Unmet Needs in AD Care

AD Confers a Substantial Burden on

Patients1,2
Direct skin Indirect effects Mood & lifestyle
effects Shame, Negative effect on
Scratching embarrassment relationships

ITC Open sores

Blood-stained Time lost to daily DEPRESSI
clothing & bedding cleaning ON
H ANXIETY

Disturbed sleep Red, irritated skin Negative self image

Patients with AD
Itch is the most reported Difficulty with Poor school & work have high rates of
bothersome symptom attention, mood performance depression, anxiety,
for patients with AD1
and suicidal ideation2

1. McCleary K. August 13, 2021. Accessed September 13, 2021.

http://www.morethanskindeep-eczema.org/uploads/1/2/5/3/125377765/mtsd_report_-_digital_file.pdf .
2. Patel KR et al. J Am Acad Dermatol. 2019;80(2):402-410.
Differing Perceptions of Disease Burden
Between Patients and Providers
About one-third of patients rate their AD severity
differently from their clinicians
• 1 in 10 patients rated their AD as more severe than their clinicians, while 2 in 10
patients considered their disease to be less severe than their clinicians
• Patients tended to focus more on their skin-related quality of life
• Clinicians tended to focus more on sleep disturbance
• Better patient-clinician communication and incorporation of quality-of-life
measures may be important for management decision making

Wei W et al. Am J Clin Dermatol. 2017;18(6):825-835.

Inadequate Disease Control Is Common in
Patients With AD and Leads to Poor Outcomes1,2
• 59% of patients with AD have Proportion of Patients With DLQI Score >10
inadequate disease control2 (Very Large Quality of Life Effect)1
• Rate of inadequate control increases with
higher severity
• Patients with inadequate control are at
greater risk for:1,2
• Depression and anxiety
• Stress
• Itch interfering with daily activities
• Sleep disturbances interfering with daily
lives
Image courtesy of Simpson EL et al. JAMA Dermatol. 2018;154(8):903-912. CC-BY-NC-ND.

1. Simpson EL et al. JAMA Dermatol. 2018;154(8):903-912.

2. Wei W et al. J Dermatol. 2018;45(2):150-157.
There Is an Unmet Need for New Treatment
Options in AD Inadequate Control by Current Treatment
Regimen
• Many patients with 100

uncontrolled AD are currently 80

60
83.4
receiving standard therapies 65.0

Rate of inadequate control

40 53.4 53.9
20
0
• These data underscore the ra
py
s an
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on
ly
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importance of guideline- ph
oto
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adherent care and new ag
e nto
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Wei W et al. J Dermatol. 2018;45(2):150-157.

Components of Basic AD Care
Tenets of Basic Skin Care for AD
Application of Bathing
moisturizers
• Frequent and liberal use • Should be followed with
• Ideally inexpensive and free of moisturizer use
additives, fragrances, perfumes, or • Use of fragrance-free,
other sensitizers hypoallergenic nonsoap cleansers
with neutral or low pH
• Bleach baths for those with
moderate or severe AD and signs
of secondary bacterial infection

Eichenfield et al. J Am Acad Dermatol. 2014;71(1):116-132.

Topical Moisturizers Applied Frequently Can
Improve AD Inflammation and Symptoms
• Topical moisturizers address dry skin and transepidermal water loss
• Several benefits of moisturizers have been identified in clinical trials
Benefits of Moisturizers

Increased skin Decreased Decreased

hydration erythema lichenification

Decreased Decreased use of

Decreased
fissuring topical
pruritus
corticosteroids

Eichenfield et al. J Am Acad Dermatol. 2014;71(1):116-132.

Topical Corticosteroids Indicated for Relief After
Failure of Good Skin Care and Moisturizers
• Topical corticosteroids (TCS) are the main anti-inflammatory agents
used in adults and children with AD
• Recommended for patients with AD who have not responded to basic
skin care
• Recommendations for use:
• As maintenance on areas that regularly flare (1-2 times per week)
• As treatment for acute flares (daily until lesions are improved for up to 2-3
weeks at a time)

Eichenfield et al. J Am Acad Dermatol. 2014;71(1):116-132.

