatory diseases4,5
Allergen skin testing helpful in those with
Respiratory allergies (allergic rhinitis or asthma)
Food allergies: screening – will only suggest food sensitization 1. Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.
2. Ott H, et al. Acta Derm Venereol. 2009;89(3):257-261.
3. Folster-Holst, et al. Allergy. 2006;61(5):629-632.
4. Thijs J, et al. Curr Opin Allergy Clin Immunol. 2015;15(5):453-460.
5. Mansouri Y, et al. J Clin Med. 2015;4:858-87.<br>
slide26. Medical Management: Overview Video 4<br>
slide27. Case Scenario: Wynonna Wynonna is a 7-year-old female diagnosed at age 9 months with AD primarily involving her forearms and lower legs
Current meds: emollients 1-2 x/day + low-potency TCS
Upon questioning, Wynonna reports that her pruritus has not improved, and is sometimes unbearable when she plays soccer. She also says it is sometimes difficult to fall asleep
PE: moderate erythema with numerous excoriations noted on trunk, arms and legs but no sign of infection<br>
slide28. Goals of Therapy Reduce the number and severity of flares
Reduce pruritus and improve quality of life
Maintain normal activities of daily living
Maximize disease-free periods
Prevent infectious complications
Avoid/Minimize side effects of therapy Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
Lyons JJ, et al. Immunol Allergy Clin North Am. 2015;35(1):161-183.<br>
slide29. Overview of Atopic Dermatitis Management TCI, topical calcineurin inhibitor; TCS, topical corticosteroid Modified from Eichenfield LF, et al. Pediatrics. 2015;136(3):554-565. Basic Management
 Skin Care
-Moisturizers
-Warm bath/shower
 Trigger Avoidance Mild Disease Acute Treatment
Low-potency TCS 2x/d applied to inflamed skin<br>
slide30. Overview of Atopic Dermatitis Management (cont) TCI, topical calcineurin inhibitor; TCS, topical corticosteroid Modified from Eichenfield LF, et al. Pediatrics. 2015;136(3):554-565. Basic Management
 Skin Care
-Moisturizers
-Warm bath/shower
 Trigger Avoidance Maintenance TCI Maintenance TCS Mild Disease Moderate-to-Severe Disease For relapsing course (frequent/persistent flares despite treatment)
TCS applied at first signs/symptoms or to flare-prone areas Acute Treatment
Low-potency TCS 2x/d applied to inflamed skin Acute Treatment
 Medium-potency TCS applied to inflamed skin
 Consider 2° infection; treat with antibiotic if present
-Introduce dilute bleach baths 2-7x/wk as maintenance Consider
 Nonadherence
 Misdiagnosis
 Referral Flare not resolved within 7 days<br>
slide31. Medical Management I Video 5<br>
slide32. Skin Hydration Bathing followed by immediate application of emollient
Emollient
Use generously - no danger from “excess use”
Lotions vs creams vs oils vs ointments Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.<br>
slide33. Skin Hydration (cont) Bathing followed by immediate application of emollient
Emollient
Use generously - no danger from “excess use”
Lotions vs creams vs oils vs ointments
General recommendations are:
Warm (not hot) water
Bath better than shower
5-10 minutes
Neutral/low pH, hypoallergenic, fragrance-free non-soap cleansers preferred Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.<br>
slide34. Skin Hydration (cont) Bathing followed by immediate application of emollient
Emollient
Use generously - no danger from “excess use”
Lotions vs creams vs oils vs ointments
General recommendations are:
Warm (not hot) water
Bath better than shower
5-10 minutes
Neutral/low pH, hypoallergenic, fragrance-free non-soap cleansers preferred
Bleach baths now standard of maintenance care for pediatric moderate-to-severe AD Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.<br>
slide35. Topical Corticosteroids (TCS) Recommended if symptoms are not controlled by moisturizers alone
Low-potency
Maintenance therapy to prevent exacerbations
Intermediate- and high-potency (halogenated)
Exacerbations for short period or proactive therapy Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.<br>
slide36. Topical Corticosteroids (TCS) (cont) Recommended if symptoms are not controlled by moisturizers alone
Low-potency
Maintenance therapy to prevent exacerbations
Intermediate- and high-potency (halogenated)
Exacerbations for short period or proactive therapy
Ultra-high-potency
No more than 1-2 weeks
Non-facial, non-skinfold areas
