Daily Archives: October 5, 2021

Topical application of imiquimod (IMQ), a TLR7/8 ligand and potent immune activator, can induce and exacerbate psoriasis, a chronic inflammatory skin disorder. Recently, a crucial role was proposed for the IL-23/IL-17 axis in psoriasis. We hypothesized that IMQ-induced dermatitis in mice can serve as a model for the analysis of pathogenic mechanisms in psoriasis-like dermatitis and assessed its IL-23/IL-17 axis dependency. Daily application of IMQ on mouse back skin induced inflamed scaly skin lesions resembling plaque type psoriasis. These lesions showed increased epidermal proliferation, abnormal differentiation, epidermal accumulation of neutrophils in microabcesses, neoangiogenesis, and infiltrates consisting of CD4(+) T cells, CD11c(+) dendritic cells, and plasmacytoid dendritic cells. IMQ induced epidermal expression of IL-23, IL-17A, and IL-17F, as well as an increase in splenic Th17 cells. IMQ-induced dermatitis was partially dependent on the presence of T cells, whereas disease development was almost completely blocked in mice deficient for IL-23 or the IL-17 receptor, demonstrating a pivotal role of the IL-23/IL-17 axis. In conclusion, the sole application of the innate TLR7/8 ligand IMQ rapidly induces a dermatitis closely resembling human psoriasis, critically dependent on the IL-23/IL-17 axis. This rapid and convenient model allows further elucidation of pathogenic mechanisms and evaluation of new therapies in psoriasis.

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If youre one of the roughly 7.5 million Americans living with psoriasis, you know it isnt exactly fun. While you may go for years without symptoms, when you have a psoriasis flare-up, it can be everything from uncomfortable to downright distressing. And part of what makes it such a difficult condition to deal with is because you never know when a flare-up might occur and what could cause it. One biggie thats thought to cause flare-ups is food.

Certain types of foods appear to trigger or worsen psoriasis symptoms, and others may actually help tame signs of psoriasis, but everyone is different and foods that trigger flare-ups for some may not affect others with psoriasis, so pay attention to what seems to personally affect you, says Annie Gonzalez, M.D., F.A.A.D, a board-certified dermatologist at Riverchase Dermatology in Miami, Florida.

To help, we rounded up the best foods to eat if you have psoriasis and ones you should try to avoid, if you can.

Psoriasis is a skin disease with an unclear cause whats known is that it happens when the immune system goes into overdrive, triggering inflammation and inflammatory skin symptoms due to that overactivity that speeds up skin cell growth. The most common type of psoriasis (80%-90% of people with psoriasis have this kind) is called plaque psoriasis, characterized by patches of thick, raised skin that may itch and be red or partially covered in silvery-white scales; these patches can develop anywhere but tend to appear on the elbows, knees, lower back and scalp. Other ways a psoriasis flare-up may manifest is as tiny, salmon-to-pink colored bumps; smooth, raw-looking red patches around skin creases like the armpits; red, swollen skin dotted with pus-filled bumps; and as nail issues like tiny dents, rough crumbling nails, discoloration or lifting of the nail.

Weather, stress, infections (such as strep throat), smoking or secondhand smoke and certain medications, like those to treat high blood pressure are some common psoriasis flare triggers. Food is also thought to play a role in prompting of psoriasis flares. Specifically, inflammatory foods (a.k.a. foods that cause inflammation in the body) are thought to be common culprits, but more research in this area needs to be done. My advice is, if you notice your skin gets worse after eating certain foods, avoid and stop eating them to see what happens, says Dr. Gonzalez.

In general, eat a well-balanced diet thats high in fruits and vegetables and healthy fats this mix ensures youre consuming an array of nutrients and antioxidants that help prevent and reduce inflammation that could trigger a psoriasis flare-up.

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Fruits and veggies may reduce inflammation because theyre high in antioxidants and vitamins, which have been also been related to lower levels of oxidative stress and inflammation, says Gonzalez. Aromatics like onions and garlic are also smart to incorporate; they contain quercetin, an anti-inflammatory antioxidant.

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Heart-healthy fats and omega-3 fatty acids have anti-inflammatory properties that can help decrease inflammation to alleviate or prevent symptoms.