Adherence to Evidence-Based
Guidelines
 2014 AAD Guidelines Include Recommendations for Acute
and Maintenance Treatment of Mild to Severe AD
Mild Severe
Maintenance

Basic Management Maintenance Topicals

(all patients) • Calcineurin inhibitors (tacrolimus or
• Skin care pimecrolimus) OR
• Antiseptic measures • Medium- and/or low-potency
• Trigger avoidance corticosteroids

Topical Topical
Acute

Low-potency corticosteroids • Medium-potency corticosteroids BID for up to 3 days

BID for up to 3 days beyond beyond clearance
clearance • Oral antibiotic for secondary infection

Eichenfield et al. J Am Acad Dermatol. 2014;71(1):116-132.

Topical Therapies in 2014 AAD Clinical
Guidelines
Topical calcineurin inhibitors
Topical corticosteroids (TCS)
(TCI)
• Recommended for treatment of • Recommended for treatment of itch
active inflammation or itch when bathing, moisturizing, wet-
• May consider low-potency over-the- wrap therapy, and/or TCS have not
counter agents in some cases led to relief
• Carry risk of skin atrophy with long- • Favored over TCS in delicate body
term use areas (eg, face, groin)
• No risk of atrophy but transient
burning after application is common

Eichenfield et al. J Am Acad Dermatol. 2014;71(1):116-132.

Recommendations for Phototherapy in 2014
AAD Guidelines
• UV light (UVA and/or UVB) can be used for acute flares or
maintenance
• Requires 2 to 5 visits per week
• Typically reserved for patients who have failed TCS and TCI
• May be used in combination with TCS and moisturizers
• Associated with short- and long-term adverse events (AEs), including
itch, acute burns, and increased risk for skin cancer

UV, ultraviolet.

Sidbury R et al. J Am Acad Dermatol. 2014;71(2):327-349.

 Adjunctive Systemic Therapies Included in
2014 AAD Guidelines
Cyclosporine A Azathioprine Methotrexate Mycophenolate
mofetil
Decrease in AD
activity (%) 40%-55% 26%-37% 42%-52% 55%-68%

Time to response 2-6 weeks ≥12 weeks 10-16 weeks 8-12 weeks
Dosage 150-300 mg/day 1-3 mg/kg/day 7.5-25 mg/week 1.0-1.5 g oral BID
• Increased serum Leukopenia • Bone marrow Hematologic changes
creatinine • suppression •
• Increased liver • Genitourinary
Selected AEs • Increased blood enzymes • Increased liver symptoms
pressure GI symptoms enzymes GI symptoms
Infection • GI symptoms •
• •
Pediatric Weight-based dosing (3-6 Dosing (0.2-0.7 Dosing (30-50
Dosing (1-4 mg/kg/day)
considerations mg/kg/day) mg/kg/week) mg/kg/day)

1. Sidbury R et al. J Am Acad Dermatol. 2014;71(2):327-349.

2. Wollenberg A et al. J Eur Acad Dermatol Venereol. 2018;32(5):657-682.
AD Therapies Approved After
2014 AAD Guidelines
Crisaborole: Approved in 2016 for AD
FDA-approved indication
Mild-to-moderate AD in adults and children 3 months or older

Mechanism of action
PDE4 inhibition

Route of administration
Topical

Dosing
Thin layer, twice daily

Safety
Application site pain
PDE4, phosphodiesterase 4.

Crisaborole ointment [prescribing information]. New York, NY; Pfizer: 2020.

 Phase 3 AD-301 & AD-302: Crisaborole in
Mild-to-Moderate AD
ISGA Response Rate Clear or Almost-Clear Rate Early Pruritus Reduction
100 100 100

Percent with improvement in pru-

Percent with ISGA of 0 or 1 at day
Percent achieving success at day

90 90
80 80 P =.005 P <.001 80
70 70
60 63
60 P =.038 P <.001 60 51.7 58 60 61
48.5 50 53

ritusb
50 48
29a

40.6 44

29
40 42
40 32.8 31.4 40
29.7 30
25.4 30 20
20 18.0 20 10
10 0
0 0 Base- Day 8 Day 15 Day 22 Day 29
AD-301 AD-302 AD-301 AD-302 line

Crisaborole Vehicle
a
Success defined as Investigator's Static Global Assessment (ISGA) score of 0 or 1 (clear or almost clear) with at least 2-grade improvement.
bImprovement defined as score of 0 or 1 with ≥1-grade reduction from baseline.

