Category: Skin Conditions

Researchers Develop Online Tool to Calculate Psoriatic Arthritis Risk

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In research published in Arthritis & Rheumatology, investigators developed and validated a tool called PRESTO that identifies patients with psoriasis who face an elevated risk for developing psoriatic arthritis and may therefore benefit from preventive therapies. The PRESTO calculator is available online.

The University of Toronto psoriasis cohort followed 635 patients with psoriasis, and 51 and 71 developed psoriatic arthritis during 1-year and 5-year follow-up periods, respectively. The risk of developing psoriatic arthritis within 1 year was higher in patients with younger age; male sex; family history of psoriasis; back stiffness; nail pitting (dents, ridges, and holes in the nails); joint stiffness; use of biologic medications; poor health; and pain severity. The risk of developing psoriatic arthritis within 5 years was higher in patients with morning stiffness, psoriatic nail lesion, psoriasis severity, fatigue, pain, and use of systemic non-biologic medication or phototherapy.

Taking these data into account, PRESTO uses a mathematical model to estimate a patient’s risk of developing psoriatic arthritis.

“The PRESTO tool could serve future efforts to reduce the progression from psoriasis to psoriatic arthritis. For example, PRESTO can be used to enrich prevention trials with at-risk populations. It can also identify patients with psoriasis who can benefit from early treatments, and it can serve as an educational tool for patients to increase awareness of psoriatic arthritis risk,” said corresponding author Lihi Eder, MD, PhD, of Women’s College Hospital and the University of Toronto, in Canada. “Ultimately, we hope that these efforts will improve the lives of people living with psoriatic disease.”

Source: Wiley

New Oral Psoriasis Drug a Step Closer After Successful Clinical Trials

Source: Danilo Alvesd on Unsplash

In a Phase 2b clinical trial, patients who took the peptide-based drug candidate JNJ-2113 had a 75% improvement in their plaque psoriasis compared to placebo, passing an important milestone in developing an oral treatment for the common skin disease. The drug is being developed by a company launched from The University of Queensland’s Institute for Molecular Bioscience (IMB) in collaboration with Janssen.

Protagonist Therapeutics was spun out of work by Associate Professor Mark Smythe to develop new drugs for conditions previously only treated with injectables. Dr Smythe said the trial result was a significant achievement for patients and the scientists involved.

“The trial has shown it’s possible to treat systemic diseases like psoriasis with peptide-based drugs that are orally delivered,” Dr Smythe said.

“Diseases such as psoriasis and inflammatory bowel disease have targets that previously could only be blocked by large molecules called macromolecular antibodies, which had to be injected because they’re too big to be taken in pills.

“The key to finding a molecule that worked but was small enough to be taken orally was seeing the animal venom research of my IMB colleagues.

“I realised that the constrained peptide molecules in venoms could both block the right targets and were small.”

Dr Smythe and his team developed techniques to stabilise the peptides enough so that they could be developed into an oral drug.

Protagonist was founded in 2001 with commercial support from UniQuest Pty Ltd, UQ’s commercialisation company.

Protagonist is based in the USA with an office in Brisbane and is one of 15 spin-out companies from IMB and one of 125 start-ups based on UQ intellectual property.

Source: The University of Queensland

No One Type of Emollient is Best for Children with AD

Atopic dermatitis
Source: Wikimedia CC0

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!

New JAK1 Inhibitor Abrocitinib Effective in Atopic Dermatitis

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.