Potent, fluorinated corticosteroids should not be used on mucous membranes, face, eyelids, genitalia, and intertriginous areas or in young infants beyond a few days Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.<br>
slide37. Topical Corticosteroids (TCS) (cont) Twice-daily application needed for most until signs and symptoms improve
For frequent, repeated outbreaks at the same site, maintenance “proactive” therapy with intermediate-potency TCS 2-3x/wk may be beneficial Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.<br>
slide38. Topical Corticosteroids (TCS) (cont) Twice-daily application needed for most until signs and symptoms improve
For frequent, repeated outbreaks at the same site, maintenance “proactive” therapy with intermediate-potency TCS 2-3x/wk may be beneficial
Adverse effects of TCS
Local- striae, skin atrophy, periorbital dermatitis, rosacea, allergic contact dermatitis
Systemic
Dependent on skin surface area involved, skin thickness, use of occlusive dressing, duration of use, potency
Risk of adrenal suppression greatest in infants and small children Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.<br>
slide39. Topical Calcineurin Inhibitors (TCI) Pimecrolimus cream 1%; tacrolimus 0.03% and 0.1% ointment
Block production of proinflammatory cytokines and other inflammatory mediators1,2
Advantages vs. TCS2
For face, anogenital, skin folds, or other sensitive areas
No atrophogenic properties; can reverse steroid-induced atrophy
Steroid-sparing: reduce overall TCS when used for maintenance 1. Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
2. Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.<br>
slide40. Topical Calcineurin Inhibitors (TCI) (cont) 2-3x/wk “proactive” application effective in preventing recurrence1,2
Local adverse effects such as stinging and burning are most common1,2 and primarily occur when applied to acutely inflamed lesions
Increased risk of malignancy not observed3, but black box warning for theoretical risk persists and requires reassurance when prescribed 1. Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
2. Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.
3. Siegfried EC, et al. BMC Pediatr. 2016;16:75.<br>
slide41. Other Topical Options Crisaborole: Topical phosphodiesterase-4 (PDE4) inhibitor approved in December 2016 for mild-to-moderate AD in children age ≥2 y<br>
slide42. Other Topical Options (cont) Crisaborole: Topical phosphodiesterase-4 (PDE4) inhibitor approved in December 2016 for mild-to-moderate AD in children age ≥2 y
Tar preparations1,2
No randomized trials have demonstrated efficacy
Should not be used on acutely inflamed skin
Tar shampoo may be beneficial 1. Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
2. Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.<br>
slide43. Other Topical Options (cont) Crisaborole: Topical phosphodiesterase-4 (PDE4) inhibitor approved in December 2016 for mild-to-moderate AD in children age ≥2 y
Tar preparations1,2
No randomized trials have demonstrated efficacy
Should not be used on acutely inflamed skin
Tar shampoo may be beneficial
Topical antihistamines1,2
Not recommended because of lack of evidence supporting efficacy, risk of absorption and of contact dermatitis
Even oral anthistamines are only used in AD for their soporific effects or for associated allergic disorders (nonsedating antihistamines) 1. Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
2. Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.<br>
slide44. Other Topical Options (cont) Crisaborole: Topical phosphodiesterase-4 (PDE4) inhibitor approved in December 2016 for mild-to-moderate AD in children age ≥2 y
Tar preparations1,2
No randomized trials have demonstrated efficacy
Should not be used on acutely inflamed skin
Tar shampoo may be beneficial
Topical antihistamines1,2
Not recommended because of lack of evidence supporting efficacy, risk of absorption and of contact dermatitis
Even oral anthistamines are only used in AD for their soporific effects or for associated allergic disorders (nonsedating antihistamines)
Topical antimicrobials2
Not recommended because of lack of efficacy, risk of contact dermatitis
Exception: antiseptic dilute bleach baths3-5 1. Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
2. Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.
