● Atopic dermatitis (AD) is a chronic inflammatory skin disease,1 characterized by eczematous lesions and multiple 
 symptoms including pruritus, sleep disturbance, and depression2,3

● Tralokinumab is a first-in-class, fully human monoclonal antibody, designed to neutralize interleukin-13, a key 
 driver of the underlying inflammation of AD which is overexpressed in lesional and non-lesional AD skin4,5

● The ECZTRA 3 study reflected clinical practice by evaluating the use of tralokinumab 300 mg every 2 weeks in 
 combination with a topical corticosteroid (TCS) used as needed on active lesions compared with placebo plus 
 TCS as needed6

● Tralokinumab plus TCS demonstrated superiority versus placebo plus TCS in achieving the primary endpoints of 
 an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) [IGA-0/1] and a 75% improvement 
 in Eczema Area and Severity Index (EASI-75) at week 166

● Use of IGA and EASI as primary outcomes in clinical studies is driven in part by guidance from regulatory 
 authorities such as the U.S. Food and Drug Administration and the European Medicines Agency
● Patient−clinician discussions around the decision to continue, switch, combine, increase dose, or stop therapy 
 should be based on a more comprehensive assessment of treatment and response7

● The Harmonising Outcome Measures for Eczema (HOME) initiative suggested that comprehensive assessment 
 of long-term control of AD should include domains of signs, symptoms, quality of life, and a patient global 
 instrument8

Patients and study design
● ECZTRA 3 enrolled adults with a diagnosis of AD for more than 1 year and a recent history of inadequate 
 response to treatment with topical medications (Figure 1)
● Patients were randomly assigned (2:1) to either subcutaneous tralokinumab 300 mg every other week plus TCS 
 or placebo every other week plus TCS for 16 weeks, after which tralokinumab responders (IGA-0/1 and/or 
 EASI-75) were re-randomized 1:1 to continuation treatment with tralokinumab 300 mg every other week or every 
 4 weeks plus TCS for an additional 16 weeks

Tralokinumab q4w + TCS (n=69)

Tralokinumab q2w + TCS (n=69)

Screening Continuation treatment
Clinical response defined as 

IGA-0/1 or EASI-75 O�-treatment
period

Safety
follow-up

0–6 weeks 32 weeks 46 weeks16 weeks

n=253

n=127

The post-hoc analyses focused on pooled data from all patients who were randomized to 
tralokinumab at the start of the study

2:1 randomization

1:1  re-randomization

Washout of  TCS
and other AD
medication

Initial treatment
300 mg q2w after initial
 loading dose (600 mg)

16-week responders

16-week non-responders

16-week responders

16-week non-responders

Tralokinumab q2w + TCS (n=95)

Placebo q2w + TCS (n=41)

Tralokinumab q2w + TCS (n=79)

Tralokinumab q2w + TCS

Placebo q2w + TCS

Figure 1. ECZTRA 3 trial design (NCT03363854)6

P
a

ti
e

n
ts

 a
ch

ie
vi

n
g

 t
a

rg
e

t,
 %

100

10

20

30

50

40

60

70

80

90

0
All patients

204/252

PGI-B + any other 
target at week 12

175/193

All patients

174/252

PGI-B + any other
target at week 12

148/193

EASI-50 at
week 24

EASI-75 at
week 24

81%

91%

69%

77%

Figure 3. Impact of holistic assessment of response at month 3 on achievement of EASI improvement with 
tralokinumab q2w or q4w plus TCS at month 6

Disease domain and scoring
Initial treatment phase minimal 
target (clinically relevant change 
versus baseline after 3 months)

Maintenance treatment phase ideal target 
(mild disease activity after 6 months)

Table 1. Disease domains and targets assessed

aWeekly average of worst daily score, 11-point scale, 0 = “no itch” to 10 = “worst itch imaginable”; bWorst score recorded during the week, 5-point scale, 0 = “not at all” to 4 = “very 
much”; c10 items addressing impact of skin disease over the last week, 4-point scale, 0 = “not at all, not relevant” to 3 = “very much”; dMeasured at week 20; eTotal frequency of 7 
symptoms over the last week (itching, sleep, bleeding, weeping, cracking, flaking, and dryness), 5-point scale, 0 = “no days” to 4 = “every day”

Week 16, n (%)
Placebo q2w + TCS

(n=126)
Tralokinumab q2w + TCS

(n=252)

Table 3. Adverse events in the initial treatment period up to week 16

AE, adverse event, aPreferred terms according to Medical Dictionary for Regulatory Activities, version 20.0.

Tralokinumab q2w + TCS
(n=253d)

aIncludes USA and Canada; bIncludes Belgium, Germany, Netherlands, Poland, Spain, and UK; cPGI-B: 0: “not at all”, 1: “slightly”, 2: “somewhat”, 3: “a lot”, or 4: “very much”; dOne patient 
was not dosed due to use of prohibited medication and was therefore excluded from the full analysis set.

