Pediatric Atopic Dermatitis: Assessing Disease Burden and Treatment

Case Scenario #1
• Luis is a 9-year-old male seen in clinic with a complaint of worsening
pruritus causing difficulties in school and sleep.
• History: He first complained of dry, itchy skin on the flexural areas of his
arms and legs about 2 years ago. Symptoms are worse in winter.
– Father has asthma and perennial rhinitis
• Physical examination
– Dry skin
– Erythema, dryness, lichenification noted in flexural
areas of both arms and legs
– Increased scaling on legs noted
© Professor Raimo Suhonen. Used by DermNet New Zealand with permission under the Creative Commons Attribution-NonCommercial-
NoDerivs 3.0 (http://creativecommons.org/licenses/by-nc-nd/3.0/nz/) with no changes.

Wide Ranging Impact of Atopic Dermatitis
AD
Severe AD in childhood
disrupted education
Sleep disturbance and
daytime
fatigue due to itch and
pain
Headaches,
depression,
low self-esteem
Poor tolerance for
heat—causes flares
of AD
Poor qualifications,
limited career prospects,
financial problems
Not able to work
in a full-time job
Potential
suicidal ideation
Family holidays
in warm climates
impossible; limits
business trips

Itch and Sleep Symptoms
2 2.1 2.7
10%
0.4
5.9 5.8 5.7
80%
2.6
0
10
20
30
40
50
60
70
80
Mean PO-SCORAD Pruritus VAS Mean Pruritus NRS Mean Itch Frequency (d/wk) Mean % with Itch All Day Mean Number of Nights with Sleep
Disturbed Over Past Week
Adults with Atopic Dermatitis at 6 US Academic Medical Centers (N=1519)
Mild (n=689) Moderate/Severe (n=830)
Simpson E, et al. JAMA Dermatol. 2018;154(8):903-912.
NRS, numerical rating scale; PO-SCORAD, Patient-Oriented Scoring of Atopic Dermatitis

Cumulative Impact On Patients’ Lives Resulting In Life
Impairment*
8.3
2.8 0.7 2
24.3
41.3
20.6
5.5
18.9
36.7
0
20
40
60
80
100
A lot/Very much influenced
clothes worn
A lot/Very much affected
social/leisure activities
A lot affected work/studying A lot/Very much interfered with
shopping, home, garden activities
Family income <$50,000/y
Percent
of
Patients
Adults with Atopic Dermatitis at 6 US Academic Medical Centers (N=1519)
Mild (n=689) Moderate/Severe (n=830)
Simpson E, et al. JAMA Dermatol. 2018;154(8):903-912.
*Based on the Dermatology Life Quality Index

Impairment is Worse with AD Than Psoriasis
Eckert L, et al. J Am Acad Dermatol. 2018;78(1):54-61.
Data derived from the 2013 US National Health and Wellness Survey, a real-world survey of adults with and without a self-reported diagnosis of AD in the US
AD self-reports were propensity matched with non-AD controls and with psoriasis controls.
Work Productivity and Activity Impairment, US
0%
5%
10%
15%
20%
25%
30%
35%
40%
Absenteeism
(P<0.001)
Presenteeism
(P=0.027)
Overall work
impairment
(P=0.004)
Activity
impairment
(P<0.001)
Mean
%
impairment
AD No AD
0%
5%
10%
15%
20%
25%
30%
35%
Absenteeism
(P=0.168)
Presenteeism
(P=0.428)
Overall work
impairment
(P=0.572)
Activity
impairment
(P=0.855)
Mean
%
impairment
AD Psoriasis

Recommendations for Assessing Disease Severity
• Commonly assessed based on
– Body surface area
– Location, distribution
• Other tools are available but not commonly used in practice
– EASI, POEM, SCORAD
– DLQI
• Best practice: Combine clinical tools with patient interview questions to
assess impact of AD on daily functioning and quality of life
Charman CR, et al. Arch Dermatol. 2004;140(12):1513-1519.
Eichenfield LF, et al. J Am Acad Dermatol. 2014;70(2):338-351.
Rehal B, et al. PLoS One. 2011;6(4):e17520.
Finlay AY, et al. Clin Exp Dermatol. 1994;19(3):210-216.
DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; POEM, Patient-Oriented Eczema Measure; SCORAD, Scoring Atopic Dermatitis
It is critical to fully understand the impact of AD from the
patient’s perspective