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Many of these flavor enhancers are also thought to play a role in taming inflammation.

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Foods to avoid if you have psoriasis:

Remember: Not every food on this list will definitely trigger a psoriasis flare-up, but if you do notice that your diet is affecting your skin, these inflammatory foods might be to blame, and cutting back or eliminating may help. Foods that have been known to trigger psoriasis include eggs, red and processed meat, canned produce, and packaged or processed foods, Gonzalez says.

These types of proteins tend to be high in saturated fat, an inflammation raiser and processed meats often contain preservatives, additives, and other flavor enhancers that may have a similar affect.

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These types of products often contain various inflammation triggers, such as added sugar, trans fat, preservatives, sodium and flavorings.

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Some research suggests that people with psoriasis may also be sensitive to gluten, a protein found in wheat, barley, and rye, possibly due to similar genetic and other inflammatory markers that affect people with Celiac disease.

Avoid or limit:

Everyone is different and different bodies will react differently to certain foods. Try jotting down which foods seem to impact your skin, so you can keep track and have that information on hand to consult with your doctor about your diet.

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Psoriasis Diet: What It Is, Best Foods to Eat and Food You Should Avoid - GoodHousekeeping.com

The main factors behind the vaccine hesitancy are the potential adverse effects post-vaccination and effect on their autoimmune conditions, as well as lack of trial data, an analysis shows.

Individuals with psoriasis are hesitant to get the COVID-19 vaccination, but there is no differential risk of respiratory tract infection (RTI) and serous infection (SI), the results of 2 new studies presented at the European Academy of Dermatology and Venereologys (EADV) 30th Congress show.

Our analysis reveals no differences in risk of respiratory tract infections between biologics, including the newer IL-17 and IL-23 inhibitors, in a prospective psoriasis patients cohort. In addition, our preliminary results suggest that biological treatments do not impact psoriasis patients susceptibility to COVID-19 infections, although this needs to be further investigated, Lara van der Schoot of the department of dermatology at Radboud University Medical Center in Nijmegen, Netherlands, said in a statement.

These findings provide key clinical value and will help to guide patient decisions with regard to psoriasis treatment options and choice, she said.

Results from the first study show that COVID-19 vaccine hesitancy was driven by safety concerns and worries about aggravation of the individuals underlying conditions, as well as a lack of trial data.

Additionally, investigators said that individuals had no information on the effect of the COVID-19 vaccine on biologic therapy in immunocompromised individuals.

Treatments for psoriasis are often associated with an increase in infections, so in the second study, investigators examined the effect of biological therapies on the risk for RTI and SI, including COVID-19.

Investigators found that there was no differential risk of RTI among included biologics adalimumab, etanercept, guselkumab, infliximab, ixekizumab, secukinumab, and ustekinumab, and no association with serious infections.

In the first unique study, investigators collected real-world data from social media to minimize limitations from traditional hospital surveys.

Investigators gathered 10,922 social media posts between January and March 2021. They included individuals in France, Germany, Spain, the United States, and the United Kingdom, using pre-defined words, which were narrowed down to 625 posts that were manually analyzed.

The second study included 714 individuals with psoriasis, with 1325 treatment episodes from the BioCAPTURE registry, 2224 with RTI and 63 with SI.

Just 1.3% of RITs were reported to be serious.

Reference

Safety analysis of biologics and highlighting vaccine hesitancy: real-world data shines a light on the impact of COVID-19 on psoriasis patients. EurekAlert. News release. September 30, 2021. October 1, 2021. https://www.eurekalert.org/news-releases/929887

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Individuals With Psoriasis Are Hesitant to Get Vaccinated for COVID-19 - Pharmacy Times

Treatment with tapinarof 1%, a nonsteroidal topical cream in clinical development, was associated with durable control of plaque psoriasis in a 52-week phase 3 trial presented as a latebreaker at the European Academy of Dermatology and Venereology (EADV) 2021 Annual Meeting.

The drug has several unique features with meaningful clinical differences from other topical psoriasis therapies, according to Linda Stein Gold, MD, director of dermatology clinical research, Henry Ford Health System, Detroit, Michigan.

"The currently available nonsteroidal topical therapies are typically associated with significant irritation. We did not see that with tapinarof," said Gold. This is one of several reasons she believes this drug will be a valuable addition if it receives regulatory approval.

