Symposium Highlights New Research on JAK, PDE-4 Inhibitors

New insights into the treatment of atopic dermatitis (AD) provided the majority of clinical insights presented on April 30 at Revolutionizing Atopic Dermatitis 2023. Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego and professor of dermatology and pediatrics and vice-chair of the department of dermatology at UC San Diego School of Medicine, and Jonathan Silverberg, MD, PhD, MPH, associate professor of dermatology and director of clinical research and contact dermatitis at The George Washington University School of Medicine and Health Sciences in Washington, DC. They presented on topical therapies and oral Janus kinase (JAK) inhibitors, respectively.

Eichenfeld discussed new innovations in nonsteroid topical therapies, especially in pediatric patients. Topical ruxolitinib 1.5% cream is one topical JAK inhibitor that has been approved for patients 12 years and older for AD, being used for short-term and noncontinuous chronic treatment of mild to moderate AD.

Ruxolitinib was found to have anti-inflammatory and antipruritic effects with superior efficacy compared with a vehicle in an 8-week double-blind, vehicle-controlled trial; 53.8% of patients had clear/almost clear results compared with 15.1% in the vehicle group. Itch reductions were also found within 12 hours of first application of the ruxolitinib 1.5%. A sub-analysis in adolescents was also conducted and achieved similar results.

Eichenfield also presented the results of a 1-year extension study that found that topical ruxolitinib was generally safe to use.

“I really want to highlight the adverse event profile, because it was really quite low,” he said. “…I think it’s important for us to know as clinicians about how the drug appears to be fairly safe in clinical practice when used the right way.”

The right way, according to the study, would be as needed for longer term disease, with the ruxolitinib cream showing effective disease control and tolerability in a 44-week safety period. A separate study evaluating the safety of ruxolitinib cream in adolescents and children found no clinically meaningful changes in mean chemistry or hematology values and no consistent change in bone biomarkers.

Inphosphodiesterase-4 inhibitors, Eichenfield highlighted roflumilast as a novel inhibitor that has been approved for psoriasis treatment in the past.

“In the younger age groups, we now have the core data of the phase 3 clinical trials in patients aged 6 and older,” he said. “Be aware that for roflumilast, we have different concentrations for different diseases and potentially for different ages as well as for different conditions.”

The Integument-1 and -2 phase 3 trial results were highlighted; the pair of trials tested roflumilast 0.15% cream applied daily for patients with mild to moderate AD.

"The survey results show that the clear/almost clear was about 30% to 32% vs 12% and 15% in the vehicle group,” said Eichenfield. “And an adverse event profile was…unremarkable. You see a little bit of headache, but you also see some of that in the vehicle as well.”

A last study evaluating the efficacy of tapinarof 1% cream for children aged 2 years and older was presented as well. The results of the ADORING 2 trial found there was a 46.4% clear/almost clear rate compared with the vehicle that had 18.0% after 8 weeks. Adverse events were mild to moderate.

Eichenfield concluded that topical therapies were crucial in the care of AD in the patients’ lifetime. Understanding and therapy of AD continues to evolve through various research on the subject and its treatments.

Silverberg closed the panel by speaking about new insights in oral JAK inhibitors in the treatment of AD, primarily focusing on the efficacy of abrocitinib, baricitinib, and upadacitinib, which have recently been approved to treat AD.

Silverberg presented the results of the JADE study, which tested the effectiveness of abrocitinib to 96 weeks. “These are looked at as observed data, but what you’re seeing is very, very flat curves for pinch responses,” he said. “What we see is maybe the 1- or 2-mg doses climbing in efficacy even more over time but really very flat, durable curves.”

He also presented results from the small JADE-DARE study about the efficacy of abrocitinib 200 mg after an inadequate response to dupilumab, which found that 72% had some improvement from their baseline but were classified as nonresponders overall when using dupilumab. However, 91% had improved Eczema Area and Severity Index (EASI) after 12 weeks of using abrocitinib 200 mg, with EASI scores below 16. Switching from dupilumab to upadacitinib also was associated with an increase in efficacy.

The efficacy of abrocitinib vs dupilumab in patients with AD with or without asthma was also tested in the JADE-COMPARE trial, which was held over 16 weeks in adults with moderate to severe AD.

“What was found was that those with asthma have consistently more adverse events in general compared to those who didn’t. But when you actually look at the efficacy for either drug, whether they have asthma or didn’t have asthma, what we can potentially say is there’s really no difference whether they do or don’t have asthma,” said Silverberg.

Real world data from case series reports from Israel and Italy were presented where no severe AEs were reported, corroborating the safety of the treatment.

Another area where oral JAK inhibitors were found to be effective were hand eczema when paired with topical corticosteroids, which was tested in the JADE-DARE trial. When the oral JAK inhibitor, baricitinib, was used for younger children with moderate to severe AD, improvements in multiple severity measures were seen by the end of the trial, in week 16, and as early as week 4 with unremarkable adverse event profiles. All children received 3 doses of baricitinib stratified by age: 2 to 9 years and 10 to 17 years. Children aged 2 through 9 received 0.5, 1.0, and 2.0 mg whereas those aged 10 through 17 received 1.0, 2.0, and 4 mg.

Silverberg concluded that oral JAK inhibitors were found to be effective in different subsets of patients with moderate to severe AD.

“There’s good real-world long-term efficacy, safety, a lot of promise, and versatility for these and we’ll learn a lot more about where they’re potentially going to be used,” Silverberg concluded.