Tag: atopic dermatitis

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No One Type of Emollient is Best for Children with AD

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Atopic dermatitis
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A trial has directly comparing emollients found that no one type of emollient is better than another when it comes to atopic dermatitis (AD) in children.  The results from the study are published in The Lancet Child & Adolescent Health and British Journal of General Practice.

Emollients are recommended for the one in five children with AD.  Lack of research in this area means guidelines vary widely in what is recommended, which leads to confusion and waste.

In the study, 550 children with AD aged under 12 years were randomised to use one of four types of emollient (lotion, cream, gel or ointment) as their main emollient for 16 weeks. Parents completed diaries about their child’s AD for a year, and some were interviewed to gain an in-depth understanding of how they used the emollients and what they thought of them.  All children also had an independent examination of their skin.

Used alongside other AD treatments, there was no difference in effectiveness of the four types of emollient used in the study.  Skin reactions such as itching or redness were common with all emollienttypes.  Awareness of the different types of emollient was low, and users had different preferences based on how the emollients look and feel.  For example, some people liked how lotions quickly soaked in whereas others preferred the “barrier” provided by ointments.

Professor Matthew Ridd, a GP and study lead from Centre for Academic Primary Care at the University of Bristol, said: “A study of this type has been long overdue.  It has not been in the interest of the manufacturers to directly compare types of moisturiser in the way we have done in this trial.  Our findings challenge conventions about how often moisturisers need to be applied, which types are less likely to cause problems and which patients should be recommended certain types. For example, ointments are often suggested for more severe eczema, yet they were found to be no better.”

Professor Hywel Williams, consultant dermatologist and co-researcher at the University of Nottingham, explained: “Along with anti-inflammatory treatments such as topical corticosteroids, emollients are a really key part of treatment for childhood eczema, preventing flares and helping to soothe the skin and improving the quality of life for children and their carers.

“Our study shows that one size does not fit all, and points to the need for doctors to make parents aware of the different emollient types and to help them choose which one is mostly likely to work for them.  At last we have evidence that supports the saying, ‘The best moisturisers are the ones the patient will use.’”

Further work is needed to determine if these findings apply to adolescents and adults with AD, and people with other dry skin conditions.

Source: EurekAlert!

Categories : Diseases, Syndromes and ConditionsTags :

Obesity in Mice Causes AD Treatments to Backfire

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Mouse
Photo by Kanasi on Unsplash

In a new study published in Nature, researchers found that treatments that were effective for atopic dermatitis (AD) in lean mice actually worsened the condition in obese mice.

Tracking the development of AD in obese and lean mice, the researchers found that obese mice developed more inflammation and more severe AD. This increased inflammation was present even after obese mice lost weight. There were similar results in an experimental model of asthma, with obese mice developing more inflammation.

The researchers next looked in detail at immune cells called T cells in lean and obese mice with AD. Lean mice had more TH2 cells, a class of T cells known to play a role in the development of AD. Obese mice had more of a class of T cells called TH17. These cells trigger a different type of inflammation.

Similar trends were seen in blood samples taken from people. Markers of TH17 cell activity increased along with body mass index (BMI) in a database of serum collected from people with AD. Conversely, in samples from patients with severe asthma, TH2 cell activity decreased as BMI increased.

Drugs that block TH2 cell activity are used in the treatment of severe AD as well as asthma and other inflammatory conditions. The researchers tested antibodies to block TH2 cell activity in lean and obese mice with severe AD. While the antibodies reduced skin inflammation in lean mice as expected, they made the condition worse in obese mice. Analysis of immune cells suggested that blocking TH2 cell activity in the obese mice worsened other forms of inflammation.

Obese mice were also found to have less activity of peroxisome proliferator-activated receptor-γ (PPARɣ) in their TH2 cells. When lean mice were engineered to lack PPARɣ, their inflammatory response resembled that of obese mice.

Drugs that increase PPARɣ activity increase insulin sensitivity and are approved for the treatment of type 2 diabetes. The researchers found that giving one of these drugs to obese mice changed their inflammatory response to resemble that of lean mice. It also restored their sensitivity to the antibodies that block TH2 cell activity.