Assessing the Burden of Atopic Dermatitis in Clinical Practice
AAD guidelines recommend that clinicians ask general questions about itch,
sleep, impact on daily activity, and disease persistence
• How long have you had your AD?
• Is your AD active in bursts or tends to be active all the time?
• Could you tell me how AD has affected you emotionally?
• Could you tell me how AD has affected your sleep?
• Could you tell me how AD has affected you at school or work?
• Could you tell me how AD has affected your social life?
• What are your goals for treatment of AD?
• Could you tell me about the side effects that you have experienced from treatment for
your AD, or that you are concerned about?
AAD, American Academy of Dermatology

Associated Comorbidities
• Other atopic diseases
• Neuropsychiatric
• Cardiovascular diseases
• Others
– Osteoporosis
– Injuries
– Developmental issues
– Infections
Silverberg JI. Clin Dermatol. 2017;35:360-366.

Association of Pediatric and Adult Atopic Dermatitis with
Comorbid Atopic Disease
Silverberg JI, et al. Pediatr Allergy Immunol. 2013;24(5):476-486.
National Health Interview Survey 2012 (n=34,500 adults ages 18-85 years).
11.7
7.2
9.9
3.2
25.5
18.7
28.4
13.2
0.0
10.0
20.0
30.0
40.0
Ever asthma Current asthma Respiratory
allergy
Food allergy
No atopic dermatitis Atopic dermatitis
National Survey of Children’s Health 2007-2008 (n=91,642 children).
Percent
of
Persons
Percent
of
Persons

Atopic Dermatitis and Mental Health
Group Odds Ratio 95% CI
Adults/Children with vs without
AD
1.71 1.48-1.98
Adults with vs without AD 2.08 1.70-2.55
Children with vs without AD 1.31 0.99-1.75
Adults/Children with moderate-
severe AD vs without AD
1.81 1.40-2.35
Adults/Children with mild AD vs
without AD
1.28 0.41-4.06
CI, confidence interval
Patel KR, et al. J Am Acad Dermatol. 2019;80(2):402-410.
Depression is more common in persons
with vs without AD
Suicidal ideation is more common in
persons with vs without AD
Group Odds Ratio 95% CI
Adults/Children with vs without
AD
1.97 1.19-3.25
Adults with vs without AD 2.87 1.89-4.36

Atopic Dermatitis and Cardiovascular Comorbidities
Atopic
Dermatitis
Obesity
CV risk
Behavioral
Factors
CV
Events
Kantor R, et al. J Am Acad Dermatol. 2016;75(6):1119-1125. Silverberg JI, et al. J Investig Dermatol. 2016;136(8):1714-1716. Silverberg
JI. J Allergy Clin Immunol. 2016;137(3):938-940. Silverberg JI. J Allergy Clin Immunol. 2015;136(3):824-825. Silverberg JI, et al. J Allergy
Clin Immunol. 2015; 135(3): 721-728. Silverberg JI, et al. JAMA Dermatol. 2015 1;151(2):144-152. Andersen YM, et al. J Allergy Clin
Immunol. 2016;138(1):310-312. Su VY, et al. Ann Med. 2014;46(2):84-89.
CAD
Angina
MI
Stroke
PVD
Hypertension
Dyslipidemia
Prediabetes
T2 Diabetes

Atopic Dermatitis and Osteoporosis/Osteopenia
• Analysis of
– 2006-2012 NEDS
– 2002-2012 NIS
• Total number of encounters
(age ≥50 y)
– NEDS: 61,065,660
– NIS: 44,425,777
1.31
1.86
1.37
1.84
1.25
0.86
1.24
1.02
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2
Osteoporosis Osteopenia Osteoporosis Osteopenia
Adjusted
Odds
Ratio
Association of AD with Osteoporosis & Osteopenia
NEDS NIS
Age ≥70 y
Age ≥50 y
NEDS, National Emergency Department Sample; NIS, Nationwide Inpatient Sample
Shaheen MS, et al. J Am Acad Dermatol. 2019;80(2):550-551.