Tralokinumab improves clinically relevant outcome measures: a post hoc analysis of ECZTRA 3, a randomized clinical trial in patients with moderate-to-severe atopic dermatitis
1Stephan Weidinger,1 Andrew E. Pink,2 Juan Francisco Silvestre,3 Azra Kurbasic,4 Christina Kurre Olsen,4 Andreas Westh Vilsbøll,4 Marjolein de Bruin Weller5

1Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany; 2St. John’s Institute of Dermatology, Guy’s and St. Thomas’ Hospitals, London, UK; 3Dermatology Department, Hospital General Universitario de Alicante, Alicante, Spain; 4LEO Pharma A/S, Ballerup, Denmark; 5Department of Dermatology and Allergology, University Medical Center Utrecht, National Expertise Center for Eczema, Utrecht, The Netherlands 

Patient characteristics
● Patients had a long duration of AD prior to being enrolled into the study; almost half of patients had severe AD 
 (IGA-4) at baseline and mean body surface area (BSA) involvement was close to 50% (Table 2)
● Overall, 60% of patients had a worst PGI-B score of 4 (very much bothered by their AD) at baseline

● ECZTRA 3 included assessment of:
 - IGA and EASI assessed every 2 weeks 
 - Patient Global Impression of Bother (PGI-B) and Numerical Rating Scale (NRS) for worst daily pruritus 
  assessed daily and recorded as the worst weekly and daily score respectively 
 - Dermatology Life Quality Index (DLQI) and Patient-Oriented Eczema Measure (POEM) assessed bi-weekly 
  until week 8, every 4 weeks until week 20, and then at week 28 and 32

Post hoc analysis
● Following HOME recommendations,8 outcomes were selected in the domains o clinician-assessed signs (EASI), 
 patient-reported symptoms (pruritus NRS and POEM) quality of life (DLQI), and a patient global instrument 
 (PGI-B) (Table 1) 
● Outcomes were assessed at time points typically used in clinical practice for patient follow-up, i.e. after 
 3 months in the initiation phase and every 6 months in the maintenance phase
● Clinically relevant targets were selected to reflect the achievement of a clinically meaningful change versus 
 baseline during the initial treatment phase (minimal target) and to reflect achievement of mild disease activity 
 (ideal target) during the maintenance phase

aMeasured at week 20. Pruritus NRS assessed in patients with worst daily pruritus NRS 3 at baseline; DLQI and POEM assessed in patients with DLQI/POEM total score 
4 at baseline; PGI-B assessed in patients with PGI-B 1 at baseline.

Introduction

Results

Methods

Objective
● The objective of this post hoc analysis was to assess response to tralokinumab in combination with TCS 
 as needed, based on outcome domains and time points typically used in clinical practice

2020 Fall Clinical Dermatology Conference, October 29-November 1, 2020, Live Virtual Meeting

● This post hoc analysis included pooled data from all patients who were randomized to tralokinumab plus TCS 
 at the start of ECZTRA 3 to assess: 
 - The proportion of tralokinumab plus TCS-treated patients who achieved the individual disease domain 
   targets at 3 and 6 months
 - The impact of selecting patients by holistic assessment at month 3 on the proportion achieving meaningful 
  improvement in the extent and severity of lesions (EASI-50 or EASI-75) at month 6
  • Subgroup analyses of patients achieving both a perceived improvement in the overall disease burden 
   (PGI-B) AND a meaningful improvement in any one of the other targets at 3 months

Statistical analyses
● Post hoc analysis was based on the full analysis set and included all patients who received tralokinumab plus 
 TCS in the initial treatment period 
● In the assessment of the defined binary targets, subjects who received rescue medication were considered 
 non-responders and subjects with missing data were imputed as non-responders

Table 2. Patient demographics and disease characteristics at baseline

EASI-50
79% (199/252)

Worst PGI-B
�1-point
reduction
79% (199/252)

DLQI �4 point
reduction
77% (191/248)

POEM �4-point
reduction

78% (195/250)

Worst pruritus
NRS �3 point

reduction
59% (148/251)

Patients achieving any of the five defined minimum
initiation phase targets after 3 months = 91% (225/247)

A

B

0%

20%

40%

80%

100%

EASI �7
69% (147/252)

Worst PGI-B
absolute
score �2
43% (108/252)

DLQI absolute
score �5a
59% (146/248)

POEM absolute
score �7a

37% (93/250)

Worst pruritus
NRS absolute

score �4
61% (152/251)

Patients achieving any of the five defined optimal
maintenance phase targets after 6 months = 82% (202/247)

