New Developments in the Treatment of Atopic …c.peerviewpress.com/inSession/programs/150204065/...Atopic dermatitis is a chronic disease that significantly affects the Updates in

Emma Guttman-Yassky, MD, PhDIcahn School of Medicine at Mount Sinai New York, New York

Course Director

Participate in interactive questions, download activity slides, and obtain your instant CME/MOC credit online.

This CME activity is jointly provided by Medical Learning Institute, Inc. and PVI, PeerView Institute for Medical Education.

CME/MOC New Developments in the Treatment of Atopic Dermatitis: Clinical Highlights From Vienna

What’s Inside

3

6

Updates in Current Treatment Options for Atopic Dermatitis

Emerging Treatments for Atopic Dermatitis: Phase 3 Data Presented at EADV

9 Emerging Treatments for Atopic Dermatitis: Phase 2 Data Presented at EADV

www.peerviewpress.com/RAV900

2 Go online to complete the post-test and evaluation for CME/MOC credit

Activity Information

Expert commentary is based on data presented at the 25th European Academy of Dermatology and Venereology Congress*

Activity Description and Educational ObjectivesIn this activity, a renowned dermatologist discusses new data for current and emerging atopic dermatitis treatments recently presented at the 25th European Academy of Dermatology and Venereology (EADV) Congress in Vienna, Austria.

Upon completion of this activity, participants will be able to:• Discuss emerging data for the efficacy and safety of approved and investigational

atopic dermatitis treatments, as well as the potential clinical impact of these findings

• Apply approaches to treat patients with atopic dermatitis in the context of late-breaking data and patient-, disease-, and therapy-related factors

Target Audience This activity has been designed to meet the educational needs of dermatologists, allergist/immunologists, and other clinicians involved in the management of patients with atopic dermatitis.

Requirements for Successful Completion In order to receive credit, participants must view the activity and complete the post-test and evaluation form. A score of 70% or higher is needed to obtain CME credit. There are no pre-requisites and there is no fee to participate in this activity or to receive CME credit. Statements of Credit are awarded upon successful completion of the post-test and evaluation form.

Media: Enduring MaterialRelease and Expiration Dates: October 28, 2016- October 27, 2017Time to Complete: 30 minutes

Faculty & Disclosure / Conflict of Interest Policy Before the activity, all faculty and anyone who is in a position to have control over the content of this activity and their spouse/life partner will disclose the existence of any financial interest and/or relationship(s) they might have with any commercial interest producing healthcare goods/services to be discussed during their presentation(s): honoraria, expenses, grants, consulting roles, speakers bureau membership, stock ownership, or other special relationships. Presenters will inform participants of any off-label discussions. All identified conflicts of interest are thoroughly vetted by Medical Learning Institute, Inc. for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations.

The associates of Medical Learning Institute, Inc., the accredited provider for this activity, and PVI, PeerView Institute for Medical Education do not have any financial relationships or relationships to products or devices with any commercial interest related to the content of this CME activity for any amount during the past 12 months.

Course DirectorEmma Guttman-Yassky, MD, PhDProfessor and Vice Chair, Department of DermatologyProfessor of Medicine, Clinical ImmunologyDirector of the Center for Excellence in EczemaDirector of the Laboratory of Inflammatory Skin DiseasesIcahn School of Medicine at Mount SinaiNew York, New York

Emma Guttman-Yassky, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant for AbbVie; Almirall; Anacor Pharmaceuticals Inc.; Asana BioSciences, LLC.; Celgene Corporation; Dermiria, Inc.; Galderma; Glenmark Pharmaceuticals Ltd.; Kyowa Hakko Kirin Co., Ltd.; LEO Pharma Inc.; Lilly; MedImmune; Mitsubishi Tanabe Pharma Corporation; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals, Inc.; Sanofi-Aventis; Stiefel Laboratories, Inc./GlaxoSmithKline; and Vitae Pharmaceuticals, Inc. Grant/Research Support from Celgene Corporation; Glenmark Pharmaceuticals Ltd.; Janssen Biotech, Inc.; Lilly; LEO Pharma Inc.; MedImmune; and Regeneron Pharmaceuticals, Inc. Emma Guttman-Yassky, MD, PhD, does intend to discuss either non−FDA-approved or investigational use for the following products/devices: investigational agents and off-label therapies for the treatment of atopic dermatitis.