Paller AS et al. J Am Acad Dermatol. 2016;75(3):494-503.e6.

Post Hoc Analysis of AD-301 & AD-302 Suggests
Crisaborole Effectiveness Across AD Severity
Response by Severity Response by Severity
According to Baseline ADSI According to Baseline BSA

Image courtesy of Silverberg JI et al. Acta Derm Venereol. 2020;100(13):adv00170. CC BY-NC 4.0.

Silverberg JI et al. Acta Derm Venereol. 2020;100(13):adv00170.

Post Hoc Analysis of AD-301 & AD-302 Suggests
Crisaborole Effectiveness Across Racial/Ethnic
Groups
Response
by Race

Images courtesy of Callender VD et al. Am J Clin Dermatol. 2019;20(5):711-723. CC BY-NC 4.0.

Callender VD et al. Am J Clin Dermatol. 2019;20(5):711-723.

Phase 4 Open-Label Study: Crisaborole
Effectiveness in Infants Aged 3 to 23 Months
ISGA Response With Crisaborole • Pharmacokinetics of
crisaborole were comparable
with those 2 years or older

• No toxicity related to
propylene glycol (eg, CNS
toxicity, cardiac arrhythmia)

Images courtesy of Schlessinger J et al. Am J Clin Dermatol. 2020;21(2):275-284. CC BY-NC 4.0.

Schlessinger J et al. Am J Clin Dermatol. 2020;21(2):275-284.

Dupilumab: Approved in 2017 for AD
FDA-approved indication
Moderate-to-severe AD inadequately controlled with topical therapies or when those therapies are not
recommended in adults and children 6 years or older

Mechanism of action
IL-4 receptor antagonist
Route of administration
Subcutaneous
Dosing
15-29 kg: 600-mg loading dose followed by 300-mg maintenance dose every 4 weeks;
30-59 kg: 400-mg loading dose followed by 200-mg maintenance dose every 2 weeks;
≥60 kg: 600-mg loading dose followed by 300-mg maintenance dose every 2 weeks
Safety
Injection site reactions Eye pruritus
Conjunctivitis Oral herpes

Dupilumab injection [prescribing information]. Tarrytown, NY; Regeneron: 2021.

 Phase 3 SOLO 1 & SOLO 2: Dupilumab in
Moderate-to-Severe AD
IGA Response Rate EASI-75 Response Rate
100 100
Percent achieving qualifying

90
80 80

Percent with EASI-75

score at week 16a

70

at week 16
60 60
50
40 40
30
20 20
10
0 0
SOLO 1 SOLO 2 SOLO 1 SOLO 2
P <.001 for all comparisons of dupilumab vs placebo
a
Qualifying score defined as Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with at least 2-point improvement.

Simpson EL et al. N Engl J Med. 2016;375(24):2335-2348.

 Post Hoc Analysis of Phase 3 Trials Reveals Early,
Sustained Itch Relief With Dupilumab Treatment
Daily Peak Pruritus Improvement Proportion Achieving ≥3 Point Improvement

— placebo (SOLO pooled) — dupilumab 300 mg every other week (SOLO pooled) — placebo (AD ADOL) — dupilumab 200-300 mg every other week

Images courtesy of Silverberg JI et al. J Am Acad Dermatol. 2020;82(6):1328-1336. CC BY-NC-ND 4.0.

Silverberg JI et al. J Am Acad Dermatol. 2020;82(6):1328-1336.

Post Hoc Analysis of Phase 3 Trials Reveals
Important Clinical Benefits in Patients Without Clear
Skin
Change in EASI Score in Patients With IGA >1 Achievement of EASI-75 in Patients With IGA >1

*P <.001
Images courtesy of Silverberg JI et al. Br J Dermatol. 2019;181(1):80-87. CC BY-NC 4.0.