Atopic Dermatitis and Risk of Infection
Infection Odds
Ratio
95%
Confidence
Interval
Ear infection 1.29 1.16-1.43
Strep throat 2.31 1.66-3.22
Urinary tract infection 2.31 1.66-3.22
Pneumonia 1.72 0.75-3.98
Serrano L, et al. J Am Acad Dermatol. 2018;doi: 10.1016/j.jaad.2018.11.028.

Risk Factors
• Family history of atopy
• If both parents are atopic  3- to 5-fold higher risk
• Loss of function mutations in FLG gene (minority – ≤10%)
• Earlier onset; more severe, persistent disease; eczema herpeticum
Strong
Association
• African American race
• Higher parental education
Moderate
Association
• Pet exposure
• Urban living
• Daycare
Unclear
Association
Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.
Kelleher et al. J Allergy Clin Immunol. 2015;135:930-935.

Atopic Dermatitis Is a Complicated Disease
https://en.wikipedia.org/wiki/Spongiosis.
http://creativecommons.org/licenses/by-sa/3.0/

Key Cytokine Targets in Atopic Dermatitis
Gandhi NA, et al. Nat Rev Drug Discov. 2016;15(1):35-50.

Immunologic Pathways
Vakharia PP, et al. BioDrugs. 2017;31:409-422.

Immunologic Targets in Atopic Dermatitis: Th2 Pathway

Selected
Treatment
Targets

Goals of Therapy
1. Reduce the number and severity of flares
2. Reduce pruritus and improve quality of life
3. Maintain normal activities of daily living
4. Maximize disease-free periods
5. Prevent infectious complications
6. Avoid/Minimize side effects of treatment
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.

Key Recommendations for Basic Management
Recommendation Strength Level
 Moisturizers should be an integral part of treatment since there is strong
evidence that their use can reduce disease severity and the need for
pharmacologic intervention
A I
 Bathing is suggested as part of treatment and maintenance; however,
there is no standard for the frequency or duration of bathing
C III
 Moisturizers should be applied soon after bathing to improve skin
hydration
B II
 Limited use of nonsoap cleansers (that are neutral to low pH,
hypoallergenic, and fragrance free)
C III
 The addition of oils, emollients, and most other additives to bath water
and the use of acidic spring water cannot be recommended
C III

“A” Rated Evidenced-Based Approaches
• For use of moisturizers
• For use of topical corticosteroids
– Consider steroid side effects
• For use of topical calcineurin inhibitors
– Use for steroid sparing
– Use off label in children <2 years
– Use for proactive maintenance
• Against routine use of topical antistaphylococcal treatments
Eichenfield L, et al. J Am Acad Dermatol. 2014;71:116-132.

Skin Hydration
• 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

Trigger Avoidance
• 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)

Patient Education Regarding Disease State
• 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 health care 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,
mental health disorders, and sleep disturbances

Treatment Overview
Eichenfield LF, et al. Pediatrics. 2015;136(3):554-565.

Patient Adherence to Atopic Dermatitis Treatment
Is Poor
Krejci-Manwaring J, et al. J Am Acad Dermatol. 2007;56(2):211-216.
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 7 14 21 28 35 42 49 56 63
Adherence
Rates
Days
Mean Average Daily Adherence
Mems Cap Adherence Linear Moving Average

Why Are Patients Non-Adherent?
Poor motivation The patient may not be particularly bothered
Secondary gain Seeking disability or other gain
Lack of trust in doctor Physician-patient relationship is the foundation
Fear of medication Founded or unfounded fear of treatment
Don’t know what to do Patients may not remember oral instructions
Burden of treatment Sometimes the treatment is worse than the disease!
Perceived burden Sometimes treatment seems worse than the disease
Passing the responsibility buck With multiple caregivers, no one may take
responsibility
Forgetfulness “Pavlov’s dog” problem
Laziness No energy to follow treatment
Resignation Some patients have just given up

Advanced: Psychological Techniques
1. Employing anchoring techniques
2. Recognizing probability bias
3. Providing salient descriptions
4. Understanding loss aversion
5. Framing risks of adverse effects
6. Using adverse effects to advantage
7. Rewarding and praising children
Basics: Complexity, Cost, and
Instructions
1. Reduce treatment burden
2. Written instructions
3. Triggers
4. Steroid phobia
Foundation: Trust and
Accountability
1. The physician-
patient relationship
2. Follow-up
Adherence Intervention Pyramid
Lewis DJ, Feldman SR. Practical Ways to Improve Patient Adherence, 2017.