CME ReviewerMatthew A. Goodman, MDAttending Physician Internal MedicineAbington Jefferson HealthMaple Glen, Pennsylvania

Matthew A. Goodman, MD, has no financial interests/relationships or affiliations in relation to this activity.

CE ReviewerTracy L. Greene, MSN, RN, NP-CConsultantTampa, Florida

Tracy L. Greene, MSN, RN, NP-C, has no financial interests/relationships or affiliations in relation to this activity.

Medical DirectorKate Nelson, PhDPVI, PeerView Institute for Medical Education

Kate Nelson, PhD, has no financial interests/relationships or affiliations in relation to this activity.

DisclaimerThe information provided at this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient's medical condition. Recommendations for the use of particular therapeutic agents are based on the best available scientific evidence and current clinical guidelines. No bias towards or promotion for any agent discussed in this program should be inferred.

Providership, Credit & SupportThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Medical Learning Institute, Inc. and PVI, PeerView Institute for Medical Education. The Medical Learning Institute, Inc. is accredited by the ACCME to provide continuing medical education for physicians.

The Medical Learning Institute, Inc. designates this enduring material for a maximum of 0.5 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the

participant to earn up to 0.5 MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

ProvidershipThis CME activity is jointly provided by Medical Learning Institute, Inc. and PVI, PeerView Institute for Medical Education.

SupportThis educational activity is supported by an educational grant from Sanofi Genzyme and Regeneron Pharmaceuticals.

Disclosure of Unlabeled UseThe faculty of this educational activity may include discussions of products or devices that are not currently labeled for use by the FDA. Faculty members have been advised to disclose to the audience any reference to an unlabeled or investigational use.

No endorsement of unapproved products or uses is made or implied by coverage of these products or uses in our reports. No responsibility is taken for errors or omissions in reports.

Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings.

*PeerView Press is an independent publisher of conference news and medical education programs.

The materials presented here are used with the permission of the authors and/or other sources. These materials do not necessarily reflect the views of PeerView Press or any of its partners, providers, and/or supporters.


3

New Developments in the Treatment of Atopic Dermatitis: Clinical Highlights From Vienna

Dr. Guttman-Yassky: Hello, this is Dr. Emma Guttman. I'm Professor and Vice Chair of the Department of Dermatology at the Icahn School of Medicine at Mount Sinai Medical Center in New York. I would like to welcome you to this educational activity that is focused on updates in atopic dermatitis treatments that were presented at the 25th European Academy of Dermatology and Venereology Congress in Vienna, Austria.

After completing the activity, please access the post-test and evaluation forms by clicking the red "Get Certificate" button. I would like to encourage you to download the slides, Practice Aids, and any other activity features that may interest you.

Atopic dermatitis (AD) has a significant impact on patients

In particular, patients with moderate to severe AD report a significant burden of itch, pain, sleep disturbances, anxiety, depression, and impact on health-related quality of life1

AD can be associated with systemic disease2

Many developments in AD were presented at the 25th EADV Congress

Introduction

1. Guttman-Yassky E. 25th European Academy of Dermatology and Venereology Congress (EADV 2016). P0303.2. Darlenski R et al. Clin Dermatol. 2014;32:409-413.

Atopic dermatitis is a chronic disease that significantly affects the

Updates in Current Treatment Options for Atopic Dermatitis

quality of life of our patients. In particular, patients with moderate to severe disease report a significant burden of itch, pain, sleep disturbances, anxiety, depression, and impact on health-related quality of life.

Additionally, data are emerging that atopic dermatitis has systemic abnormalities—perhaps even more so than psoriasis, another inflammatory skin disease associated with systemic abnormalities. Therefore, we must be able to effectively treat this disease.

Developments in the treatment of atopic dermatitis are continuously being made and many of these advances were recently presented at the 25th European Academy of Dermatology and Venereology, or EADV, Congress in Vienna. Let us begin with a discussion of updates on the current treatments that were presented at EADV.