Silverberg JI et al. Br J Dermatol. 2019;181(1):80-87.

Real-World Data Support the Efficacy of Dupilumab,
With High Rates of Patient Satisfaction
Persistence With Dupilumab
• Real-world study of 1963 adults
receiving dupilumab from
insurance database
• Dupilumab persistence:
• 92% at 6 months
• 77% at 12 months
• Among those who discontinued,
likelihood of re-initiation within 4
months was 79%
Image courtesy of Silverberg JI et al. Ann Allergy Asthma Immunol. 2021;126(1):40-45. CC BY-NC-ND 4.0.

Silverberg JI et al. Ann Allergy Asthma Immunol. 2021;126(1):40-45.

Despite the Approval of Novel Agents, AD
Control Remains Suboptimal
• Cross-sectional survey of 150 clinicians and 749 patients with
moderate-to-severe AD
• In 2018, the inadequate control rate was 42.3%
• Slight improvement since 2014, when the inadequate control rate was 58.7%

“Despite the introduction of novel therapies, the burden and

impact of AD, the degree of patient- and physician-reported
disease severity, and the lack of symptom control is still
substantial.”

Vilsbøll AW et al. Dermatol Ther (Heidelb). 2021;11(2):475-486.

Emerging Therapies: Phase 3
Efficacy & Safety Data
JAK-STAT Inhibitors: Mechanism of Action
in AD
• Many cytokines rely on
downstream JAK-STAT signaling
• IL-4, IL-13, IL-31 (Th2 cytokines)
• IL-2 (Th22 cytokines)
• JAK-STAT inhibition can be pan-JAK
or specific to certain types
• JAK1-specific inhibitors: upadacitinib
and abrocitinib
• JAK1/2-specific inhibitors: ruxolitinib
and baricitinib
Image courtesy of Howell MD et al. Front Immunol. 2019;10:2342. CC BY 4.0.

Howell MD et al. Front Immunol. 2019;10:2342.

 Pooled Data From Phase 3 BREEZE-AD1 &
BREEZE-AD2: Oral Baricitinib Monotherapy1,a
Results From Pooled BREEZE-AD1 and BREEZE-AD2 Trials 2
Baricitinib 1 mg Baricitinib 2 mg Baricitinib 4 mg Placebo
Response at Wk 16
(n = 252) (n = 246) (n = 248) (n = 493)

Yes No Yes No Yes No Yes No Enrolled 1239

Atopic Comorbidity (n = 177) (n = 75) (n = 176) (n = 70) (n = 168) (n = 80) (n = 357) (n = 136) patients in total
EASI-50 response rate, % with moderate-
Monotherapy 20.3* 26.7 29.0† 28.6 32.7† 41.3† 11.5 19.9 to-severe AD
With TCS rescue 45.8 64.0 61.9† 61.4 55.4† 63.8 38.1 51.5 and inadequate
IGA (0, 1, 2) response rate, % response to
Monotherapy 18.6* 21.3 25.0† 20.0 29.8† 32.5‡ 9.8 17.6 TCS1
With TCS rescue 36.2 46.7 48.9† 52.9 50.6† 45.0 31.7 44.1

*P  .01 vs placebo; †P  .001 vs placebo; ‡P  .05.

a. Rescue systemic or topical corticosteroids were allowed at investigator discretion.

1. Simpson EL et al. Br J Dermatol. 2020;183(2):242-255.

2. Wollenberg A et al. J Allergy Clin Immunol. 2020;142(2 supplement);AB190.
Phase 3 BREEZE-AD7: Oral Baricitinib Combined
With Background Topical Corticosteroids
vIGA-AD Score of 0 or 1 EASI-75
Odds of improvement vs placebo at week 16
4 mg: 2.8 (95% CI, 1.4-5.6); P =.004
2 mg: 1.9 (95% CI, 0.9-3.9); P =.08
Enrolled 329
patients with
moderate-to-
severe AD
receiving
background TCS

vIGA-AD, validated Investigator Global Assessment for Atopic Dermatitis.