“Our findings demonstrate how differences in our individual metabolic states can have a major impact on inflammation, and how available drugs might be able to improve health outcomes,” said Dr Ronald Evans from the Salk Institute, who helped lead the work.

Source: National Institutes of Health

Categories : AllergiesTags :

Avoid Goat’s Milk Skin Products in Inflammatory Skin Conditions

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Photo by Robin Worrall on Unsplash

Individuals with inflammatory skin conditions should avoid using skincare products that contain food products such as goat’s milk, according to a series of case studies published in Clinical & Experimental Allergy. Such skincare products have been marketed to those with ‘sensitive skin’.

In children, milk allergy is one of the most common food allergies, but usually resolves in the first years of life. Adult-onset milk allergy is rare. In patients with inflammatory conditions of the skin such as atopic dermatitis, associations between the use of food allergen-containing skin products and systemic sensitisation to that foodstuff has been demonstrated for several foods. This is of concern, as food-containing skin products are commonly promoted as a safer and more ‘natural’ way of managing a variety of skin conditions. These are widely available for unprescribed purchase in pharmacies and supermarkets.

The present study reports on seven patients with inflammatory skin conditions who experienced anaphylaxis after ingesting goat’s or sheep’s milk or cheese products.  All of the patients had a history of using goat’s milk skin products to treat their skin conditions prior to the onset of their allergic reaction. Six of them had atopic dermatitis.

“Marketing of skin products derived from goat’s milk is extensive and targeted to patients with ‘sensitive skin’ who commonly have underlying inflammatory skin conditions,” the authors wrote. “Our findings provide novel evidence of the origins of adult-onset milk allergy and adds to the growing body of evidence that use of foodstuffs as therapy for inflammatory skin conditions can lead to the development of new food allergies.” 

Source: Wiley

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New Insights Into Atopic Dermatitis Yield Possible Therapy

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Atopic dermatitis (AD) is often thought of as an inflammatory disease that arises from a breakdown in the barrier function of the skin. Now a new study pinpoints a cascade of inflammatory signalling that precedes the appearance of skin ulcers, shedding light on the early stages of the condition and possible new drug targets.

The work, published in the journal Science Translational Medicine, was the result of a cross-school and cross-institutional collaboration among researchers.

“You have researchers in the dental school noticing a skin condition, broadening their work to the medical school and experts on computational systems biology,” said Professor Dana Graves, a co-corresponding author on the paper. “Without this interdisciplinary collaboration, that initial finding would not have gone anywhere.”

John Seykora, a co-corresponding author and professor of dermatology, agreed. “This shows one of the benefits of being part of a university with experts across fields,” he says. “Our dental school colleagues developed a mouse that manifested a particular skin phenotype, and the question was, What was this and did it resemble any disease we might know? And in the end it did, and it’s providing some novel insights into a very common skin condition in humans.”

The work began with an exploration of the role of inflammatory signalling in bone fracture healing in diabetes. A focus was on nuclear factor kappa-B (NF-kB), a master regulator of inflammatory responses. As part of that work, researchers developed a mouse model lacking an activator of NF-kB signalling, IKKB. The researchers noticed that these animals developed skin lesions as they became young adults.

“That was interesting to us because these ulcerations looked like an inflammatory event, but we had effectively turned off the activity of NF-kB, which should reduce inflammation,” said Prof Graves. “So this was a paradox.”

To better understand what was driving this response, they sought expertise in skin diseases from Prof Seykora. When they examined the mice, they noted several features quite similar to AD, “albeit the mouse version” said Prof Graves.

In particular, they noted skin thickening and an infiltration of certain types of white blood cells that are also seen in human AD. Delving deeper into how the loss of IKKB was driving these effects, the team performed single-celled RNA analysis combined with a new analysis method. The team learned that fibroblasts were the culprit, a major component of the skin’s dermis layer and typically thought to support the structural integrity of skin.