• Significant improvements in social anxiety observed• Improvements in QOL observed

-20-18-16-14-12-10

-8-6-4-20

n Training groupn Waiting control group

SCO

RA

D In

dex

-20-18-16-14-12-10

-8-6-4-20

Obj

ectiv

e SC

OR

AD

Patient Education in Atopic Dermatitis1

1. Heratizadeh A. EADV 2016.

Patient education is an important component of atopic dermatitis management. A randomized, multicenter study in Germany on the effects of structured patient education on adults with atopic dermatitis was presented. The education was a comprehensive 12-hour training session with a multiprofessional team consisting of a dermatologist, a psychologist, and a dietitian. Significant improvements in the signs of atopic dermatitis were observed with the training group compared with the control group. Therefore, a multidisciplinary approach could be an effective tool to improve outcomes of adult patients with atopic dermatitis.




TCSs

Topical herbal medications

• After TCS administration ± bleach baths, bacterial compositions on lesional skin normalized, resembling that of nonlesional skin• Adding TCSs to presoaked skin was not more effective compared with application to dry skin

• Insufficient evidence for efficacy determined through a systematic review

Topical Treatments at EADV1-4

1. Ibler K. EADV 2016. D2T03.2D.2. Gonzales ME et al. J Am Acad Dermatol. 2016;75:481-493.3. Kohn LL et al. Am Acad Dermatol. 2016;75:306-311.4. Thandar Y et al. EADV 2016. P0299.

A presentation of difficult-to-treat atopic dermatitis included a few recently published studies on the use of topical corticosteroids. For example, one study showed that after topical corticosteroid administration with or without bleach baths, bacterial compositions on lesional skin normalized, resembling that of nonlesional skin. Another study demonstrated that adding topical steroids to presoaked skin was not more effective compared with application to dry skin alone.

Patients frequently seek complementary and alternative medicines for atopic dermatitis. To gain insight on their efficacy and safety, a systematic review of use of topical herbal medicines in atopic dermatitis was conducted and presented at this EADV. Many of the studies included in the analysis had methodological flaws and those showing evidence of efficacy were single trials with only a few patients.

A meta-analysis was not conducted due to heterogeneity seen in the studies. The authors concluded that there was insufficient evidence of efficacy for the use of herbal extracts in atopic dermatitis and more studies are needed to clarify the role of these therapies.

a Azathioprine is not FDA approved for the treatment of AD.

6-TGN

0

100

200

300

400

0

5,000

10,000

15,000

1 2 3 4

0

20

40

60

80

1 2 3 4

400

600

800

1,000

Responders Nonresponders

200

0

AZA 150AZA 50 +

allopurinol100

AZA 50 +allopurinol 100

n 6-MMP

n 6-TGN

AZA Metabolite Monitoring in Patients With AD1,a

1. Garritsen FM. EADV 2016.

Although not approved in the United States for atopic dermatitis, azathioprine is one of the treatment options in the management of severe atopic dermatitis that is not well controlled with topical therapies. However, metabolites of azathioprine may lead to toxicity if a certain level is reached.

A prospective study investigating the relationship between azathioprine dose and the metabolite levels and their correlation with therapeutic response was presented. The findings of the study implied that measurement of azathioprine metabolites in patients with atopic dermatitis is feasible and safe.

Moreover, the addition of allopurinol 100 mg per day to a reduced dose of azathioprine can be useful in patients with metabolite imbalance. However, I must remind you azathioprine is not approved for use in the United States for atopic dermatitis, although we use it off label.

Combined FLG null phenotype was associated with early-onset AD, palmar hyperlinearity, and asthma in the context of AD1

There was no correlation between FLG status and disease severity or treatment response1

Filaggrin expression was similar in children with AD and healthy children2

Role of Filaggrin in AD

1. Kiiski V. EADV 2016. P0305.2. Esaki H et al. J Allergy Clin Immunol. 2016 September 15 [Epub ahead of print].


5


There were also a few studies which explored factors that may predict response to treatment. For example, one study examined associations between filaggrin, or filaggrin null mutations, and atopic dermatitis in a Finnish population. The combined filaggrin null phenotype was associated with early-onset atopic dermatitis, palmar hyperlinearity, and asthma in the context of atopic dermatitis.

However, the filaggrin status did not have an effect on disease severity or on treatment responses. Furthermore, a recently published study that I was involved in found that filaggrin expression was not downregulated in early-onset atopic dermatitis in early childhood, challenging the notion of filaggrin as central for disease elicitation and as an instigator of the entire atopic march.

a Off label.

