Expert opinion

Podcast 1: JAK inhibitors and the evolving treatment landscape for atopic dermatitis

Listen in on this short and engaging podcast to hear Professor Jacob Thyssen and Professor Jonathan Silverberg discuss recent approval indications of JAK inhibitors in Europe and the US to treat atopic dermatitis. In this session they cover the mode of action, safety and efficacy of JAK inhibitors, including clinical trial evidence, the differences in the adverse events between JAK inhibitor treatment options and a comparison between JAK inhibitors and other commonly prescribed systemic therapies.

Podcast 2: Monoclonal antibody treatment for atopic dermatitis

In this episode Professor Jacob Thyssen is joined by Professor Andreas Wollenberg to discuss new and emerging treatment options for atopic dermatitis including the recent approval of the monoclonal antibody tralokinumab in Europe and the United States. They describe clinical data from Phase 2 clinical trials, discuss safety profiles, and highlight the importance of tailoring treatment for the patient in the face of the evolving treatment landscape. In addition, the professors discuss the pathophysiology of atopic dermatitis including the possible relevance of cytokines in disease management.

Podcast 3: Integration of new atopic dermatitis treatments into clinical practice

In this last episode of the series, Professor Jacob Thyssen discusses with Professor Tiago Torres how new approvals have changed the treatment landscape for atopic dermatitis and how to integrate these new options into clinical practice. Join them to gain insight into how to identify the most suitable treatment for different patients depending on their specific circumstances, including the presence of comorbidities and how to advance towards a more personalised medicine. You’ll learn about the challenges present in the treatment landscape today and some ways to overcome these barriers.

Meet the experts

Dr. Thyssen has been with the University of Copenhagen for more than twenty years, where he currently serves as tenured professor, while also working as chief physician at Bispebjerg Hospital, the largest Dermatology department in Denmark. Dr. Thyssen has a PhD in epidemiology and did his doctorate (DmSci) with focus on eczema. He has been a research fellow at Harvard Medical School, Boston, the University of California, San Francisco and University Spital Zürich, Switzerland, where his research focused on atopic dermatitis and the complexity of the skin barrier. Dr. Thyssen is active in clinical development of new treatments targeting inflammatory skin diseases. He acts as a consultant for pharmaceutical companies, chairman of data safety monitoring boards, and gives testimonies to EMA during assessments of novel drug applications.

Dr Thyssen reported receiving personal fees from AbbVie for speaking and advising during the conduct of the study; and receiving grants from Regeneron, Sanofi Genzyme, and Pfizer and personal fees from Leo Pharma, Lilly, OM-85, Almirall, Asana, and Arena outside the submitted work.

Jonathan Silverberg is a Professor of Dermatology at The George Washington University School of Medicine and Health Sciences in Washington, DC. He is the Director of Clinical Research and Contact Dermatitis. Dr. Silverberg’s area of clinical subspecialty is inflammatory skin disease, particularly atopic and contact dermatitis. He has extensive experience in the advanced management of atopic dermatitis, contact dermatitis, hand eczema, chronic itch, psoriasis, hidradenitis and many other chronic inflammatory skin disorders. He is also a national expert in allergy patch testing, phototesting and photopatch testing. 

Dr Silverberg reports receiving honoraria as a consultant and advisory board member from LEO Pharma A/S and acting as a consultant for and/or receiving grants and honoraria from AbbVie Inc, AnaptysBio, Inc, Asana, Galderma, Glax- oSmithKline, Glenmark, Kiniksa Pharmaceuticals, Ltd, LEO Pharma A/S, Eli Lilly and Company, MedImmune, LLC, Menlo, Pfizer Inc, PuriCore, Inc, Regeneron Pharma-ceuticals Inc, and Sanofi.

Professor Andreas Wollenberg is a dermatologist and allergist and Professor in the Department of Dermatology and Allergy, Ludwig-Maximilian University of Munich, Germany. He is board certified in dermatology and venereology and holds subspecialty certification in allergology, andrology and infectious diseases.

His research interests include immunobiology of dendritic cells in inflammatory skin diseases, infectious complications, topical immunomodulating therapy, and drug-induced skin toxicity. Professor Wollenberg has made a significant contribution in advancing understanding of the central role of epidermal dendritic cells in the pathogenesis of atopic dermatitis. He has performed many clinical trials and translational research projects relating to atopic dermatitis, perioral dermatitis, graft-versus host disease and drug reactions and has coined the term ‘proactive therapy’ of atopic dermatitis. He is secretary of the EADV’s European Task Force on Atopic Dermatitis. He has authored more than 140 papers in peer-reviewed international journals.