60%

0%

20%

40%

80%

100%

60%

Figure 2. Proportion of patients achieving the individual disease domain targets for (A) clinically relevant change 
at 3 months and (B) mild AD activity at 6 monthsa

Safety
● Tralokinumab in combination with TCS was well tolerated with the overall safety being comparable to that of 
 placebo in the initial treatment period up to 16 weeks (Table 3). Overall, the safety profile at week 32 was 
 comparable with the initial treatment period
● Tralokinumab in combination with TCS was associated with lower rates of severe and serious infections and 
 eczema herpeticum versus placebo plus TCS
● All conjunctivitis cases were mild to moderate and only one led to treatment discontinuation

● Overall, 82% of patients receiving tralokinumab every 2 weeks or every 4 weeks plus TCS achieved at least one 
 of the defined optimal targets (equivalent to mild disease) at month 6 in the maintenance treatment phase 
 (Figure 2B)
 - 59−69% achieved mild AD as judged by EASI, DLQI, and worst daily pruritus NRS
 - 37% and 43% of patients achieved mild AD as judged by POEM or worst weekly PGI-B, 
  respectively
● Overall, 78% (193/247 patients with data at baseline and month 3) achieved both a 1-point reduction in PGI-B 
 and at least one of the other disease domain endpoints at month 3
● Response rates for EASI-50 and EASI-75 at month 6 were higher in the subgroup of patients who achieved both 
 a 1-point reduction in PGI-B and at least one of the other disease domain endpoints at month 3, compared 
 with the whole cohort (Figure 3)

Conclusions
● Tralokinumab 300 mg every other week in combination with TCS as needed was 
 associated with a high proportion of patients (91%) achieving a clinically meaningful 
 improvement (minimal target) in at least one of the pre-defined disease domains 
 (AD signs and symptoms and AD-related quality of life) 3 months after initiating 
 treatment

● A high proportion of patients (82%) achieved an outcome equivalent to mild disease 
 activity (ideal target) in at least one of the pre-defined disease domains (AD signs and 
 symptoms and AD-related quality of life) during the maintenance treatment phase 

● Using a holistic approach combining the achievement of the patients’ impression 
 of burden target (PGI-B) in combination with one other initiation period target 
 increased the proportion of patients who achieved EASI-50 and EASI-75 in the 
 maintenance period

● This post hoc assessment is in line with previous data showing that IGA and EASI 
 scores do not correlate perfectly with symptom outcome measures and suggest that 
 jointly agreed treatment targets between patients and the clinician are important, as 
 are holistic assessments

References
1. Weidinger S, Novak N. Lancet 2016; 387: 1109–1122. 2. Silverberg JI et al. Ann Allergy Asthma Immunol 2018; 121: 340–347. 3. Dalgard FJ et al. J 
Invest Dermatol 2015; 135: 984–991. 4. Bieber T. Allergy 2020; 75: 54–62. 5. Tsoi LC et al. J Invest Dermatol 2019; 139: 1480–1489. 6. Weidinger S et 
al. Oral presentation at the American Academy of Dermatology Virtual Meeting, 2020. 7. Thyssen JP et al. J Eur Acad Dermatol Venereol 2020; 
doi: 10.1111/jdv.16716. 8. Chalmers JR et al. Br J Dermatol 2018; 178: e332–e341.

Disclosures
Stephan Weidinger has acted as an advisory board member/speaker/investigator for, and/or has received grants/research funding from, 
AbbVie, Almirall, Laboratorie Pharmaceutique, La Roche-Posay, LEO Pharma, Lilly, Novartis, Pfizer, Sanofi Genzyme, and Sanofi/Regeneron. 
Andrew E. Pink has acted as an adviser or speaker for AbbVie, Almirall, Janssen, La Roche-Posay, LEO Pharma, Lilly, Novartis, Pfizer, Sanofi, 
and UCB. Juan Francisco Silvestre has acted as a consultant/advisor for AbbVie, Novartis Regeneron, and Sanofi Genzyme. Azra Kurbasic, 
Christina Kurre Olsen, and Andreas Westh Vilsbøll are employees of LEO Pharma. Marjolein de Bruin Weller has acted as a consultant/advisor 
for AbbVie, LEO Pharma, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and UCB, and has received grant/research support from Regeneron and 
Sanofi Genzyme.

The tralokinumab ECZTRA 3 study was sponsored by LEO Pharma

Target achievement at months 3 and 6
● Overall, 91% of patients receiving tralokinumab every 2 weeks plus TCS achieved at least one of the defined 
 minimum targets (clinically relevant change) for EASI, pruritus, POEM, DLQI, and PGI-B at 3 months (Figure 2A)
 - 77-79% achieved a clinically relevant change as judged by EASI, PGI-B DLQI, and POEM, respectively
 - 59% achieved a clinically relevant change as judged by worst daily pruritus NRS