Total (N = 65)

Responders (n = 33)

Nonresponders (n = 32) P

Male, n (%) 40 (62.5) 23 (69.7) 17 (53.3) .226

Age, y (mean ±) 42.5 (14) 39.9 (14.4) 45.2 (13.1) .132

Duration of MPA tx, d (mean ±) 535 (616.7) 763.1 (753.6) 292 (277.5) .063

UGT1A9-275T>A and -2152C>T heterozygote pts, n (%)

7 (10.7) 1 (3) 6 (18.8) .033

Predicting Response to Mycophenolic Acid in Patients With AD1,a

1. Thijs JL. EADV 2016.

Another study presented examined the prediction of response to mycophenolic acid. At least half of the patients do not respond to this treatment, and nonresponders end up taking the drug for more than 3 months with no benefit, and of course a risk for adverse events.

This retrospective study assessed whether UGT1A9 polymorphisms correlated with nonresponse to treatment with mycophenolic acid in patients with atopic dermatitis. Significantly, more polymorphisms were observed in the nonresponder group. The study found that 18.8% of the nonresponse to mycophenolic acid was explained by the presence of these polymorphisms. A larger prospective study is planned.

These findings highlight the potential for personalized medicine in atopic dermatitis where treatments are prescribed based on patient-specific factors and ineffective treatments for individual patients may be avoided.

a Linear trend.

Factor aOR 95% CI P

Non-flexural location of AD 2.50 1.30-4.79 .006

More severe ADa 0.62 0.49-0.79 .000

AD of the father 0.55 0.35-0.88 .012

Rural living 1.52 1.05-2.20 .026 Condensation in the child’s room 0.60 0.43-0.85 .004

Parental smoking 0.65 0.42-0.99 .044

Breastfeeding <6 mo 1.45 0.99-2.10 .055

Paternal education higher than elementary school 0.64 0.38-1.07 .089

Older agea 1.12 0.99-1.26 .064

Factors Predicting Remission1

1. von Kobyletzki LB. EADV 2016.

An additional study presented at EADV explored factors that predict remission of infant atopic dermatitis until adolescence. The analysis included more than 1,000 patients. The most important predictors were eczema location, the severity of eczema, paternal atopic dermatitis, and a few other parental factors.

So far, we have reviewed updates in currently available atopic dermatitis treatments that were presented at EADV. Stay tuned now for the next segment, where I will discuss new data on emerging therapeutics for atopic dermatitis.



Many patients with moderate to severe AD are not adequately controlled with currently available treatments1

A variety of novel therapies are being investigated for use in AD and studies were presented at the 25th EADV Congress

Emerging Treatment at EADV: Introduction

1. Guttman-Yassky E. 25th European Academy of Dermatology and Venereology Congress (EADV 2016). P0303.

Dr. Guttman-Yassky: Many patients with atopic dermatitis are not adequately controlled with the currently available treatments. Of note—whereas in Europe, oral cyclosporin A is approved for patients with moderate to severe atopic dermatitis—in the United States, only oral prednisone is approved for their treatment. And most dermatologists, including me, would prefer not to use it due to multiple side effects and rebound. And in fact, I [do] not prescribe it.

In a study for which a poster was presented in Vienna, 42% of the patients with moderate to severe atopic dermatitis reported that their current treatments were ineffective. There have not been new therapies developed for the treatment of atopic dermatitis in more than 15 years. However, there are many agents now in development, as presented at this meeting. Let's now examine new treatments presented at EADV.


a P < .0001 for both dupilumab groups vs PBO. b Co-primary endpoint in EU and Japan; key secondary endpoint in other regions.

• Significant improvement in EASI score from baseline in both dupilumab arms versus placebo observed in both studies

• Significant improvements in itch, DLQI, and POEM scores—as well as anxiety and depression—also observed

05

10152025303540

n Dupilumab 300 mg qwn Dupilumab 300 mg q2wn Placebo

SOLO 2 SOLO 1 0

10

20

30

40

50

60

SOLO 2SOLO 1

Patie

nts,

%

Patie

nts,

%

EASI-75 at Week 16a,bIGA = 0 or 1 and ≥2-PointReduction From BL at Week 16a

Emerging Therapies at EADV: Dupilumab1,2

1. Simpson EL. 25th EADV 2016. D3T01.1C.2. Simpson EL et al. N Engl J Med. 2016 Sept 30 [Epub ahead of print].

Dupilumab is a human monoclonal antibody that targets the alpha subunit of the IL-4 receptor, thereby inhibiting the actions of the Th2 cytokines, IL-4 and IL-13. This agent is currently under FDA review for the treatment of adult patients with inadequately controlled moderate to severe atopic dermatitis.