Andreas Wollenberg has received personal fees for lectures or advisory boards, grants or non-financial support from Abbvie, Aileens, Almirall, Arena, Beiersdorf, Galderma, Leo Pharma, Eli Lilly, L’Oreal, Maruho, MedImmune, Novartis, Pfizer, Pierre Fabre, Regeneron and Sanofi-Aventis.

Tiago Torres is Professor of Dermatology at the Instituto de Ciências Biomédicas Abel Salazar, University of Porto. Currently, he is the Head of the Immunodermatology Unit (psoriasis, atopic dermatitis and auto-immune diseases) of the Department of Dermatology of CHUP. Through the years has been principal investigator for several psoriasis and atopic dermatitis clinical trials. He has been involved in the development of national guidelines for the treatment of psoriasis and atopic dermatitis, has received the “Juvenal Esteves” Prize from the Portuguese Society of Dermatology and Venerology with research projects in psoriasis and psoriatic arthritis in 2011, 2013, 2017 and 2018. In 2018 received two Sanofi-Genzyme grants for atopic dermatitis projects. He is currently President of the Portuguese Group of Psoriasis, founding member of the Portuguese Group of Atopic Dermatitis and an IPC, GRAPPA, SPIN and IEC member; and has published more than 100 articles on psoriasis and atopic dermatitis.

Tiago Torres has received research grants and/or consulting fees from AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Samsung-Bioepis, Sandoz, Sanofi and Viatris. 

What is the importance of epidermal hyperplasia in atopic dermatitis?

A combination of factors influences the development of epidermal hyperplasia in atopic dermatitis. Hear Professor Desai add insight into what is known of its pathogenesis. Further your understanding of the pathways involved in epidermal hyperplasia, knowledge which is key to providing targeted therapeutics and realising improvements for patients.

Can you describe some of the key hypotheses and research areas for the pathogenesis of atopic dermatitis?

Refresh your knowledge of the complex molecular interactions that influence the development of atopic dermatitis. As we learn more about the inflammatory response involved, Professor Desai focuses attention on key cytokines associated with cellular responses mediated by the JAK-STAT signalling pathway.

How can understanding of the role of Janus kinase (JAK) proteins in atopic dermatitis help target treatment?

For patients with moderate-to-severe atopic dermatitis, where there are limitations to treatment with topical agents or systemic immunosuppressants, finding more targeted therapies is key. Professor Desai is involved in clinical trials and a leader within the FDA – well placed to explain the thinking behind the development and use of therapeutics. Listen to him explore molecules that target the involvement of Janus kinase proteins in membrane binding and signalling.

Which cytokines are key targets in atopic dermatitis?

Are you up to date with the latest research and understanding of cytokines that play a key role in moderate-to-severe atopic dermatitis? Find about more about the central players in this auto-inflammatory skin disease.

Which investigational treatments offer exciting potential for the treatment of atopic dermatitis?

Hear Professor Desai explore the promise of a number of specific JAK inhibitor pipeline molecules, including where they are in clinical trials and if and when we might hope to see them available for use.

What are key topics of discussion with patients for clinicians treating moderate to severe atopic dermatitis?

It is vital for those involved in treating atopic dermatitis to keep patient priorities central to their clinical approach. Ensure you are clear about the interplay between patient and clinician goals in order to effectively manage consultations and remember the key topics to explore with those living with the reality of atopic dermatitis.

Meet Professor Seemal Desai

Professor Seemal Desai is a board-certified dermatologist in private and academic practice in Dallas, Texas and Clinical Assistant Professor in the Department of Dermatology at the University of Texas, Southwestern Medical Centre.

His clinical interest is in inflammatory skin diseases including atopic dermatitis and psoriasis. Professor Desai performs a variety of clinical trials and research in his practice. He also serves in multiple leadership positions within dermatology and the U.S. FDA (Food and Drug Administration).

What is the burden of atopic dermatitis for patients?

Without getting into the skin of a patient with atopic dermatitis, can you truly understand the severity of pruritis? Professor Steinhoff emphasises the many ways in which the burden of itching can impact an individual’s life – from serious limitations on everyday activities to life-changing psychological impact. You may identify with what you’ve have encountered in your own clinical practice as you hear about patients describing pruritis as the symptom for which they require most urgent help.

What are the underlying mechanisms of pruritus in atopic dermatitis?

Understanding the pathological mechanisms underpinning the experience of pruritis is vital to treating atopic dermatitis successfully. Listen to Professor Steinhoff provide a clear description of the multiple stimuli that activate neuronal pathways and contribute to the “itch-scratch cycle”. Hear him explain why, therefore, more than one approach to managing pruritis is required.