Reminders Are Not The Same As Accountability
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1 2 3 4 5 6 7 8 9 10 11 12
Percent
Weekly
Adherence
Weeks from Baseline
Mean Weekly Adherence to Once Daily Topical Adapalene 0.1% Gel
Control Frequent Visits Electronic Reminders Parental Reminders
Yentzer B, et al. J Am Acad Dermatol. 2011;64:793-795.

Specific Strategies to Promote Adherence
• Build trust
• Simplify treatment
• Use combination products when
appropriate
• “This is the treatment that most
children/teenagers use for this
condition”
• Prescribe only “all natural”
treatments
• Provide a written action plan
• Provide your cell phone number
• Frequent follow-up visits,
particularly after treatment is
initiated or changed
• Provide positive reinforcement
• Ask what difficulty they may be
having with treatment

Case Scenario #2
• Anita is a 6-year-old female diagnosed at age 11 months with AD
primarily involving her forearms and lower legs
• Current treatmentDaily bathing followed by emollients 1-2 x/day
– Dilute bleach bath once or twice weekly
• Upon questioning, Anita reports that her pruritus has not improved,
and is sometimes unbearable when she plays outdoors. She also says it
is sometimes difficult to fall asleep
• PE: moderate erythema with numerous excoriations noted on neck,
arms, and legs; no sign of infection

Topical Corticosteroids
• Use when nonpharmacologic interventions have failed
• Effective for both active inflammation and disease prophylaxis
– Acute treatment of active inflammation: intermediate-/high-potency
– Prophylaxis: low-potency
• Frequency
– Acute inflammation: twice-daily application generally used
– Proactive maintenance: once- or twice-weekly to commonly flaring areas
Eichenfield LF, et al. J Allergy Clin Immunol. 2017;139:S49-S57.

Topical Corticosteroids (cont)
• Quantity- fingertip unit per area equivalent to 2 palms
• Caution- areas of thin skin
• Adverse effects
– Local: acneiform or rosacea-like eruptions, focal hypertrichosis, purpura,
atrophy, striae, telangiectasia
– Systemic- rare

Topical Calcineurin Inhibitors
• Non-steroidal therapy for acute flares and maintenance therapy in
adults and children age >2 y
– May use in combination with topical corticosteroid initially for acute
inflammation
• Steroid-sparing option for sensitive or thin skin

Topical Calcineurin Inhibitors (cont)
• Frequency
– Acute inflammation- twice-daily application
– Proactive maintenance- twice-/thrice-weekly
• Adverse effects
– Local: burning, stinging, pruritus
– Systemic- rare; no need for routine blood monitoring
• Patient education about boxed warning

Crisaborole: Results of 2 Phase 3 Studies
32.8% 31.4%
25.4%
18.0%
0%
20%
40%
60%
80%
100%
AD-301 AD-302
%
of
Patients
with
ISGA
of
Clear
(0)
or
Almost
Clear
(1)
at
Day
29
Crisaborole Vehicle
59%
40%
60%
55%
52%
40%
30%
48% 48%
41%
0%
20%
40%
60%
80%
100%
Erythema Exudation Excoriation Induration/
Papulation
Lichenification
%
of
Patients
with
Improvement
in
AD
Signs
at
Day
29
Paller AS, et al. J Am Acad Dermatol. 2016;75(3):494-503.
P=.038
P<.001
P<.001
P<.001
P<.001
P<.001
P=.008
AD-301: Crisaborole (n=503), vehicle (n=256); AD-302: crisaborole (n=513), vehicle (n=250)