Though NF-kB typically promotes inflammation, here, decreased NF-kB activity was paradoxically leading to recruitment of immune cells and associated inflammation. Data from the team’s single-cell RNA analysis pointed to high activities of a protein transcription factor called CEBPB, as well as a signalling molecule, CCL11, “We worked out the mechanism in the mouse,” Prof Sekora said, “then showed that much of it applied in human tissue as well.”

When the researchers compared what they had seen in the mouse cells to skin samples from people with AD, they found similar patterns; CCL11 and CEBPB were both found at higher levels in the affected skin than in unaffected skin.

Testing a monoclonal antibody against CCL11 in mice tamped down the inflammatory response they had initially seen in animals lacking IKKB, suggesting that this could be a target to reduce AD-associated inflammation.

The researchers say the work also highlights a developing appreciation that fibroblasts play important roles in immune processes in the skin, indicating that they are important regulators of white blood cells.

AD  typically emerges in childhood, often manifesting along with asthma. Indeed, in the mice, too, the signalling abnormalities the researchers observed occurred in a period corresponding to the animals “childhood.” The group’s findings suggest that fibroblasts may be involved during this period in helping to establish appropriate immune signalling in the skin.

“We have viewed NF-kB as a factor that stimulates inflammation, but it could be that, during development, its activation might be important for maintaining homeostasis,” said Prof Graves.

The team’s next steps are to further explore NF-kB signalling in fibroblasts.

Source: University of Pennsylvania

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Atopic Dermatitis Linked to Range of Comorbid Conditions

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A comprehensive review has uncovered “clear evidence” of associations between atopic dermatitis (AD) and a range of comorbid conditions, which has informed updated clinical guidelines for AD. 

An expert panel reported on the results of a wide-ranging review in the Journal of the American Academy of Dermatology.  They found evidence linking AD to certain allergic, atopic, and immune-mediated conditions, as well as mental health problems, bone diseases, and skin infections. There is some evidence which supports associations between AD and substance use, attention deficit-hyperactivity disorder (ADHD), and some elements of metabolic syndrome. Less compelling evidence suggests AD has links to some cardiovascular conditions. There is inconclusive evidence for associations between adult AD and autism spectrum disorders, myocardial infarction, stroke, and metabolic syndrome. 

“Atopic dermatitis is one of several atopic diseases, meaning that there are internal sensitivities that can help drive the disease in the organ of choice, including asthma, allergic rhinoconjunctivitis, and food allergies, among others,” Dawn M.R. Davis, MD, co-chair of the guideline panel, told MedPage Today. “We always knew there was an association between atopic dermatitis and the other atopic diseases, but we lacked the evidence. Fortunately, because we’re getting more attention and more research is being performed in these areas, we now have data to back up our suspicions regarding the associations between atopic dermatitis and other atopic diseases.”

“Thanks to research by our colleagues, we discovered several other comorbidities that we did not expect, including skin diseases like alopecia areata and urticaria, as well as mental health conditions, including depression, anxiety, and substance use,” she continued. “We also have some evidence of associations with metabolic conditions, such as disorders of bone metabolism, and cardiovascular diseases.”

This review was conducted in concert with updating the American Academy of Dermatology clinical guideline on AD. The quantity and depth of data also warranted a separate guideline component for recognition of comorbidities associated with AD. The main goal was to increase awareness of the associations.

“The goal of this guideline is to plant a seed in the mind of providers and to empower and validate patients, so they can have a customised, individualised, robust discussion about how their particular circumstances relate to any of the risk factors,” said Dr Davis.

Key findings and statements in the guideline include:

  • The association between AD and asthma is well established, but the “atopic march” explanation remains unproven
  • “Clear evidence” of an association between AD and food allergy, but estimated prevalence of food allergy in adults with AD remains low
  • Epidemiologic studies “consistently show” an association between AD and alopecia areata, but there are limited data on severity of alopecia or treatment response
  • Analysis of four studies showed that AD doubles the odds ratio of depression though reasons for this are unclear
  • A “potential association” between AD and substance use/abuse (limited evidence)
  • Accumulating evidence suggests small associations between AD and hypertension, peripheral and coronary artery disease, congestive heart failure, and acute clinical events
  • A “small association” suggested between adult AD with obesity and dyslipidemia; however, limited data have pointed to a possible inverse association with diabetes
  • Several studies have shown associations with increased risk of osteoporosis and fracture in adults with AD, possibly linked by systemic inflammation.