Late-breaking data from the phase 3 SOLO 1 and SOLO 2 trials were presented at this EADV. These were two identical studies in which moderate to severe patients inadequately controlled with topical corticosteroids were randomized to receive placebo, 300 mg dupilumab every 2 weeks, or 300 mg dupilumab weekly for 16 weeks. Both dupilumab doses resulted in a significantly greater proportion of patients achieving an IGA of 0 or 1—that means clear or almost clear—and at least a two-point reduction from baseline compared with placebo. More patients in both dupilumab arms also achieved at least 75% reduction in their Eczema Area and Severity Index, or the EASI score, as compared with placebo. The improvement in EASI score from baseline in both dupilumab arms was significantly greater than that of placebo in both studies. Significant improvements in pruritus or itch were also observed as early as week 2, which is important as itch is a hallmark of atopic dermatitis and a very significant symptom for these patients.

In both studies, both doses of dupilumab were also associated with significant improvement in the Dermatology Life Quality Index and Patient-Oriented Eczema Measures, or POEM, as well as significant improvements in anxiety and depression. So not only does dupilumab improve symptoms, but it also restores the quality of life for patients with atopic dermatitis. Notably, patients in the study had a median affected body surface area of 50%, representing a population with severe atopic dermatitis or severe eczema for which there is a significant unmet need for novel treatments.



7


Duration of AD: 48 years

16 weeks• IGA: 4• BSA: 86.5%• EASI: 51.5• Pruritus NRS: 7

• IGA: 1• BSA: 2.5%• EASI: 3.1• Pruritus NRS: 1.6

Example of Patient Who Achieved Primary Endpoint With Weekly Dupilumab Treatment1

1. Simpson E. EADV 2016. D3T01.1C.

An example of a patient who achieved the primary endpoint with dupilumab weekly was presented. This was a patient with a duration of atopic dermatitis of 48 years. At week 16, the patient's IGA score decreased from 4 to 1, the affected body surface area went from about 86.5% to 2.5%, and the EASI score went from 51.5 to only 3.1. And the pruritus NRS decreased from 7 to 1.6.

In general, dupilumab was well tolerated. Most adverse events were mild or moderate. Injection site reactions and conjunctivitis were more frequent with dupilumab. There were no observed increases in infection with dupilumab. Therefore, dupilumab represents a promising option for adult patients with moderate to severe atopic dermatitis.

We are very excited that there is a new treatment that provides better safety and efficacy than the existing treatment options, and can be used long term as we currently do not have effective treatments that can also be used long term for our patients with severe atopic dermatitis.

a MCID: ≥2.5-point reduction from BL.2 b MCID: ≥3.3-point reduction from BL.3

Crisaborole also significantly improved the QOL of the families, parents,or caregivers of patients aged 2-17 years, assessed via DFI Questionnaire

-5

-4

-3

-2

-1

0

n Vehicle (n = 355)

n Crisaborole (n = 750)

Baseline Overall Score

-6

-5

-4

-3

-2

-1

0

Baseline Overall ScorePatients Aged 2-15 ya Patients Aged ≥16 yb

P < .001CD

LQI O

vera

ll Sc

ore,

Mea

n C

hang

e Fr

om B

L

DLQ

I Ove

rall

Scor

e,M

ean

Cha

nge

From

BL

P = .016

n Vehicle (n = 82)

n Crisaborole (n =180)

9.3 9.0 9.7 9.3

Emerging Therapies at EADV: Crisaborole1

1. Paller AS. EADV 2016. FC02.08.2. Langley RG et al. J Am Acad Dermatol. 2011;64:64-70.3. Basra MK et al. Dermatology. 2015;230:27-33.