Crisaborole Safety
Adverse Event* Crisaborole
(n=1012)
Vehicle
(n=499)
P
Treatment-related burning and stinging 4.4% 1.2% 0.001
Infections and infestations 11.7 11.8 –
Gastrointestinal disorders 2.7 2.4 –
Respiratory, thoracic, and mediastinal
disorders
4.6 3.0 –
Application site pain 4.4 1.2 0.001
Skin and subcutaneous tissue disorders 3.7 4.2 –
Nervous system disorders 1.4 0.4 –
Paller AS, et al. J Am Acad Dermatol. 2016;75(3):494-503.
*Treatment-emergent adverse evens (≥1% of patients)

Wet Wrap Therapy
• Concomitant use with topical corticosteroid (but not topical
calcineurin inhibitor) for recalcitrant atopic dermatitis
• Caution about overuse due to folliculitis, skin maceration,
secondary infections

Others
Possibly effective (?)
• Bleach bath1
– Appears to be no more effective than
water in reducing AD severity2
– Proactive use for patients with
recurrent skin infections
• However, concern of widespread
antimicrobial resistance
– Concomitant use of intranasal
mupirocin
Not recommended
• Topical antihistamines
– Not recommended due to risk of
absorption and development of
photoallergic contact dermatitis1
1. Eichenfield LF, et al. J Allergy Clin Immunol. 2017;139:S49-S57.
2. Chopra R, et al. Ann Allergy Asthma Immunol. 2017;119;435-440.

Optimization of Topical Care: My Anecdotal Experience
• Topical treatments can be extraordinarily effective
• Adherence is crucial
– Keep treatment as simple as possible
– Higher potency steroid given less frequently may be
appropriate
• Reinforce best practices at each visit

Case Scenario #3
• Phil is a 20-year-old male with a 4-year history of atopic dermatitis. He
is being referred by his primary care physician for worsening symptoms.
– Although he has done his best to identify and minimize triggers, his atopic
dermatitis has worsened since he began attending college and living in a dormitory
• He is diagnosed with moderate atopic dermatitis
– IGA 3 with 12% of his body surface area affected
• Current treatment:
– Daily bathing
– Twice-daily moisturizer
– Twice-daily crisaborole

Selected
Treatment
Targets
Stop 7.2

Systemic Immunosuppressants
• Recommended for severe atopic dermatitis refractory to topical
regimens and phototherapy or when QOL is severely affected
• Cyclosporine, methotrexate, mycophenolate mofetil, azathioprine more
effective than interferon- and oral calcineurin inhibitors
• No specific recommendations regarding optimal dosing and duration
• Adverse effects- close monitoring is recommended

Systemic Corticosteroids
• Avoid if possible, particularly in children
– Short-term use of acute inflammation
• Possible role as bridge therapy to another systemic, steroid-sparing
treatment

Dupilumab*: Phase 3 Trials (SOLO 1 and SOLO 2)
10% 8%
38% 36%
37% 36%
0%
20%
40%
60%
80%
100%
SOLO 1 SOLO 2
%
of
Patients
with
Qualifying
IGA
Score
at
Week
16
Primary Endpoint†
Placebo QW
Dupilumab 300 mg QOW
Dupilumab 300 mg QW
15%
12%
51%
44%
52%
48%
0%
20%
40%
60%
80%
100%
SOLO 1 SOLO 2
%
of
Patients
with
EASI75
at
Week
16
Secondary Endpoint§
*Approved dose is an initial dose of 600 mg followed by 300 mg every other week
†Reduction from baseline of ≥2 points on the IGA at week 16.
§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
Simpson EL, et al. N Engl J Med. 2016;375(24):2335-2348.