What is the itch-scratch cycle and what factors influence it?

The itch-scratch cycle is a serious challenge for patients, but is it always fully understood and clearly addressed? Ensure you appreciate the interplay between the dysfunction of the skin barrier in atopic dermatitis, the inflammatory factors at play, the role of central nervous system pathways, and the cause and effect of itching and scratching.

What are the remaining unmet needs and challenges to overcome when managing pruritus?

What more can we do to manage atopic dermatitis effectively and bring real therapeutic benefit to patients? Professor Steinhoff draws on longstanding expertise and experience to add insights, including for those with recalcitrant atopic dermatitis and pruritis. As he explores aspects of care from education and awareness right through to the realistic provision of treatments where they are needed, he provides us with a framework for priorities and practicalities moving forwards.

What are three key things to know about pruritus in atopic dermatitis and its treatment?

Listen to Professor Steinhoff focus attention on what he believes to be the most important things to appreciate when caring for those with atopic dermatitis. He emphasises a patient-centric approach, and provides vital advice to clinicians regarding management, self-education and the knowledge that needs to underpin treatment decisions. As we look to the future of atopic dermatitis care, Professor Steinhoff’s insights may help to ensure you are able to effectively provide help and relief for people living with this heterogenous condition.

Professor Martin Steinhoff

Professor Martin Steinhoff is Chairman of the Department of Dermatology and Venereology at Hamad Medical Corporation. He is also Director of the Dermatology Institute and the Translational Research Institute at Weill Cornell, New York and Qatar University, Qatar.

What notable emerging topical and systemic agents are currently in the pipeline?

Will the battle between biologics and small molecules benefit patients? Expand your knowledge on the pipeline of biologics and JAK inhibitors that are currently in development for moderate-to-severe atopic dermatitis, including tralokinumab, lebrikizumab, upadacitinib, and abrocitinib.

What are the types of JAK inhibitors and how do they differ?

A huge range of JAK inhibitors are currently known that inhibit the activity of the Janus kinase family of enzymes; JAK1, JAK2, JAK3, and TYK2. Further your knowledge of this class of drug, including their high degree of specificity and complex mechanism of action.

Have there been any studies into the efficacy and safety of JAK inhibitors?

Gain an overview of the range of the studies currently investigating the efficacy and safety of JAK inhibitors in moderate-to-severe atopic dermatitis, including abrocitinib, baricitinib, and upadacitinib. Also hear about the rapid onset of action and long-term benefits of this new class of molecules.

How could treatment strategies evolve in the future with the introduction of JAK inhibitors?

Atopic dermatitis is a complex disorder with large differences between phenotypes. Find out how biologics and JAK inhibitors have the potential to act as disease modifiers and give greater long-term control of the disorder.

Learn the three key updates you need to know in emerging treatments for moderate-to-severe atopic dermatitis

Short on time? Find out the essential updates in treatments for moderate-to-severe atopic dermatitis, such as JAK inhibitors, in this quick overview.

Meet Professor Thomas Bieber

Professor Thomas Bieber is a Professor of Dermatology and Allergy. He is Director of the Department of Dermatology and Allergy at the University of Bonn. He was board-certified in 1988 and draws on a huge amount of clinical and research experience within clinical dermatology and as a physician scientist.

His focus is on atopic dermatitis and understanding the heterogenicity and pathophysiology of this disorder. Professor Bieber also has a regulatory background and is involved in clinical development programmes and strategy. 

What impact can atopic dermatitis have on patients?

From interfering with work to negatively affecting sleep and mental health, see the profound impact on the lives of patients with atopic dermatitis.

What are the unmet needs in treating atopic dermatitis?

Learn about the significant unmet needs that remains in the treatment of atopic dermatitis in this short video with Professor Cork.

Current treatment options have limitations in terms of efficacy and adverse effects that can limit their use and the majority of patients surveyed with atopic dermatitis have described themselves as being not satisfied or only fairly satisfied with current available treatments¹.

What affects treatment compliance in atopic dermatitis?

Find out some of the challenges associated with TCS treatment.

Steroid phobia has been observed in over 80% of patients and parents^2,3, leading to an impact on treatment compliance³. Learn about the reasons why TCS treatment is associated with these fears.

What are the main limitations of topical corticosteroids and calcineurin inhibitors?

Discover the main limitations of using TCS and TCI for the treatment of atopic dermatitis.