“To date, research on AD-associated comorbidities has focused on identifying potential associations in epidemiologic studies,” the guideline authors wrote. “There is currently no conclusive evidence demonstrating that screening for comorbid conditions associated with AD improves patient outcomes. For the evidence of AD associations to be put into action, research is required on whether screening or management of these comorbidities among adults with AD beyond what is recommended for the general population is beneficial.”

Besides the comorbidities document, other documents will be published over two years which will address topical therapy, systemic treatment and phototherapy, and paediatric AD.

Source: MedPage Today

Categories : Diseases, Syndromes and Conditions New Compounds and TreatmentsTags :

An End to The ‘Therapeutic Drought’ in Atopic Dermatitis

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Source: NCI

The end of a longstanding “therapeutic drought” in atopic dermatitis (AD) is in sight as improved understanding of the pathogenesis and pathophysiology has stoked development of multiple drug candidates, according to a leading expert in the field.

“We did have treatments like cyclosporine, that are not specific as we know, and they are not treatments we can give our patients for long-term disease control,” said Emma Guttman-Yassky, MD, of the Icahn School of Medicine at Mount Sinai, during the Inflammatory Skin Diseases Summit.

She said that overcoming this drought was not easy, mostly because “we didn’t have enough understanding of the disease and its pathogenesis, really preventing therapeutic development for patients with atopic dermatitis,” she said.

New AD therapies built on the trail made for psoriasis treatment, starting with basic studies that produced insights into pathogenesis, leading to hypotheses that eventually could be tested in clinical trials, she said. Progress was accompanied by many failures in early stages of therapeutic development in psoriasis.

“One failure that I remember very vividly from psoriasis was the failure of interferon-gamma targeting,” Dr Guttman-Yassky recounted. “In atopic dermatitis, we also had our share of this type of failure, but these failures really helped shape therapeutic directions for all the diseases we are now targeting, including atopic dermatitis.”

This rocky development has led to recognition that AD is a complex disease involving multiple pathogenetic components, including barrier dysfunction, immune abnormalities, disruption of the dermal microbiome, and the peripheral and central nervous systems that play a central role in itch and other disease manifestations.

“Of all the major components involved in AD pathogenesis, immune targeting is the most tractable,” said Dr Guttman-Yassky. “Immune abnormalities are the most important because they perpetuate the disease phenotype of atopic dermatitis, from the nonlesional skin to acute disease and chronic lesions.”

In contrast to psoriasis, AD is a more heterogeneous disease with multiple clinical phenotypes that correlate with differences in immune polarisation and barrier dysfunction. All of the phenotypes exhibit activation of the type 2 inflammatory pathway as a common feature. Across the spectrum of clinical phenotypes, additional cytokine targeting may be required to achieve disease control.

Understanding that AD arises from systemic inflammation has also helped therapy development. Several studies have suggested that, compared to psoriasis, AD is associated with higher levels of immune activation. Blood samples of patients with AD have shown increased levels of activated T cells, circulatory cytokines, and cardiovascular markers.
The accumulation of new insights into AD pathogenesis added no fewer than a dozen viable therapeutic candidates to the pipeline. Dupilumab (Dupixent) led the way in providing the proof of principle that Th2-specific targeting reverses key pathogenetic factors that drive the disease process in AD.

Dr Guttman-Yassky pointed out how targeting Th2 inflammation with dupilumab led to reversal of barrier defects and lichenisation typical of AD as early as 4 weeks, and that by 16 weeks lesional and nonlesional skin looked similar. Furthermore, markers of epidermal hyperplasia and proliferation were “completely wiped out.”

