NEW YORK, NY -- For immediate control of a hand eczema flare, the old soak and smear approach with moisturizers or corticosteroids might live on, but they are moving to the back of the shelf for chronic mild-to-moderate disease.
Referring to the gamut of non-targeted therapies, including topical steroids, calcineurin inhibitors, and immunomodulators that have been used for decades, Alexandra Golant, MD, assistant clinical professor, department of dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, suggested that an era is ending.
"Largely, even fortunately, these have been replaced by our more targeted therapies," Golant said.
Just the day before updating options for hand eczema at the 27th Annual Winter Symposium -- Advances in Medical and Surgical Dermatology (MSWS) 2024, topical tapinarof, 1%, cream, a nonsteroidal anti-inflammatory, received US Food and Drug Administration (FDA) approval for atopic dermatitis (AD) for patients ages 2 and older. It was approved previously for psoriasis.
The introduction of yet another targeted topical anti-inflammatory meant that Golant's slides had to be updated. Along with 1.5% ruxolitinib cream (Opzelura) and 0.15% roflumilast cream (Zoryve), there are now three nonsteroidal topicals, although the extent of the evidence for efficacy with these drugs, especially for hand eczema, varies.
The mechanisms vary too. Tapinarof (Vtama) binds to and activates the aryl hydrocarbon receptor thereby inhibiting release of interleukin (IL)-17 and other cytokines. Ruxolitinib cream, which also has an indication for vitiligo, inhibits the JAK1 and JAK2 signaling pathways. Roflumilast cream, previously approved for plaque psoriasis, is a selective inhibitor of phosphodiesterase-4 (PDE4). By increasing intracellular cAMP, PDE4 inhibition indirectly prevents release of multiple inflammatory mediators.
While all three are considered nonsteroidal targeted topical anti-inflammatories and have provided a high degree of activity with a low risk of adverse events in pivotal double-blind AD trials, only ruxolitinib 1.5% cream has been tested in a large, controlled trial specifically in hand eczema, according to Golant.
In this multicenter double blind trial presented at the 2024 Fall Clinical Dermatology Conference, treatment success defined as an Investigator's Global Assessment-Chronic Hand Eczema score of 0 (clear) or 1 (almost clear) was 5-fold higher (53.2% vs 10.9%; P < .001) among those randomized to ruxolitinib cream relative to vehicle at 16 weeks.
"By day 7, patients on ruxolitinib were half way to the response seen at week 16," according to Golant, emphasizing that this drug works very quickly.
Itch was already improving by day 2. In addition, the Hand Eczema Severity Index score corresponding to 75% and 90% clearance was achieved by 80% and 64% of ruxolitinib-treated patients, respectively, at 16 weeks. Both were several times higher than scores in the vehicle arm.
Multicenter trials with roflumilast and tapinarof creams have not been conducted specifically for hand eczema, but Golant cited case reports with roflumilast that also provides very high rates of response consistent with efficacy seen for AD overall.
Based on the activity already shown in AD overall, "I am sure we will see similar efficacy [for hand eczema] with our newest agent, tapinarof," she added.
If these were not enough to retire steroids and less targeted therapies for chronic hand eczema, others are likely coming, Golant reported. In particular, she cited ongoing phase 3 trials with the topical pan-JAK inhibitor delgocitinib for chronic hand eczema. The FDA accepted the new drug application for delgocitinib for the treatment of hand eczema several months ago. If approved, delgocitinib will become the first and only treatment with this indication.
These topical agents are effective for mild-to-moderate hand eczema, but Golant also emphasized that the threshold for moving to systemic therapies for more severe disease is being lowered. Specifically, she said that even patients with isolated hand and foot eczema are reasonable candidates for systemic therapies independent of body surface area when involvement is severe.
"It is thought that about one third of patients of patients who suffer [from hand eczema] have moderate to severe disease," and this level of severity has "can very significantly limit quality of life," said Golant, noting that disease imposes an enormous psychological burden, often limits ability to work, and can impair social activities.
Of monoclonal antibodies, Golant listed the IL-13 inhibitors tralokinumab (Adbry) and lebrikizumab. Lebrikizumab (Ebglyss) was approved in September of 2024 for patients with AD, ages 12 years and older.
Of the oral JAK inhibitors, both upadacitinib and abrocitinib have indications for AD, noted Golant, who said that the evidence of efficacy specifically for hand eczema varies. However, she considers both reasonable options for those who are not achieving adequate control with topical agents. The experimental JAK inhibitor gusacitinib has already been evaluated for hand eczema in a phase 2 trial.
There have been no major comparative trials for treatment options in hand eczema whether those for mild-to-moderate or moderate-to-severe disease. As a result, there is no objective approach to selecting a first- or second-line therapy among the available options, but the important point is that targeted therapy is increasingly moving nontargeted agents to the back of the line, according to Golant.
She did not suggest that the older agents no longer have a role. There are circumstances in which these agents might help. For example, Golant said she still considers soak and smear a reasonable adjunct for hand eczema flares. Yet for chronic hand eczema, she considers the data overwhelmingly in favor of newer treatments with better efficacy and, for the most part, better safety.
Recognizing that there is limited evidence to select among the most effective therapies in mild-to-moderate hand eczema, Adam Friedman, MD, professor and chair of dermatology, George Washington University, Washington, DC, called for "personalization of the management strategy and incorporation of patient preferences for better adherence."
However, he also acknowledged formulary approved options as a factor.
"Access will be the most important determinant when picking a potion, as the most effective medication is often the one the patient can actually pick up," he said when asked how he might prioritize the growing availability of choices. Friedman was not at the meeting but was asked to comment.
Golant reported financial relationships with AbbVie, Amgen, Arcutis, Bristol-Myers Squibb, Dermavant, Galderma, Incyte, Janssen, Leo Pharma, Lilly, Pfizer, Regeneron, and Sanofi. Friedman reported no potential conflicts of interest.