Current guidelines recommend TCS and TCI for atopic dermatitis, but their safe and effective use requires adequate potency, sufficient dosage and correct application⁴. Their use is also limited by their treatment duration and adverse effects.

Meet Professor Michael Cork

Michael Cork is Professor of Dermatology in the Department of Infection, Immunity and Cardiovascular Disease at the University of Sheffield, United Kingdom. He is Consultant Dermatologist at Sheffield Children’s Hospital and Sheffield Teaching Hospitals.

His special interest is the treatment of atopic dermatitis and he sees a spectrum of mild, moderate and severe cases, including some of the most severe cases in the U.K. and internationally.

Unmet needs and treatment goals

Discover more about atopic dermatitis with Professor Amy Paller (biography) in the videos below, as she joins us to discuss various aspects of the disease including the pathophysiology, treatment, impact and unmet needs.

Is the treatment goal different when comparing paediatric and adult patients?

Dr Amy Paller discusses how atopic dermatitis can affect patients and the impact this has on their lives

Dr Amy Paller details the impact of atopic dermatitis on patients with different levels of disease severity

Hear Dr Amy Paller’s expert opinion on identifying the primary treatment goals of atopic dermatitis

Meet Professor Amy Paller

Professor Amy Paller, Professor and Chair of Dermatology at the Northwestern University School of Medicine, Chicago, U.S., is an expert in paediatric dermatology.

How is PDE4 involved in the pathophysiology of atopic dermatitis?

Professor Cork describes the central role of the PDE4 enzyme in regulating the release of a variety of inflammatory cytokines involved in the development of atopic dermatitis.

The pathophysiology of atopic dermatitis is complex and multifaceted, involving various elements such as skin barrier dysfunction, alterations to immune responses and environmental factors (Figure 1). Learn how elevated levels of PDE4 play a key role in the development of atopic dermatitis.

Figure 1: cAMP is present at high levels within a variety of cells with PDE4 regulating its breakdown. However, it has been shown that patients with atopic dermatitis display elevated levels of PDE4 in circulating inflammatory cells, resulting in a reduction in cAMP and an increase in the production of a variety of proinflammatory cytokines such as IL-4, IL-5 and IL-17. Adapted from: Purushothaman et al. 2018⁵. AC, Adenylyl cyclase; ATP, adenosine triphosphate; AMP, adenosine monophosphate; cAMP, cyclic adenosine monophosphate; IgE, immunoglobulin E; IL, interleukin; PDE4, phosphodiesterase-4.

Why is PDE4 an attractive therapeutic target?

Find out why PDE4 inhibitors have become a therapeutic target of interest, with Professor Cork, in this short video.

Limited choices in the range of topical treatments for atopic dermatitis has led to a great interest in developing new non-steroidal anti-inflammatory therapies. Topical PDE4 inhibitors have become an attractive therapeutic target utilising a unique mechanism of action (Figure 2).

Figure 2: Selective inhibition of PDE-4 prevents the degradation of cAMP to AMP. Increased levels of cAMP suppress the activity of NF-κB, NFAT and other pathways responsible for inflammatory cytokine production. This favourably suppresses the synthesis of inflammatory cytokines and subsequently arrests the development of atopic dermatitis via modulating the intracellular cAMP levels. (Adapted from: Oswald K 2017⁶). AMP, adenosine monophosphate; cAMP, cyclic adenosine monophosphate; IFN-y, interferon gamma; IL, interleukin; NFAT, nuclear factor of activated T-cells; NF-κB, nuclear factor-κB; PDE4, phosphodiesterase-4; TNF-α, tumour necrosis factor-α.

How do topical PDE4 inhibitors differ from oral options?

Learn about the differences between topical and oral PDE4 inhibitors and the benefits topical treatments can provide.

Targeted therapies that function at the site of action can provide significant advantages over oral forms of the same drug. Find out how topical and oral PDE4 inhibitors differ from each other in terms of bioavailability, systemic exposure and adverse events.

How is PDE4 currently being evaluated in clinical trials for atopic dermatitis?

Discover the trials that are currently on pause in Europe that will directly compare TCS with PDE4 inhibitors.

Phase three trials have provided significant efficacy and safety data for PDE4 inhibitors⁷. However, more research is needed to understand their effect on the skin. While COVID-19 is has put many clinical trials on pause, trials planned in Europe aim to compare the effect of TCS and PDE4 on atrophy of the epidermis.

Meet our expert Professor Michael Cork

Michael Cork is a Professor of Dermatology in the Department of Infection, Immunity and Cardiovascular Disease at the University of Sheffield, United Kingdom.