Tapinarof is a small-molecule aryl hydrocarbon receptor (AhR) modulating agent. AhR is widely expressed in immune cells, including macrophages, mast cells, and antigen-presenting cells. It is believed that modulation of AhR signaling by tapinarof reverses immune dysregulation that is involved in the formation of psoriatic lesions.

The newly presented PSOARING 3 data with tapinarof 1% build on the data from the 12-week PSOARING 1 and PSOARING 2 trials, which were released in August 2020 but have yet to be published.

The primary endpoint in both of the 12-week trials, each of which enrolled about 500 patients with plaque psoriasis, was a Physician Global Assessment (PGA) score of 0 (clear) or 1 (almost clear). Relative to a placebo response rate of about 6% in both trials, the proportion of patients who achieved scores of 0/1 with tapinarof 1% was 35.4% and 40.2% in the PSOARING 1 and PSOARING 2 trials, respectively (P < .0001 vs placebo in both studies).

For the key secondary endpoint of 75% improvement in the Psoriasis Area and Severity Index (PASI75), the relative advantage for tapinarof over placebo was similar. The results were highly statistically significant (P < .0001) in both of the 12-week trials.

More than 90% of the patients who participated in PSOARING 1 and PSOARING 2 and were eligible for the open-label PSOARING 3 extension trial, according to Gold.

For the 79 patients with a score of 0 at the time of enrollment, tapinarof 1% was reapplied only if the PGA score reached 2 during the course of the study. For the 680 patients who entered with a PGA score of 1, once-daily applications of tapinarof 1% cream were maintained until a PGA score of 0 was achieved.

In the outcome analysis, response was defined as the proportion of patients with an initial PGA score of 2 who achieved PGA 0. A remittive effect was defined as duration of a PGA score of 0 or 1 while off therapy after achieving a PGA score of 0. Durability of response was defined as the proportion of patients who achieved a PGA sore of 0 or 1 at least once during the study while on therapy. This last outcome provided a test of tachyphylaxis.

"Overall, 40.9% of patients achieved complete disease clearance at least once during the trial, and 58.2% who entered the study with a PGA score of 2 or higher achieved a PGA score of 0 or 1," Gold reported.

For the 79 patients who entered PSOARING 3 with a PGA score of 0 and were off treatment, the median duration of a remittive effect was 115 days. For the patients who entered the trial with a higher PGA score but who achieved a score of 0 during the study (312 patients), the mean remittive effect after discontinuing therapy was 130 days.

There was no evidence of tachyphylaxis. Rather, "there was no loss of effect despite intermittent therapy observed over the course of the trial," Gold reported.

The most common treatment-emergent adverse events in PSOARING 3, as in the previous PSOARING studies, were folliculitis, which was observed in 24.0% of patients; contact dermatitis, which occurred in 5.9% of patients; and headache, which was reported in 2%. Rates of study drug discontinuations for folliculitis and contact dermatitis were 1.2% and 1.4%, respectively. Headache did not lead to any study discontinuations.

Calling tapinarof a "first-in-class nonsteroidal," Gold suggested that this is likely to be a useful adjunctive therapy for psoriasis control. It avoids the adverse events associated with long-term topical steroid use, and its tolerability might be particularly attractive for use in sensitive areas.

"This is likely to be very useful in patients who are looking for a topical therapy for skin folds or the face, where there is a need for well-tolerated topical treatments," Gold said.

There are a lot of reasons to be positive about a new, well-tolerated topical agent for psoriasis, particularly as an alternative to topical steroids, agreed Adam Friedman, MD, director of translational research and professor and chair of the Department of Dermatology at George Washington School of Medicine and Health Sciences, Washington, DC. He considers the data with tapinarof promising in general, but he also likes any new, effective topical psoriasis therapy.

"Patients and physicians are always hungry for new options, especially psoriasis patients, given many have 'been there and done that' with topical steroids," Friedman said.

"Topical steroids are not irritating, but long-term use beyond recommended dosing can lead to skin thinning, lightening, tachyphylaxis, and, if really abused, HPA [hypothalamic-pituitary-adrenal]axis suppression and adrenal insufficiency," he observed.

A topical therapy with a durable effect is particularly intriguing.