3. Hon KL, et al. J Dermatolog Treat. 2016;27(2):156-162.
4. Wong SM, et al. J Dermatol. 2013;40(11):874-880.
5. Huang JT, et al. Pediatrics. 2009;123:e808-e814.<br>
slide45. Additional Considerations Identify and eliminate triggering factors
Avoidance of common irritants – soaps/detergents/wool/occlusive fabrics
Potential contact allergens, such as fragrance, preservatives, botanicals
Recommend control of temperature and humidity
Consider possible allergy triggers (other than foods) with skin tests, although skin tests (and allergy patch tests) are poorly predictive of triggering factors
Allergen immunotherapy
Selected patients with aeroallergen sensitivity – may worsen AD Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.<br>
slide46. Additional Considerations (cont) Identify and eliminate triggering factors
Avoidance of common irritants – soaps/detergents/wool/occlusive fabrics
Potential contact allergens, such as fragrance, preservatives, botanicals
Recommend control of temperature and humidity
Consider possible allergy triggers (other than foods) with skin tests, although skin tests (and allergy patch tests) are poorly predictive of triggering factors
Allergen immunotherapy
Selected patients with aeroallergen sensitivity – may worsen AD
Limited data regarding the benefits of leukotriene inhibitors (shown to be ineffective for AD) Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.<br>
slide47. Additional Considerations (cont) Patient and family education
Chronic nature of disease, exacerbating factors, efficacy and safety of treatments
Demonstrate skin care techniques
Provide written treatment plan
Refer to other healthcare providers as needed
Advise of patient support organizations Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.<br>
slide48. Additional Considerations (cont) Patient and family education
Chronic nature of disease, exacerbating factors, efficacy and safety of treatments
Demonstrate skin care techniques
Provide written treatment plan
Refer to other healthcare providers as needed
Advise of patient support organizations
Patient and family quality of life often impaired
Additional treatment may be needed for itching, behavioral disorders, and sleep disturbances Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.<br>
slide49. Medical Management II Video 6<br>
slide50. Difficult-to-Treat Patients with Atopic Dermatitis Phototherapy
Narrowband UVB most commonly used due to low risk profile, relative efficacy, availability, clinician experience
Incidence of adverse events considered to be low
Most common are actinic damage, local erythema/tenderness, pruritus, burning, stinging
Rarely used because of poor accessibility and often poorly tolerated, especially for acute AD
Home phototherapy a consideration for patients with poor adherence Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.
Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.<br>
slide51. Difficult-to-Treat Patients with Atopic Dermatitis (cont) Systemic agents
Lack of comparative trial data makes it difficult to determine the relative efficacy and safety of available options
Most commonly used in US are
Cyclosporine, methotrexate, mycophenolate mofetil
Corticosteroids
Should be avoided if possible due to side effects, risk for abuse
Reserved for acute, severe exacerbations as a short-term bridge to other systemic, non-steroid therapy in adults; no role in children Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.
Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.<br>
slide52. Difficult-to-Treat Patients with Atopic Dermatitis (cont) Systemic agents (cont)
Antimicrobials1
Recommended only in patients with clinical evidence of bacterial evidence
Antihistamines1
Sedating ones may be beneficial in the setting of sleep loss secondary to pruritus 1. Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.<br>
slide53. Difficult-to-Treat Patients with Atopic Dermatitis (cont) Systemic agents (cont)
Antimicrobials1
Recommended only in patients with clinical evidence of bacterial evidence
Antihistamines1
Sedating ones may be beneficial in the setting of sleep loss secondary to pruritus
Other interventions that have not been proven to work and are not supported in treatment guidelines
Primrose oil, omega-3, vitamin D, aromatherapy
Probiotics/Synbiotics2,3
Limited data suggest benefit of synbiotics (combination of prebiotics and probiotics) but not probiotics
Highly dependent on strains, doses 1. Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.