Dupilumab: Phase 3 Trials (SOLO 1 and SOLO 2) (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%

Dupilumab*: Phase 3 Trials (SOLO 1 and SOLO 2) (cont)
Adverse Event, % SOLO1 SOLO 2
Placebo
(n=222)
Dupilumab
QOW
(n=229)
Dupilumab
QW
(n=218)
Placebo
(n=234)
Dupilumab
QOW
(n=236)
Dupilumab
QW
(n=237)
≥1 AE 65 73 69 72 65 66
≥1 Serious AE 5 3 1 6 2 3
Injection site reaction 6 8 19 6 14 13
AD exacerbation 30 13 10 35 14 16
Headache 6 9 5 5 8 9
Allergic conjunctivitis 1 5 3 1 1 1
Conjunctivitis 1 5 3 <1 4 4
Nasopharyngitis 8 10 11 9 8 8
Non-skin infection 22 30 31 24 25 26
*Approved dose is an initial dose of 600 mg followed by 300 mg every other week

Phototherapy
• Recommended for atopic dermatitis refractory to topical
treatments
• Specific situations
– UVA1- acute exacerbations
– UVB- chronic atopic dermatitis
– UVA with psoralen- severe widespread atopic dermatitis
• Adverse effects
– Local: actinic damage, local erythema and tenderness, altered
pigmentation
– Systemic: infrequent

Other Systemic Therapies
• Antihistamines- consider short-term use of sedating antihistamine for
short-term use for sleep disturbance due to pruritus
• Antimicrobials
– Not routinely recommended
– Consider if evidence of bacterial infection, eczema herpeticum
• Vitamin D- consider if low level or poor intake
• Others- limited/no evidence

Selected Phase 2/3 Investigational Agents
Class/Target(s) Agent(s)
Janus kinase inhibitors Baricitinib Tofacitinib Upadacitinib PF-04965842 Delgocitinib
www.ClinicalTrials.gov
Agents shown in red have published results of a phase 2/3 clinical trial for atopic dermatitis

Selected Phase 2/3 Investigational Agents (cont)
Anti-IL-13 mAb Lebrikizumab Tralokinumab
Anti-IL-17 mAb Secukinumab

Anti-IL-22 mAb Fezakinumab
Anti-IL-31RA mAb Nemolizumab

Anti-IL-22 mAb Fezakinumab
Anti-IL-31RA mAb Nemolizumab
NK-1 receptor
antagonist
Tradipitant
Anti-IgE Ligelizumab Omalizumab MED14212

Baricitinib
• Phase 2, randomized, double-blind,
placebo-controlled trial
• N=124 patients with moderate/severe
AD
• Run-in phase with topical
corticosteroids x 4 weeks
• Randomized to 16 weeks of treatment
with:
– Baricitinib 2 mg once daily
– Baricitinib 4 mg once daily
– Placebo once daily
• Results
– EASI-50: baricitinib 4 mg (61%) vs
placebo (37%)
• Significant difference seen at week 4
– Pruritus and sleep loss also improved
with baricitinib
– Treatment-emergent adverse event
• Baricitinib 2 mg (46%)
• Baricitinib 4 mg (71%)
• Placebo (49%)
Guttman-Yassky E, et al. J Am Acad Dermatol. 2018;doi:10.1016/jaad.2018.01.018.

Tofacitinib
• Phase 2a randomized, double-blind, vehicle-controlled study
• N=69 adults with mild/moderate AD
• Randomized to 4 weeks of treatment with
– Tofacitinib 2% twice daily
– Vehicle twice daily
• Treatment-emergent AE: tofacitinib (31%); vehicle (56%)
Bissonnette R, et al. Br J Dermatol. 2016;175:902-911.
Mean Percentage Change in EASI Total Score Proportion Achieving PGA of 0/1 plus ≥2-point
Improvement from Baseline
*P<0.05; **P<0.001; ***P<0.0001

Upadacitinib
• Phase 2b randomized, double-blind, placebo-controlled study
• N=67 adults with moderate/severe AD
• Randomized (1:1:1:1) to 16 weeks of treatment with
– Upadacitinib 7.5 mg, 15 mg, or 30 mg once daily
– Placebo
• At week 16
– Patients treated with upadacitinib were rerandomized to continue upadacitinib or
switched to placebo once daily
– Patients treated with placebo were rerandomized to continue placebo or switched
to upadacitinib 30 mg once daily
• At week 20, rescue upadacitinib 30 mg once daily provided at first
instance of EASI 50
https://www.prnewswire.com/news-releases/abbvie-presents-upadacitinib-longer-term-32-week-and-patient-reported-outcomes-data-
from-phase-2b-atopic-dermatitis-study-at-27th-european-academy-of-dermatology-and-venereology-eadv-congress-300711938.html
EASI, Eczema Area and Severity Index