Dr Guttman-Yassky highlighted several key classes of AD drug candidates with potential to build on the success of targeting inflammation: Interleukin-13 inhibition, OX40 inhibition and JAK/STAT inhibition, which showed promising results.

“With these types of response rates, our treatment goals for our patients are evolving,” said Dr Guttman-Yassky.

Source: MedPage Today

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Discovery of Cell Type Linked to Skin Conditions

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Researchers have found a cell type in human skin that contributes to inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis (PSO). Their study findings were published in the Journal of Experimental Medicine. The team hails from A*STAR’s Singapore Immunology Network (SIgN).

Chronic inflammatory skin diseases such as AD and PSO are characterised by the presence of an activated T cell subtype which secretes pro-inflammatory cytokines in the skin. This immune dysregulation mediated by T cells is central to the pathogenesis of a wide range of inflammatory skin diseases. Thus, understanding the factors modulating T cell priming and activation in healthy and diseased skin is key to developing effective treatments for these diseases.

Recently, a single-cell RNA sequencing (RNA-seq) approach has been used to analyse immune cells in human skin, including dendritic cells (DCs) and macrophages, which are cells that can T cell activation. To tease out the role of DCs and macrophages in chronic inflammatory skin diseases, the team used a combination of complex approaches to yield an unbiased profile/ landscape of DCs and macrophages, and to describe their distinct molecular signatures and proportions in skin lesions of AD and PSO patients.

The researchers found an increase in the proportion of CD14+ DC3s in PSO lesional skin, where they were one of the major cell types co-expressing IL1B and IL23A, two cytokines essential for PSO pathogenesis. This finding suggests that targeting CD14+ DC3 might represent a novel therapeutic option in the treatment of PSO, and demonstrates the potential for the single-cell myeloid cell landscape database to provide important insights into skin biology in health and disease.

Last author Dr Florent Ginhoux, Senior Principal Investigator, SIgN said: “The findings from this study are significant as it will allow the design of new strategies to target or modulate myeloid cell populations for better health outcomes for patients of atopic dermatitis and psoriasis.”

“The roles of antigen-presenting cells in the development of inflammatory skin diseases remain unclear. This study clearly revealed the functions of each antigen-presenting cell subset, which is very informative and valuable to understand the pathogenesis of atopic dermatitis and psoriasis. We expect that this study will lead to the design of new treatment for refractory inflammatory skin diseases.” said Prof Kenji Kabashima, Adjunct Principal Investigator from SIgN and SRIS.

Source: EurekAlert!

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Abrocitinib Promising in Teen Atopic Dermatitis

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Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health

Following treatment with the investigational oral Janus kinase (JAK) inhibitor abrocitinib plus topical therapy, teenagers with moderate or severe atopic dermatitis (AD) showed significant improvement to placebo, according to a new study published in JAMA Dermatology.

Up to 20% of children and adolescents are affected by AD, which has an adverse impact on QoL, academic performance, and social relationships, as well as the QoL of caregivers. Subcutaneous dupilumab is safe and effective in moderate-to-severe AD in adolescents, but there is a lack of an oral option, they said.

Nearly half of the patients had clear or almost clear skin by clinician assessment (IGA), and about 70% of patients treated with either of two doses of the JAK inhibitor had at least 75% improvement in the Eczema Area and Severity Index (EASI-75). In contrast, a fourth of patients who received placebo in addition to topical therapy met the clinician assessment outcome and about 40% met EASI-75 criteria.

Abrocitinib, a JAK-1-selective inhibitor, had already shown to be tolerable and effective in adults. The present trial included 285 patients aged 12 to 17, with coprimary endpoints being an IGA score of 0/1 with at least a two-grade improvement from baseline, plus an EASI-75 response, with both outcomes assessed at 12 weeks. Secondary endpoints included improvement in pruritis.

An IGA 0/1 response was seen in 46.2% of patients treated with abrocitinib 200 mg and 41.6% of those assigned to abrocitinib 100 mg, compared to 24.5% in the placebo group. The proportion of patients who met EASI-75 response criteria was 72% with abrocitinib 200 mg, 68.5% with abrocitinib 100 mg, and 41.5% with placebo. Significant improvement was seen in pruritis compared to placebo, showing an improvement in pruritis. The researchers noted that improved indicators could lead to better sleep and QoL indicators.