2. Rather IA, et al. Front Microbiol. 2016;7:507.
3. Chang YS, et al. JAMA Pediatr. 2016;170(3):236-242.<br>
slide54. Prevention of Flares Video 7<br>
slide55. Case Scenario: Juan Juan is a child seen for continuing care of atopic dermatitis
History
Diagnosed 3 years ago with atopic dermatitis at age 11 months
Achieves good symptom relief with basic measures (bathing, moisturizers, control of triggers)
However, experiences frequent flares which cause him to scratch intensely  developed secondary skin infection<br>
slide56. Prevention of Flares Preventing or at least increasing the time interval between flares is a critical goal of management
Important to act quickly in treating a flare1 1. Wollenberg A, et al. JEADV. 2016;30:729-747. TCI, topical calcineurin inhibitor; TCS, topical corticosteroid<br>
slide57. Prevention of Flares (cont) Preventing or at least increasing the time interval between flares is a critical goal of management
Important to act quickly in treating a flare1
Two approaches (with continued basic management)2,3, 4 1. Wollenberg A, et al. JEADV. 2016;30:729-747.
2. Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.
3. Eichenfield LF, et al. Pediatrics. 2015;136(3):554-565.
4. Schmitt J, et al. Br J Dermatol. 2011;164(2):415-428. TCI, topical calcineurin inhibitor; TCS, topical corticosteroid<br>
slide58. Prevention of Flares (cont) Preventing or at least increasing the time interval between flares is a critical goal of management
Important to act quickly in treating a flare1
Two approaches (with continued basic management)2,3, 4

Antiseptic/Antibiotic therapy
Topical- dilute bleach bath (minimally twice-weekly; severe may require daily)
Systemic- S. aureus most common pathogen; MSSA >> MRSA
Oral cephalosporin; amoxicillin/clavulanate 1. Wollenberg A, et al. JEADV. 2016;30:729-747.
2. Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.
3. Eichenfield LF, et al. Pediatrics. 2015;136(3):554-565.
4. Schmitt J, et al. Br J Dermatol. 2011;164(2):415-428. TCI, topical calcineurin inhibitor; TCS, topical corticosteroid<br>
slide59. Prevention of Flares (cont) Patient/Family education1,2
Promote adherence to maintenance therapy
Written action plan
Multidisciplinary teaching3
Dermatological, nutritional, psychological components
Psychological support is particularly important in those with emotional triggers or experiencing significant distress
Nutritional education particularly important in children with food allergies 1. Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.
2. Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
3. Spielman SC, et al. J Clin Med. 2015;4:1156-1170.<br>
slide60. Prevention of Flares (cont) Control trigger factors: more important for associated allergic disorders1,2
Hard to demonstrate that allergic triggers play a role in AD
Young children- food allergies (probably <10% and especially in severely affected children with AD)
Older children and adults- environmental aeroallergens 1. Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.
2. Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.<br>
slide61. Emerging Therapies Video 8<br>
slide62. Crisaborole: New Topical for Mild-to-Moderate AD Overview
Phosphodiesterase-4 inhibitor  ↑ cAMP  ↓ release of pro-inflammatory cytokines
Approved by FDA December 2016

Phase 3 trials
2 randomized, double-blind, vehicle-controlled trials
Patients
Age ≥2 years with diagnosed atopic dermatitis, ≥5% treatable body surface area, IGSA score of 2 or 3
Excluded: biologic therapy or systemic corticosteroids within 28 days, TCS/TCI within 14 days
Treatment
Ointment applied twice daily to each lesion (except scalp) for 28 days Paller AS, et al. J Am Acad Dermatol. 2016;75(3):494-503. IGSA, Investigator’s Static Global Assessment score; TCI, topical calcineurin inhibitor; TCS, topical corticosteroid<br>
slide63. Crisaborole: Results of 2 Phase 3 Trials Paller AS, et al. J Am Acad Dermatol. 2016;75(3):494-503. P=.005 Trial AD-301: Crisaborole (n=503), vehicle (n=256); Trial AD-302: crisaborole (n=513), vehicle (n=250) P<.001 % of Patients with ISGA of Clear (0) or Almost Clear (1) at Day 29<br>