Another atopic dermatitis treatment that is under FDA review is crisaborole, a topical phosphodiesterase inhibitor. This agent is being investigated for the treatment of mild to moderate atopic dermatitis in both children and adults. Recently published phase 3 studies showed improvement with crisaborole versus placebo in all measures of efficacy, including overall disease severity, pruritus, and other signs of atopic dermatitis. Results from these studies, demonstrating the effects of crisaborole on quality of life, were presented in Vienna. Crisaborole was associated with significant improvements in quality of life in both age groups—2-15 years old and also 16 and above—for patients as well as their families.

Safety data pooled from two phase 3 studies and OLE study

• Pooled TEAEs occurred at a low frequency across all age groups and over time

• Majority of TEAEs were considered mild or moderate and not related to treatment

• Most common TEAEs: – Atopic dermatitis (3.1%) – Application site pain (2.3%) – Application site infection (1.2%)

Long-Term Safety of Crisaborole1

1. Eichenfield L. EADV 2016. FC01.02.



The long-term safety of crisaborole was investigated in patients 2 years of age and older with mild to moderate atopic dermatitis who were included in an open-label extension of the phase 3 studies.

Safety data were pooled from the two 28-day phase 3 studies, as well as the open-label, 48-week safety study. Pooled treatment-emergent adverse events occurred at a low frequency across all age groups and over time. The most frequently reported treatment-emergent adverse events were atopic dermatitis (3.1%), application site pain (2.3%), and application site infection (1.2%). The majority of treatment-emergent adverse events were considered mild or moderate and not related to treatment. There were no reports of long-term cutaneous adverse reactions.

In the extension study, none of the reported serious adverse events were considered treatment related. Less than 2% of patients discontinued the extension study due to treatment-emergent adverse events. Therefore, the safety profile of crisaborole topical ointment 2% was favorable for long-term treatment of patients age 2 years and older with mild to moderate atopic dermatitis.

We are excited to have new and safe topical treatments for our patients with atopic dermatitis.


9



a P < .05 vs PBO.

EASI-50 at Week 12

Lebrikizumab 125 mg q4w resulted in:

• Significantly higher proportions of patients achieving EASI-50, EASI-75, and SCORAD-50

• Trends for improvement in IGA 0/1 and pruritus VAS

SCORAD-50 at Week 12

Prop

ortio

n of

Pat

ient

s, %

Prop

ortio

n of

Pat

ient

s, %

0

20

40

60

80

100

125 mgq4w

250 mgSD

125 mgSD

Placebo0

10

20

30

40

50

60

125 mgq4w

250 mgSD

125 mgSD

Placebo

a aa

Emerging Therapies at EADV: Lebrikizumab1

1. Simpson E. 25th European Academy of Dermatology and Venereology Congress (EADV 2016). D3T01.1F.

[A] late-breaking presentation of phase 2 data was for treatment of moderate to severe atopic dermatitis patients with lebrikizumab. Lebrikizumab is a humanized monoclonal antibody that binds IL-13, a key Th2 cytokine, with an important role in the pathogenesis of atopic dermatitis.

The patients included in the study were 18-75 years old with moderate to severe atopic dermatitis for at least a year with an inadequate response to topical corticosteroids. The patients were randomized to receive either placebo or lebrikizumab 125 mg single dose, 250 mg single dose, or 125 mg every 4 weeks. All patients also received topical corticosteroids twice daily.

Dosing every 4 weeks resulted in significantly higher proportions of patients achieving 50% and 75% improvements in the EASI scores, as well as 50% improvement in the SCORAD scores, another scoring index for atopic dermatitis, with trends for improvement in pruritus and the proportions of patients achieving clear or almost clear skin.

Significant improvements were also seen in the placebo group, and it would be good to have a monotherapy study in the future to really evaluate for drug effect without the effect of topical steroids. Adverse events were similar between treatment groups, and most were mild or moderate in severity.

Perc

enta

ge o

f Res

pond

ers

0

5

10

15

20

25

30

≥2-point drop andscore of 0 or 1

≥2-point drop

P = .005

P = .057

n PBO n 2 g DS107

-60-50-40-30-20-10

0 2 4 6 8Time, wk

VAS for Pruritus

Cha

nge

From

Bas

elin

e, %

P = .154

P = .015 P = .450

-9-7-5-3-10 2 4 6 8

Time, wkPOEM

Cha

nge

From

Bas

elin

e

P = .064

P = .013P = .380

IGA

Emerging Therapies at EADV: DS1071

1. Thaci D. EADV 2016. FC03.01.

DS107 is another emerging treatment being studied in atopic dermatitis. This drug contains the active pharmaceutical ingredient DGLA, a 20-carbon polyunsaturated bioactive lipid. A phase 2a proof-of-concept study was presented in patients with moderate to severe atopic dermatitis.