"The other issue with topical steroids is that psoriatic plaques return rather easily after stopping. The data I have seen with tapinarof show more sustainability after cessation, owing to its mechanism of action," Friedman said. Rather than its potential for application to sensitive areas, such as the face, the durability "to me is more interesting," he said.

He suspects that, owing to "the incurable steroid phobia that haunts many of our patients," an effective nonsteroidal topical option is also likely to lead to better compliance with topical treatment over time.

"A well-tolerated nonsteroidal topical drug will probably find an important place in the future management of chronic inflammatory diseases," Marius-Anton Ionescu, MD, PhD, a dermatologist at the Hpital Saint Louis, Paris, France, said in an interview. He referred to the positive effects of treatment with tapinarof in clinical trials in adults with atopic dermatitis, in addition to psoriasis.

Tapinarof 1% is also being investigated in a phase 3 study involving patients with moderate to severe atopic dermatitis. In that study, patients are as young as age 2 years. The drug is under review at the US Food and Drug Administration for the plaque psoriasis indication in adults.

Gold has financial relationships with Arcutis, Amgen, Bristol-Myers Squibb, Eli Lilly, Leo Pharma Ortho Dermatologic, UCB, and Dermavant Sciences, which is developing tapinarof and is provided funding for the PSOARING 3 trial. Friedman reports financial relationships with Amgen, Biogen, Encore, Galderma, GlaxoSmithKline, IntraDerm, Johnson & Johnson, Nerium, Novartis, Oculus, Onset, Pfizer, Sanova, and Valeant Pharmaceuticals. Ionescu has been a speaker or investigator (honoraria) for Celgene, Novartis, Lilly, and Uriage Cosmetics.

European Academy of Dermatology and Venereology (EADV) 2021 Annual Meeting: Abstract 2860. Presented September 30, 2021.

Ted Bosworth is a medical journalist based in New York City.

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Novel Topical Found Effective for Psoriasis in 52-Week Study - Medscape

WESTLAKE VILLAGE, Calif., Oct. 04, 2021 (GLOBE NEWSWIRE) -- Arcutis Biotherapeutics, Inc.(Nasdaq: ARQT), a late-stage biopharmaceutical company focused on developing meaningful innovations in immuno-dermatology to address the urgent needs of patients living with immune-mediated dermatological diseases and conditions, today announced it has submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for roflumilast cream for the treatment of mild-to-severe plaque psoriasis.

Roflumilast cream (ARQ-151) is a once-daily topical formulation of roflumilast, a highly potent and selective inhibitor of phosphodiesterase type 4 (PDE4), an enzyme that drives overactive immune responses. In clinical trials, roflumilast cream demonstrated robust efficacy coupled with favorable safety and tolerability that, if approved, would enable chronic use across the body, without many of the local tolerability issues associated with alternative treatments.

Today is a critical milestone for Arcutis in our efforts to bring innovative treatments to dermatologists and their patients, and is a reflection of our deep dermatology expertise, said Frank Watanabe, President and CEO of Arcutis. Individuals with plaque psoriasis currently do not have topical treatment options that offer a combination of good tolerability and the ability to be used for long periods of time, and that can be used on all parts of the body. If approved, roflumilast cream will be the first and only topical PDE4 inhibitor approved for psoriasis and an important non-steroidal treatment option for the millions of individuals struggling with plaque psoriasis. I want to thank the Arcutis team, as well as the clinical investigators, patients, and partners, for helping us reach this important milestone.

Psoriasis is a common, non-contagious, immune-mediated skin disease that affects more than 3% of the U.S. population. The majority of patients develop plaques, or raised, red areas of skin covered with a silver or white layer of dead skin cells. Psoriatic plaques are often itchy and sometimes painful, and can appear on any area of the body. Plaques in certain anatomical areas present particular treatment challenges, including the face, elbows and knees, scalp, and areas where two skin areas may touch or rub together.

Topical treatments are the mainstay of therapy for the vast majority of psoriasis patients, particularly those with mild-to-moderate disease, as well as many moderate-to-severe patients who use topicals in combination with other treatments. However, existing topical treatments often force physicians and patients to make difficult trade-offs between tolerability and long-term use, requiring the use of multiple products or complicated treatment schedules. Roflumilast cream has been designed to address the challenges posed to dermatologists and patients by existing topical therapies and aims to simplify the overall management of plaque psoriasis.