slide64. Crisaborole: Results of 2 Phase 3 Trials (cont) Paller AS, et al. J Am Acad Dermatol. 2016;75(3):494-503. P<.001 P<.001 P<.001 P<.001 P=.008 Trial AD-301: Crisaborole (n=503), vehicle (n=256); Trial AD-302: crisaborole (n=513), vehicle (n=250) % of Patients with Improvement in AD Signs at Day 29<br>
slide65. Case Scenario: Tamika Tamika is a 32-year-old female diagnosed with severe AD at age 23 years
She has been treated with intensive topical therapy as well as systemic medications, and has either developed adverse effects or not responded (cyclosporine; mycophenolate mofetil; methotrexate)
Preventive therapy with twice-weekly topical corticosteroid therapy has yielded limited benefit
She continues to experience impaired quality of life, including poor sleep, which has made it difficult for her as a school teacher<br>
slide66. Dupilumab Fully human monoclonal antibody that blocks IL-4-receptor-  blocks actions of the Th-2 cytokines IL-4 and IL-13

Subcutaneous injection Peng W, et al. Clin Exper Allergy. 2015;45:566-574.<br>
slide67. Patients: Adults with moderate-to-severe AD with inadequate response to topical treatment

Randomized (1:1:1:1:1:1) to 16 weeks of treatment with:
Dupilumab 300 mg every week
Dupilumab 300 mg every 2 weeks
Dupilumab 200 mg every 2 weeks
Dupilumab 300 mg every 4 weeks
Dupilumab 100 mg every 4 weeks or
Placebo every week Thaci D, et al. Lancet. 2016;387(10013):40-52. Dupilumab: Phase 2b Trial<br>
slide68. Dupilumab: Phase 2b Trial Results Thaci D, et al. Lancet. 2016;387(10013):40-52. N=379
P<0.0001 dupilumab (all doses) vs placebo<br>
slide69. Results:
Improvements in EASI score were significantly greater at all doses of dupilumab vs placebo
Treatment-emergent adverse event in 81% (dupilumab) and 80% (placebo)
Nasopharyngitis: 28% (dupilumab) vs 26% (placebo) Thaci D, et al. Lancet. 2016;387(10013):40-52. Dupilumab: Phase 2b Trial Results (cont)<br>
slide70. Dupilumab: Phase 3 Trials (SOLO 1 and SOLO 2) 2 Separate phase 3, double-blind, parallel-group clinical trials
SOLO 1 and SOLO 2
Adults with chronic moderate-to-severe AD inadequately controlled by topical treatment or for whom topical treatment was inadvisable
Investigator Global Assessment score 3 or 4
IGA determines severity of AD and clinical response to treatment [range 0 (clear) to 4 (severe)] Simpson EL, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1610020.<br>
slide71. Dupilumab: Phase 3 Trials (cont) Randomized to:
Dupilumab 300 mg every week
Dupilumab 300 mg every other week or
Placebo
Moisturizers bid for ≥7 d before randomization, then throughout trial
Topical or systemic rescue treatment allowed
If systemic rescue treatment  patient discontinued (categorized as no response) Simpson EL, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1610020.<br>
slide72. Dupilumab: Phase 3 Trials Results Simpson EL, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1610020. *Reduction from baseline of ≥2 points on the IGA at week 16. P<.001 for all comparisons between dupilumab and placebo<br>
slide73. Dupilumab: Phase 3 Trials Results (cont) Simpson EL, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1610020. *Improvement from baseline of at least 75% on the Eczema Area and Severity Index (EASI) at week 16. P<.001 for all comparisons between dupilumab and placebo<br>
slide74. Dupilumab: Phase 3 Trials Results (cont) Significantly greater improvement with dupilumab vs placebo regarding
Pruritus
Sleep
Symptoms of anxiety or depression
Quality of life

Fewer patients treated with dupilumab used rescue medication (19% vs 52%) Simpson EL, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1610020.<br>
slide75. Dupilumab: Phase 3 Trials Results (cont) Simpson EL, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1610020.<br>
slide76. Pro-inflammatory Targets Interleukins
IL-4 receptor-
IL-5
IL-12/IL-23 p40
IL-13
IL-22
IL-31
IL-31 receptor Janus kinase inhibitor
Thymic stromal lymphopoietin
H4-receptor blocker
Liver X receptor agonist<br>