Analysis of the primary endpoint, which was at least a two-point decrease in the IGA and a score of 0 to 1 showed a trend in favor of DS107 over placebo at 8 weeks. There was an increase in the number of responders when only patients who completed 8 weeks of treatment, the observed population, were included in the analysis.

A post hoc analysis showed statistically significant decreases in IGA score with DS107 compared with placebo when patients were stratified by site and severity of the atopic dermatitis at baseline. Statistically significant improvements in pruritus and POEM scores were also observed after 4 weeks.

DS107 capsules were well tolerated up to 2,000 mg on single dose. The majority of adverse events were GI-related, transient, and resolved without any intervention.




% Change in PruritisVAS at Week 12

Nemolizumab improved:• Pruritis• Dermatitis• Sleep • Quality of life

-70

-60

-50

-40

-30

-20

-10

0

n Placebo (n = 43)

n 0.1 mg/kg (n = 44)

n 0.5 mg/kg (n = 43)

n 2 mg/kg (n = 46) -80

-70-60-50-40-30-20-10

0

0 1 2 3 4 5 6 7 8 9 10 11 12

Time Course of % Change of Pruritus VAS

n Placebon 0.5 mg/kg q4w

n 0.1 mg/kg q4wn 2.0 mg/kg q4w

(n = 25-46)

(n = 32-46)(n = 32-47)(n = 34-45)

Emerging Therapies at EADV: Nemolizumab1

1. Ruzicka T. EADV 2016. FC04.02.

Nemolizumab is a monoclonal antibody that targets IL-31—the itch cytokine—for which phase 2 data were presented at EADV. There was a rapid dose response reduction of the pruritus. Sleep and quality of life were also improved. Improvements in dermatitis, as determined by EASI, and achievement of an sIgA [secretory Immunoglobulin A] of 0 to 1 were also observed. Frequent adverse events occurring in at least 5% of patients included worsening of atopic dermatitis, nasopharyngitis, upper respiratory tract infections, and peripheral edema. No increases in infection or death were observed with nemolizumab.

A phase 2 study of adults with moderate to severe AD demonstrated that ustekinumab resulted in higher SCORAD-50 responses at week 12, 16 (primary endpoint), and 20 compared with placebo, but the difference between groups was not significant

Lack of effect could be due to small sample size, background TCS use, and/or insufficient dosing for AD

Emerging Therapies at EADV: Ustekinumab1

1. Khattri S et al. Exp Dermatol. 2016 June 15 [Epub ahead of print].

A recently published phase 2 study investigating a treatment used for psoriasis targeting the P40 subunit of both IL-12 and [IL]-23 cytokines—namely ustekinumab—in adult patients with atopic dermatitis was also presented. The ustekinumab group achieved higher SCORAD-50 responses at week 12, 16 weeks (which was the primary endpoint), and 20 weeks compared to placebo. But due to the small sample size, the difference between groups was not significant. This can also be due to the use of topical steroids and the use of the psoriasis dosing regimen, which may not be sufficient for patients with atopic dermatitis that may have higher systemic immune activation.

• At week 4, 73% of patients receiving tofacitinib achieved PGA ≤1 vs 22% of those receiving the control vehicle

• A significant reduction in itch was also observed with tofacitinib

• The most frequent treatment- emergent adverse event was respiratory tract infection, but in general adverse events with tofacitinib were similar to vehicle

-100

-80

-60

-40

-20

0

0

20

40

60

80

100

Baseline Week 1 Week 2 Week 4

Time point

Baseline Week 1 Week 2 Week 4

Time point

LS M

ean

(SE)