AE rates were 62.8% with the higher dose of abrocitinib, 56.8% with the lower dose, and 52.1% in the placebo group, with nausea occurring more often with abrocitinib 200 mg than with abrocitinib 100 mg (18.1% vs 7.4%).

These results suggest abrocitinib has great potential for treating teenage AD, said John C. Browning, MD, of Texas Dermatology and Laser Specialists in Dallas. Current there are no JAK inhibitors indicated for AD, and an oral option is very exciting he to MedPage Today via email. “Not everyone responds to current systemic therapies, so there is a definite need for new treatments.”

“I think more teens will be open to trying an oral option, but they will need to be committed to taking it every day,” he said, adding that compliance is an issue. “Both abrocitinib and dupilumab are effective, so there is not a tradeoff in going from injections to oral therapy.”

Source: MedPage Today

Categories : Diseases, Syndromes and Conditions Mental HealthTags :

Severe Atopic Dermatitis Threatens Mental Health

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Photo by Romina Farías on Unsplash
Photo by Romina Farías on Unsplash

A US study showed that adults with atopic dermatitis (AD) had a higher burden of disease than those with other chronic diseases. Even mild dermatitis can negatively affect quality of life (QoL), increasing risk of anxiety, depression, and suicide.

Persistent itching and skin pain can disrupt sleep, leading to poor work or study performance. In moderate to severe disease, oozing, crusting lesions can lead to stigmatisation social isolation. More adults are affected than previously thought, with some 16.5 million adults in the US estimated to have AD.

In a study of 1278 patients using the US web-based Growth from Knowledge (GfK) panel, 60.1% had mild disease, 28.9% had moderate AD, and 11% had severe AD. Patients with more severe disease had higher scores on the dermatology life quality index and on the hospital anxiety and depression scale (HADS) when compared with controls.

This indicates “a worse impact on quality of life and an increased likelihood of anxiety or depression,” the researchers wrote in the Journal of Investigative Dermatology. “Our study confirms the high prevalence and disease burden of atopic dermatitis in this population.”

Quality of life threatened
A pair of studies in patients from the GfK panel reinforce these findings. The first, with 602 patients, showed that AD carried a “profound” disease burden, based on a comparison of patient-oriented AD measures between patients with and without AD. Those with moderate and severe AD had lower mean mental health scores compared with those who had mild disease, and lower QoL compared with patients with other chronic disorders.

“We recommend that clinicians incorporate QoL assessments in clinical practice to determine disease burden, identify patients requiring step-up treatment of their skin disease, and potentially screen for patients with mental health disturbance,” wrote Jonathan I Silverberg, MD, PhD, MPH, of George Washington University, and colleagues in the Annals of Allergy, Asthma and Immunology.

A subsequent study in 2137 patients from the GfK Knowledge Panel found that 40% of patients with AD had a higher prevalence of anxiety or depression in the previous 12 months compared with 17.5% of adults without AD. The researchers concluded that anxiety and depression were driven primarily by disease severity, and were heavily underdiagnosed.

Breaking the ‘vicious cycle’
AD can be life-threatening in some patients, warned the authors of a systematic review and meta-analysis of AD studies. The combination of pruritus, visible skin lesions, social isolation, depression, and anxiety likely sets up a “vicious cycle,” according to the authors.

This “may result in suicidal ideation, suicide attempts, and even completed suicide,” they reported in the Journal of the American Academy of Dermatology.

The investigators found a positive and significant association between AD in adulthood and depression, anxiety, and suicidal ideation, regardless of where the patients lived. And while only a few studies examined the risk of completed suicide, the majority showed a positive association, the authors said. A positive association between AD and depression in children was also identified.

They advised that “depression, anxiety, and suicidal ideation should be considered by doctors when treating patients with AD,” adding: “Because AD disease improvement appears to reduce these risks, this should be a priority.”