Images courtesy of Reich K et al. JAMA Dermatol. 2020;156(12):1333-1343. CC-BY-NC-ND.

Reich K et al. JAMA Dermatol. 2020;156(12):1333-1343.

 Phase 3 Measure Up 1 & 2: Oral Upadacitinib Monotherapy in
Adolescents and Adults With Moderate to Severe AD

vIGA-AD Response Rate (Week 16) EASI-75 Response Rate (Week 16)
Enrolled 1683
100 100
90 patients with
Percent achieving vIGA-AD

79.7
80 72.9 80 moderate-to-

Percent with EASI-75

69.6
70
60.1 62 severe AD aged

at week 16
60 60
responsea

52
50 48.1 ≥12 years
38.8
40 40
30
20 16.3 13.3 20 13.3
8.4
10
0 0
Measure Up 1 Measure Up 2 Measure Up 1 Measure Up 2
P ≤.0001 for all comparisons of upadacitinib vs placebo

Guttman-Yassky E et al. Lancet. 2021;397(10290):2151-2168.

 Phase 3 AD Up: Oral Upadacitinib Combined With TCS in
Adolescents and Adults With Moderate to Severe AD

vIGA-AD Response Rate EASI-75 Response Rate

Enrolled 901
100 100
90 patients with
Percent achieving vIGA-AD

80 80 moderate-to-

Percent with EASI-75

70
severe AD aged

at week 16
60 60
responsea

50 ≥12 years
40 40
30
20 20
10
0 0
0 4 8 12 16 0 4 8 12 16
P <.01 for all comparisons of upadacitinib + TCS vs placebo + TCS

a. Defined as a vIGA-AD score of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline

Reich K et al. Lancet. 2021;397(10290):2169-2181.

 Phase 3 Heads Up: Oral Upadacitinib vs Dupilumab
in Adults With Moderate to Severe AD
EASI-75 Response Rate EASI-90 Response Rate

Enrolled 692
patients with
moderate-to-
severe AD
aged ≥18 years

a, P ≤.001; b, P ≤.01; c, P ≤.05

Image courtesy of Blauvelt A et al. JAMA Dermatol. 2021;157(9):1047-1055. CC-BY-NC-ND.

Blauvelt A et al. JAMA Dermatol. 2021;157(9):1047-1055.

 Phase 3 JADE MONO-1: Oral Abrocitinib Monotherapy in
Adolescents and Adults With Moderate-to-Severe AD
IGA Response Rate EASI-75
100 100

Percent with an EASI-75 response

— Abrocitinib 200 mg
Percent with an IGA responsea

80 80 Enrolled 387
— Abrocitinib 100 mg 63%
patients with
60 — Placebo 60
moderate-to-
44% 40% severe AD
40 40
aged ≥12
24%
20 20 12%
years
8%
0 0
0 2 4 8 12 0 2 4 8 12
Study week Study week

a. Response defined as an Investigator Global Assessment response 0 or 1 (clear or almost clear) with a ≥2-grade improvement from baseline
 Phase 3 JADE MONO-2: Oral Abrocitinib Monotherapy in
Adolescents and Adults With Moderate-to-Severe AD
IGA Response Rate EASI-75 Response Rate

Enrolled 391
patients with
moderate-to-
severe AD
aged ≥12
years

a, P <.05 vs placebo; b, P <.001 vs placebo.

Images courtesy of Silverberg JI et al. JAMA Dermatol. 2020;156(8):863-873. CC-BY-NC-ND.

Silverberg JI et al. JAMA Dermatol. 2020;156(8):863-873.