Arcutis submission is supported by positive data from Arcutis pivotal Phase 3 program. The DERMIS 1 and DERMIS 2 (Trials of PDE4 inhibition withRoflumilast for theManagement of plaque PsoriasIS One and Two) were identical Phase 3 randomized, parallel, double-blind, vehicle-controlled, multi-national, multi-center studies to evaluate the safety and efficacy ofroflumilast cream 0.3%. Roflumilast met its primary endpoint and had an IGA Success rate of 42.4% compared to a vehicle rate of 6.1% (P<0.0001), and 37.5% compared to a vehicle rate of 6.9% (P<0.0001), in DERMIS 1 and 2 respectively. Roflumilast cream 0.3% also demonstrated statistically significant improvements over vehicle on key secondary endpoints, including on Intertriginous IGA (I-IGA) Success, Psoriasis Area Severity Index-75 (PASI-75), reductions in itch as measured by the Worst Itch-Numerical Rating Scale (WI-NRS), and patient perceptions of symptoms as measured by the Psoriasis Symptoms Diary (PSD). In trials, roflumilast cream was generally well-tolerated with a favorable safety and tolerability profile.

About Roflumilast CreamRoflumilast Cream is a topical cream formulation of a highly potent and selective PDE4 inhibitor, roflumilast. Roflumilast has been approved by the U.S. Food and Drug Administration (FDA) for oral treatment to reduce the risk of exacerbations of chronic obstructive pulmonary disease (COPD) since 2011. Roflumilast has shown greater potency (25- to 300-fold) than the two other FDA-approved PDE4 inhibitors. PDE4 is an intracellular enzyme that increases the production of pro-inflammatory mediators and decreases production of anti-inflammatory mediators and has been implicated in a wide range of inflammatory diseases including psoriasis, eczema, and COPD. PDE4 is an established target in dermatology, and other PDE4 inhibitors have been approved by the FDA for the topical treatment of atopic dermatitis or the systemic treatment of plaque psoriasis.

About ArcutisArcutis Biotherapeutics, Inc. (Nasdaq: ARQT) is a medical dermatology company that champions meaningful innovation to address the urgent needs of patients living with immune-mediated dermatological diseases and conditions. With a commitment to solving the most persistent patient challenges in dermatology, Arcutis harnesses our unique dermatology development platform coupled with our dermatology expertise to build differentiated therapies against biologically validated targets. Arcutis dermatology development platform includes a robust pipeline with multiple clinical programs for a range of inflammatory dermatological conditions, with one NDA submission now under review with the FDA and three Phase 3 clinical data readouts anticipated by the end of 2022. The companys lead program, topical roflumilast, has the potential to advance the standard of care for plaque psoriasis, atopic dermatitis, scalp psoriasis, and seborrheic dermatitis. For more information, visitwww.arcutis.comor follow Arcutis on LinkedIn and Twitter.

Forward-Looking StatementsThis press release contains "forward-looking" statements, including, among others, statements regarding the potential for roflumilast to be approved for the treatment of adults and adolescents with plaque psoriasis, the potential to use roflumilast cream over a long period of time, or chronically, and the potential for roflumilast to revolutionize the standard of care in plaque psoriasis and other inflammatory dermatological conditions. These statements involve substantial known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements and you should not place undue reliance on our forward-looking statements. Risks and uncertainties that may cause our actual results to differ include risks inherent in the clinical development process and regulatory approval process, the timing of regulatory filings, and our ability to defend our intellectual property. For a further description of the risks and uncertainties applicable to our business, see the "Risk Factors" section of our Form 10-K filed with U.S. Securities and Exchange Commission (SEC) on February 16, 2021, as well as any subsequent filings with the SEC. We undertake no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available.

Contacts:MediaAmanda Sheldon, Head of Corporate Communicationsasheldon@arcutis.com

InvestorsEric McIntyre, Head of Investor Relationsemcintyre@arcutis.com

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Arcutis Submits Topical Roflumilast Cream New Drug Application to FDA for the Treatment of Adults and Adolescents with Plaque Psoriasis -...