Better systemic and topical AD therapies are improving the QoL of patients. “It is important to recognise that improvement of AD often results in improvements in symptoms of depression and anxiety, as these mental health symptoms are caused or worsened by the AD,” Dr Silverberg told MedPage Today. “We already have data for dupilumab and the JAK inhibitors that show improvements of HADS scores and other patient-reported outcome measures of mental health.”

Robert Sidbury, MD, MPH, of the University of Washington School of Medicine in Seattle said, “relatively recent literature suggests screening for depression is particularly important for kids with AD, especially those with severe disease.”

AD affects children of all ages, including the very young, and more than 50% of children with AD are diagnosed by age 1 year, he noted.”Dupilumab has been the most effective new available therapy to date by far,” Dr Sidbury told MedPage Today. “Pipeline drugs, particularly the JAK inhibitors like upadacitinib  show tremendous promise.”

Source: MedPage Today

Categories : New Compounds and Treatments Skin ConditionsTags :

New JAK1 Inhibitor Abrocitinib Effective in Atopic Dermatitis

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A phase III trial showed that a new oral Janus kinase 1 (JAK1) inhibitor, abrocitinib, bettered placebo, at higher doses, also outperformed dupilumab in treating signs and symptoms of atopic dermatitis.

More patients on the higher dose of abrocitinib had an Eczema Area and Severity Index 75 (EASI-75) response (75% improvement from baseline) as compared with the other three randomised groups, reported Hernan Valdez, MD, of Pfizer in New York City, and colleagues.

“In the JADE COMPARE trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo on the basis of IGA and EASI-75 responses at weeks 12 and 16,” the authors stated. “The 100-mg dose of abrocitinib was not significantly different from dupilumab with respect to the three key secondary endpoints of the trial.”

“The 200-mg dose of abrocitinib was superior to dupilumab with respect to itch response at week 2 but not to an EASI-75 response at week 16; no conclusion could be drawn regarding the difference between the 200-mg dose of abrocitinib and dupilumab with respect to an IGA response… . Longer and larger trials are necessary to determine the efficacy and safety of abrocitinib and to compare it with other JAK inhibitors and with biologic agents used for the treatment of atopic dermatitis,” they added.

Several oral JAK inhibitors besides abrocitinib being clinically evaluatied for AD. According to the authors, targeting JAK1 results in inhibition of signaling by interleukin (IL)-4, IL-13, and other cytokines involved in AD. However, there is a lack of data on head-to-head trials of JAK inhibitors.

Despite the very positive reception of JAK inhibitors for the treatment of AD, there have been some studies which raised safety concerns. Tofacitinib, for example, has been associated with a higher rate of malignancies and major adverse cardiovascular events.

In this phase III trial, 838 patients with moderate or severe AD were randomised to abrocitinib 100 mg or 200 mg, dupilumab, or placebo. The trial had two primary endpoints: investigator’s global assessment (IGA) response at week 12 and EASI-75 response at week 12. Both endpoints were compared versus placebo. Secondary analyses included comparisons of itch response at week 2 versus placebo and dupilumab and IGA and EASI-75 responses versus placebo at week 16.

More patients on either of the two doses of abrocitinib had IGA responses at week 12 compared to placebo. The proportion of patients with an EASI-75 response at 12 weeks was 70.3% with abrocitinib 200mg, 58.7% for abrocitinib 100mg, 58.1% for dupilumab, and 27.1% for placebo. All treatment groups performed significantly better than placebo.

At week 2, 49.1% of patients had itch response with the higher dose of abrocitinib, 31.8% with the lower dose, 26.4% with dupilumab, and 13.8% with placebo. The 200-mg abrocitinib group was superior to dupilumab. 

Adverse events (AEs) occurred more often with 200-mg abrocitinib as compared with the other three groups (61.9% vs 50.0% to 53.4%), the most common of which was nausea.

Source: MedPage Today

Journal information:  Bieber T, et al “Abrocitinib versus placebo or dupilumab for atopic dermatitis” N Engl J Med 2021; DOI: 10.1056/NEJM0a2019380.