New therapies, expanding uses for existing therapies, and links between atopic dermatitis (AD) and multiple inflammatory conditions have made headlines so far this year.
IL-13 Inhibitor Impresses in Phase III Trials
Favorable results from three phase III clinical trials in atopic dermatitis provided momentum for an anticipated FDA decision on lebrikizumab -- which has been put off for a while longer.
The phase III ADhere trial, the most recent of the three studies, showed that twice as many patients met the primary endpoint of Investigator's Global Assessment (IGA) score of 0 or 1 (clear or nearly clear) at week 16 as compared with placebo injections (41.2% vs 22.1%). Additionally, 70% of lebrikizumab-treated patients had at least 75% improvement in the Eczema Area and Severity Index (EASI) versus 42% of the placebo group. The results added to those of two trials with favorable outcomes reported in 2022.
ADhere involved 211 adults and adolescents with moderate to severe AD, randomized 2:1 to lebrikizumab or placebo, in addition to corticosteroids. If approved, lebrikizumab would join an ever-lengthening list of new drugs that target AD through various pathways of inflammation.
"Due to the heterogeneity of AD, there remains a need to provide additional therapeutic options for long-term management," wrote Eric Simpson, MD, of Oregon Heath & Science University in Portland, and ADhere coinvestigators in JAMA Dermatology.
With the volume of favorable outcomes with the interleukin (IL)-13 inhibitor, lebrikizumab appeared poised for FDA approval. However, the agency on the approval process with a list of problems at a third-party manufacturing facility -- not the drug itself -- that require attention before approval can be reconsidered.
According to a statement from drug sponsor Eli Lilly, the company "will continue to work closely with the third-party manufacturer and the FDA to address the feedback in order to make lebrikizumab available to patients."
Topical PDE4 Inhibitor Get High Marks
Topical roflumilast led to ≥75% improvement in the EASI score within 4 weeks in more than 40% of patients with moderate or severe AD, including complete clearance in about 30% of patients in two phase III, randomized, vehicle-controlled trials. A similar proportion of patients in the two trials also had rapid and clinically meaningful improvement in itch.
"We observed significant improvement based on EASI-75 as early as 1 week after treatment initiation," Simpson said during a presentation at the American Academy of Dermatology meeting. "A reduction in pruritus was observed at 24 hours following the first application. No adverse event occurred in more than 3.5% of patients, with low rates of application-site pain in both the roflumilast- and vehicle-treated patients."
A 0.3% formulation of roflumilast (Zoryve) was approved in 2022 for plaque psoriasis, and various concentrations are being evaluated in clinical trials of psoriasis, seborrheic dermatitis, and AD. Simpson reported findings from two trials involving a total of 1,337 patients randomized 2:1 to 0.15% roflumilast or vehicle control.
The primary endpoint was IGA of 0 or 1 after 4 weeks, plus at least a 2-point improvement from baseline. Statistically significant differences in favor of the PDE4 inhibitor emerged within 1 to 2 weeks (P<0.0001). About twice as many patients in the roflumilast groups met the primary endpoint as compared with the control groups. All secondary endpoints showed a significant difference in favor of the active treatment.
Dupilumab Effective in Seborrheic AD
Patients with seborrheic AD had statistically significant and clinically meaningful improvement in body surface area (BSA), disease severity, and pruritus after 16 weeks of treatment with dupilumab (Dupixent), according to a post hoc analysis of six randomized trials.
Totaling 209 patients across the studies, the analysis showed that BSA involvement decreased by 40-63%, EASI by 59-79%, and pruritus by 34-56%. Serum levels of inflammatory biomarkers declined in concert with symptoms, reported Amy Paller, MD, of Northwestern University Feinberg School of Medicine in Chicago, and coauthors in JAMA Dermatology.
"Erythrodermic AD is a serious manifestation of AD that can lead to health-threatening complications," the authors noted. "In the analyzed trials, patients with erythrodermic AD had higher baseline disease severity ... and reported worse quality of life at baseline compared with the overall populations."
"Overall, dupilumab was well tolerated, with most adverse events being mild or moderate in severity, and with no imbalance in [treatment-emergent adverse events] and treatment-emergent serious adverse events between dupilumab and placebo groups," they added.
The subgroup analysis provided much-needed data on clinical management of erythrodermic AD, according to the author of an accompanying editorial.
"Erythrodermic AD is a severe clinical presentation of AD with high morbidity and mortality, which can be challenging to manage," wrote Dawn Eichenfield, MD, PhD, of the University of California San Diego. "The implementation of dupilumab and other advanced systemic therapies in AD will provide new tools for management of erythrodermic AD."
AD: It's Not Just a Skin Disease
The systemic nature of AD emerged in multiple reports linking it to other conditions, with inflammation the apparent common thread, with one notable exception. So far this year, 鶹ý has reported associations between AD and:
The studies added to evidence of associations between AD and cardiovascular disease, metabolic syndrome, diabetes, vasculitis, kidney disease, and other conditions.
Other AD news this year included:
Meta-Analysis Points to Most Effective Topical Treatments for Atopic Dermatitis
'Enhanced' Eczema Treatment Cut Food Allergy Risk, but at What Cost?
Peanut-Allergic Kids With Other Food Allergies, Eczema See Responses With EPIT
Childhood Eczema Rose in Past Two Decades, With Unexplained Racial Divides
Guidance for Managing Atopic Dermatitis in Patients of Color
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