Phase 3 JADE COMPARE: Abrocitinib vs
Dupilumab in Adults With Moderate-to-Severe AD
Abrocitinib, 200 mg Abrocitinib, 100 mg Dupilumab, 300 mg Placebo (n = 131)
(n = 226) (n = 238) every other week (n = 242)
Primary end points
IGA response (week 12), % 48.4 36.6 36.5 14.0
Difference from placebo 34.8 (P <.001) 23.1 (P <.001) 22.5 NA
EASI-75 (week 12), % 70.3 58.7 58.1 27.1
Difference from placebo 43.2 (P <.001) 31.9 (P <.001) 30.9 NA
Secondary end points
Itch response (week 2), % 49.1 31.8 26.4 13.8
Difference from placebo 34.9 (P <.001) 17.9 (P <.001) 12.5 NA
Difference from dupilumab 22.1 (P <.001) 5.2 (P =.20) NA NA
IGA response (week 16), % 47.5 34.8 38.8 12.9
Difference from placebo 35.0 (P <.001) 22.1 (P <.001) 25.6 NA
Difference from dupilumab 9.4 -3.5 NA NA
EASI-75 response (week 16), % 71.0 60.3 65.5 30.6
Difference from placebo 40.4 (P <.001) 29.7 (P <.001) 34.7 NA
Difference from dupilumab 5.5 -5.1 NA NA

Bieber T et al. N Engl J Med. 2021;384(12):1101-1112.

Oral JAK-STAT Inhibitor Safety
Considerations
• In patients with AD, the most common AEs with JAK
inhibitors include:1
• Nasopharyngitis
Black Box
• Upper respiratory tract infection Warnings for Oral
• Herpes zoster reactivation JAK Inhibitors2
• Nausea • Thrombosis
• Diarrhea • Malignancy
• JAK inhibitors already approved for use in • Serious infections
rheumatoid arthritis have been associated with rare
but serious AEs, resulting in FDA black box
warnings1,2
1. Tsai HR et al. J Pers Med. 2021;11(4):279.
2. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain
chronic inflammatory conditions. September 1, 2021. Accessed September 11, 2021.
https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-cl
ots-and-death
.
 Phase 3 TRuE-AD1 & TruE-AD2: Ruxolitinib Cream vs
Vehicle for the Treatment of Adults and Adolescents With AD
Enrolled 1249 patients
IGA Response Rate (Week 8) EASI-75 Response Rate (Week 8) with AD aged ≥12 years
100 100 who had IGA of 2/3 and
Odds of success vs placebo at week 8
90 BSA of 3%-20%
0.75%: 6.4 (95% CI, 3.6-11.9)
Percent achieving IGA re-

80 1.5%: 7.5 (95% CI, 4.2-14.0) 80

Percent with EASI-75

70 Application-site

at week 16
60 60 reactions were reported
sponsea

50 in 1.5% of patients
40 40
30 Longer-term studies are
20 20 needed, but low
10 bioavailability of topical
0 0 ruxolitinib may reduce
TRuE-AD1 TRuE-AD2 TRuE-AD1 TRuE-AD2 safety issuesb
P <.0001 for all comparisons of ruxolitinib vs vehicle
a
Response defined as Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with at least 2-point improvement.
b
The 44-week safety extension study has been completed, but results are not yet published.

Papp K et al. J Am Acad Dermatol. 2021;85(4):863-872.

IL-13 Antagonists: Mechanism of Action in
AD
• AD lesions have overexpression
of Th2 cytokines, including IL-13
• IL-13 triggers several
pathophysiologic mechanisms
of AD:
• Inflammatory itch
• Disruption of skin barrier integrity
• Skin microbiome dysbiosis

Image courtesy of Howell MD et al. Front Immunol. 2019;10:2342. CC BY 4.0.

Howell MD et al. Front Immunol. 2019;10:2342.

 Phase 3 ECZTRA 1 and ECZTRA 2: Tralokinumab
Monotherapy vs Placebo in Adults With Moderate-to-
Severe AD
Enrolled 1596 patients with AD aged ≥18 years with moderate-to-severe AD
ECZTRA 1 (IGA 0 or 1) ECZTRA 2 (IGA 0 or 1) ECZTRA 1 (EASI-75) ECZTRA 2 (EASI-75)

Upper respiratory tract infection and conjunctivitis were more frequent with tralokinumab than with placebo

*P <.05; **P <.01; *** P <.001; †P =.002.
Images courtesy of Wollenberg A et al. Br J Dermatol. 2021;184(3):437-449. CC BY-NC-ND 4.0.

Wollenberg A et al. Br J Dermatol. 2021;184(3):437-449.