Per

cent

age

Cha

nge

From

BL

inEA

SI T

otal

Sco

re

Prop

ortio

n (S

E) o

f Pts

Ach

ievi

ng P

GA

Res

pons

eof

Cle

ar o

r Alm

ost C

lear

+≥2

-Poi

nt Im

prov

emen

t Fro

m B

L

n 2% tofacitinib twice dailyn Vehicle twice daily

Emerging Therapies at EADV: Tofacitinib1,2

1. Bachelez H. EADV 2016. DT210.2D. 2. Bissonnette R et al. Br J Dermatol. 2016 Jul 16 [Epub ahead of print].

The next study I would like to talk about is a phase 2a trial investigating the use of topical JAK inhibitor tofacitinib in atopic dermatitis. At week 4, 73% of patients receiving tofacitinib achieved a Physician Global Assessment, or PGA, score of 0 to 1, compared with only 22% of those receiving the control vehicle. A significant reduction in itch was also observed with tofacitinib. The most frequent treatment-emergent adverse event was respiratory tract infections, but in general adverse events with tofacitinib were similar to the vehicle.


11


Overall EASI Score Over Time

Treatment: n QGE031 n Placebo n Cyclosporine

Treatment Period Follow-Up Period

Clin

ical

Impr

ovem

ent

Dosing

Week

0

10

20

30

Week 0 Week 2 Week 4 Week 6 Week 8 Week 10 Week 12 Week 14 Week 16 Week 18 Week 20 Week 22 EOSSCR

High-Affinity IgE Antibody: Clinical Efficacy1

1. Bangert C. EADV 2016. FC03.03.

In this meeting, we obtained this time the final proof we needed for the lack of a pathogenic role of IgE in atopic dermatitis since a high-affinity anti-IgE molecule achieved no clinical benefit in patients with moderate to severe atopic dermatitis.

• Atopic dermatitis has a significant effect on the lives of patients

• New insights are emerging for current treatments, including factors that predict response to therapy

• With a variety of therapies under development, the treatment paradigm for AD is likely to evolve in the near future

Conclusions

So to conclude, atopic dermatitis has a significant impact on patients and their lives. New insights are emerging on current treatments, including factors that can predict response to treatment. Studies have challenged the previously conceived notions of filaggrin and IgE playing important roles in the development of atopic dermatitis. Two new treatments, dupilumab and crisaborole, are under FDA review and may be available soon, and a variety of other treatments are in phase 2 of development. Therefore, the treatment of atopic dermatitis is likely to evolve in the near future and it is a very exciting time in this field for patients and their physicians. It will be important to have monotherapy studies conducted, as the background use of topical corticosteroids may affect and interfere with the interpretation of the clinical effects of these agents, as we [saw] in this meeting.

Well, that ends our discussion for today. I hope you found it informative and useful. Once again, I encourage you to download the slides and Practice Aids for this activity. Don't forget to access the post-test and evaluation form by clicking the red "Get Certificate" button. Thank you very much for participating in this educational activity focused on updates in atopic dermatitis presented at the 25th EADV Congress.

CME/MOC New Developments in the Treatment of Atopic Dermatitis: Clinical Highlights From Vienna


Sign up for e-mail alerts on new clinical advances and educational activities in your specialty: www.peerviewpress.com/signup

Copyright © 2000-2016, PeerView Press

This CME activity is jointly provided by Medical Learning Institute, Inc. and PVI, PeerView Institute for Medical Education.

This educational activity is supported by an educational grant from Sanofi Genzyme and Regeneron Pharmaceuticals.

PVI, PeerView Institute for Medical Education, and Medical Learning Institute, Inc. are responsible for the selection of this activity's topics, the preparation of editorial content, and the distribution of this activity. The preparation of PeerView activities is supported by educational grants subject to written agreements that clearly stipulate and enforce the editorial independence of PVI and Medical Learning Institute, Inc. Our activities may contain references to unapproved products or uses of these products in certain jurisdictions. For approved prescribing information, please consult the manufacturer's product labeling. No endorsement of unapproved products or uses is made or implied by coverage of these products or uses in our activities. No responsibility is taken for errors or omissions in activities.

New and improved source for free CME/CE

Expert commentary is based on data presented at the 25th European Academy of Dermatology and Venereology Congress**PeerView Press is an independent publisher of conference news and medical education programs.

Documents

New Developments in the Treatment of Atopic …c.peerviewpress.com/inSession/programs/150204065/...Atopic dermatitis is a chronic disease that significantly affects the Updates in