Upadacitinib (cont)
-34.0%
-48.0%* -44.0%*
-69.0%**
-100%
-80%
-60%
-40%
-20%
0%
Placebo
Upadacitinib 7.5
mg
Upadacitinib 15
mg
Upadacitinib 30
mg
Mean Percentage Change from Baseline in the
EASI Score at Week 32
*P<0.05
**P<0.01
EASI, Eczema Area and Severity Index
Itch was rated from 0 (no itch) to 10 (worst imaginable)
https://www.prnewswire.com/news-releases/abbvie-presents-upadacitinib-longer-term-32-week-and-patient-reported-outcomes-data-from-phase-
2b-atopic-dermatitis-study-at-27th-european-academy-of-dermatology-and-venereology-eadv-congress-300711938.html
-6%
53%**
44%**
61%***
-20%
0%
20%
40%
60%
80%
100%
Placebo Upadacitinib 7.5
mg
Upadacitinib 15
mg
Upadacitinib 30
mg
Mean Percentage Improvement from Baseline in
Pruritus/Itch Numerical Rating Scale at Week 32
**P<0.01
***P<0.001
● EASI 90 at 16 weeks was achieved by 10%, 14%, 26%, and 50% (placebo; upadacitinib 7.5 mg, 15 mg, 30 mg, respectively)
● Improvement in patient-reported outcomes (pain, sleep)
● 2 serious adverse events (infection, non-melanoma skin cancer) in placebo/upadacitinib 30 mg group

PF-04965842
6.3% 8.2% 12.3%
27.8%*
44.5%**
0%
20%
40%
60%
80%
100%
Placebo PF-04965842
10 mg
PF-04965842
30 mg
PF-04965842
100 mg
PF-04965842
200 mg
Participants (%) Achieving IGA 0 or 1 and ≥2
Points Improvement from Baseline at Week 12
*P=0.0184
**P=0.0032
-35.2% -31.1%
-40.7%
-59.0%*
-82.6%**
-100%
-80%
-60%
-40%
-20%
0%
Placebo
PF-04965842
10 mg
PF-04965842
30 mg
PF-04965842
100 mg
PF-04965842
200 mg
Percentage Change from Baseline in the EASI
Score at Week 12
*P=0.0091
**P<0.0001
AE, adverse event; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment
ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/results/NCT02780167?term=pf-04965842&cond=Atopic+Dermatitis&rank=1
• Phase 2 randomized, double-blind, placebo-controlled study
• N=269 adults with moderate/severe AD
• Randomized to 12 weeks of treatment with:
– PF-04965842 10 mg, 30 mg, 100 mg, or 200 mg QD
– Placebo QD
• Viral upper respiratory tract infection most common AE: PF-04965842 (10.2-17.9%); placebo (8.9%)

Nemolizumab: XCIMA Trial
• Phase 2, randomized, double-blind,
placebo-controlled trial
• N=264 patients with moderate/severe AD
inadequately controlled with topical
treatment
• Randomized to 12 weeks of treatment
with:
– Nemolizumab 0.1 mg/kg Q4 wks
– Nemolizumab 0.5 mg/kg Q4 wks
– Nemolizumab 2 mg/kg Q4 wks
– Placebo Q4 wks
– Nemolizumab 2 mg/kg Q8 wks
• Nasopharyngitis most common AE:
nemolizumab (10-17%); placebo (15%)
Ruzicka T, et al. N Engl J Med. 2017;376(9):826-835.
Change from Baseline in Pruritus Score at Week 12
AE, adverse event

Omalizumab
• A meta-analysis and systematic review found no concrete evidence
demonstrating effectiveness of omalizumab for AD1
• Severe adverse effects may limit its use in AD2
– Anaphylaxis, cardiovascular, and cerebrovascular events
• It remains to be determined if omalizumab is effective in subgroups
of patients with AD1
1. Wang HH, et al. J Allergy Clin Immunol. 2016;138:1719-1722.
2. Wang D, et al. Am J Clin Dermatol. 2016;17:425-443.

Pediatric Atopic Dermatitis: Assessing Disease Burden and Treatment

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