Phase 3 ECZTRA 3: Tralokinumab With
Background TCS vs Placebo With Background TCS
IGA Score 0 or 1 EASI-75
Enrolled 380
patients with AD
aged ≥18 years
who had
moderate-to-
severe AD

*P <05; **P <.01; ***P <.001; model-based treatment difference: †P <.05; ‡P <.001.

Images courtesy of Silverberg JI et al. Br J Dermatol. 2021;184(3):450-463. CC BY-NC-ND 4.0.

Silverberg JI et al. Br J Dermatol. 2021;184(3):450-463.

Phase 2b Trial: Lebrikizumab vs Placebo in
Adults With Moderate-to-Severe AD1
IGA 0/1 Response Rate EASI-75 Response Rate Enrolled 280 patients with
AD aged ≥18 years who had
moderate-to-severe AD
Treatment-emergent AEs included
upper respiratory tract infection,
injection site reactions,
herpesvirus infections, and
conjunctivitis

Phase 3 trials of lebrikizumab

monotherapy (ADvocate 1 and
ADvocate 2) met all primary and
key secondary endpoints; full
a. P <.01; b, P <.05; c, P <.001.
results expected in 20222
Images courtesy of Guttman-Yassky E et al. JAMA Dermatol. 2020;156(4):411-420. CC-BY-NC-ND.

1. Guttman-Yassky E et al. JAMA Dermatol. 2020;156(4):411-420.

2. Lilly's lebrikizumab significantly improved skin clearance and itch in people with moderate-to-severe atopic dermatitis in two Phase 3 trials. August 16, 2021.
Accessed September 14, 2021.
https://www.prnewswire.com/news-releases/lillys-lebrikizumab-significantly-improved-skin-clearance-and-itch-in-people-with-moderate-to-severe-atopic-dermatitis
-in-two-phase-3-trials-301355459.html
.
IL-31 Antagonists: Mechanism of Action in
AD
• AD lesions have overexpression
of Th2 cytokines, including IL-
311
• IL-31 triggers several
pathophysiologic mechanisms
of AD:1,2
• Inflammatory itch
• Disruption of skin barrier function
• Proinflammatory signaling
Image courtesy of Howell MD et al. Front Immunol. 2019;10:2342. CC BY 4.0.

1. Howell MD et al. Front Immunol. 2019;10:2342.

2. Gibbs BF et al. Front Immunol. 2019;10:1383.
 Phase 3 Trial: Nemolizumab vs Placebo in
Adolescents and Adults With AD and Moderate-to-
Severe Pruritus
Nemolizumab Placebo Treatment
(n = 143) (n = 72) difference (95% CI) Enrolled 215
Primary endpoint
Japanese
patients with
-21.5 (-30.2 to -
Change in pruritus VAS at week 16, % -42.8 -21.4 AD aged ≥14
12.7); P <.001
Secondary endpoints years who had
Change in pruritus VAS at day 29, % -34.4 -15.3 -19.3 (-26.6 to -11.9) AD with
Change in EASI at week 16, % -45.9 -33.2 -12.6 (-24.0 to -1.3)
moderate-to-
severe pruritus
Proportion with DLQI score ≤4 at week 16, % 40 22 17 (2-31)
Proportion with decrease of ≥4 points in DLQI at week
67 50 17 (3-31) Common AEs
16, % included
Proportion with ISI ≤7 at week 16, % 55 21 33 (17-48) injection-site
reactions and
worsening of AD
DLQI, Dermatology Life Quality Index; ISI, Insomnia Severity Index; VAS, visual analog scale.

Kabashima K et al. N Engl J Med. 2020;383(2):141-150.

Key Takeaways
• Moderate-to-severe AD is a debilitating disease, with itch as the most
commonly reported bothersome symptom
• There is an unmet need for novel emerging therapies for AD to
improve rates of symptom control
• Oral and topical JAK inhibitors have been shown to improve
outcomes for patients with moderate-to-severe AD
• Novel injectable antagonists of IL-13 or IL-31 have been shown to
improve outcomes in patients with moderate-to-severe AD