Allergists Debate: Which Nonsteroidal to Use for Atopic Dermatitis?

How Can Allergists Counsel Steroid Phobia?

Atopic dermatitis is among the most prevalent and burdensome inflammatory skin diseases in the United States, affecting an estimated 13% of children and 7% of adults, with disease burden driven primarily by itch, sleep disruption, and quality-of-life impairment that extends well beyond the skin to encompass behavioral effects in children, social withdrawal in adolescents, and occupational and cosmetic concerns in adults.1

The standard topical armamentarium — corticosteroids and calcineurin inhibitors — has remained largely unchanged since tacrolimus received FDA approval in 2000, and both drug classes carry limitations that generate persistent patient hesitancy: skin atrophy, dyspigmentation, and rebound for corticosteroids; burning, stinging, and a contested black box warning for calcineurin inhibitors.2 Since 2023, 3 mechanistically distinct non-steroidal topical agents have been added to the AD treatment landscape: tapinarof cream 1% (Vtama; Organon/Dermavant), an aryl hydrocarbon receptor agonist; ruxolitinib cream 1.5% (Opzelura; Pfizer/Incyte), a JAK1/JAK2 inhibitor; and roflumilast cream 0.15%/0.05% (Zoryve; Arcutis), a PDE4B inhibitor — all approved for patients 2 years of age and older, all indicated for mild-to-moderate AD, with tapinarof additionally indicated across all severity levels and for concurrent use with systemic biologics.3–5

ADORING 1 and 2, the pivotal phase 3 trials for tapinarof, enrolled 813 patients (80% pediatric), demonstrating vIGA treatment success rates of 45.4% and 46.4% versus 13.9% and 18.0% with vehicle at week 8 (P <.0001 for both), with approximately 55% achieving EASI-75 response and 32% reaching no-to-minimal itch by week 8.3 The ADORING 3 open-label extension found that 81.6% of 728 patients achieved clear or almost clear skin at least once over 48 weeks, and among those who achieved complete clearance, the mean first treatment-free interval was 79.8 consecutive days — a clinical data point without precedent in the topical AD landscape.6

Against this backdrop, HCPLive convened a group of allergist-immunologists from the Dallas–Fort Worth metropolitan area for an informal dinner roundtable on non-steroidal topical therapy in atopic dermatitis. The forum was moderated
Matthew Feldman, MD, board-certified allergist-immunologist at Preston Hollow Allergy in North Dallas with 12 years of faculty and clinical experience, and included colleagues from DFW-area allergy practices managing mixed pediatric and adult atopic dermatitis populations. The panel’s composition — spanning solo integrative medicine practices, suburban multi-site allergy groups, and practices anchored between major pediatric referral networks — captured a practically oriented perspective on how non-steroidal topicals are integrated, perceived, and navigated in the allergist’s office relative to the dermatology and pediatric primary care settings from which most patients arrive.

The forum’s most consistent theme was the allergist’s particular capacity for patient education and shared decision-making in atopic dermatitis — a capacity the panel attributed to longer appointment time, deeper familiarity with type 2 inflammatory biology, and the ability to contextualize atopic dermatitis within the atopic march that brings many of these patients to allergy clinics in the first place. Panelists described a consistent referral profile: parents seeking 1 root cause, often a food allergy, who arrive frustrated after dermatology or pediatric visits in which they received sample tubes and 2-minute explanations.

Social media, and TikTok in particular, was identified as a central barrier to first-line therapy: patients arrive with documented fear of topical corticosteroid withdrawal syndrome and a reflexive aversion to anything with a black box warning — including calcineurin inhibitors — that precedes any clinical conversation about benefit-risk. The structural consequence is that patients who are steroid-phobic are often equally JAK inhibitor–phobic when they see ruxolitinib’s box warning, while tapinarof’s absence of a box warning, BSA restriction, or biologic co-prescribing limitation makes it easier to introduce to patients already resistant to steroids. Insurance step-therapy mandates layer onto this: most payers require documented failure of a high-potency corticosteroid and a calcineurin inhibitor before approving a biologic, meaning clinicians often prescribe crisaborole or pimecrolimus not for anticipated clinical benefit but to generate an approvable prior authorization trail. Sleep disruption — estimated to affect 60–80% of children with moderate-to-severe atopic dermatitis — was endorsed by all panelists as the most persuasive patient-centric argument for escalating therapy, with 1 panelist describing the moment a parent hears that her child’s sleep could normalize as a visible weight lifting: “Is that possible? Like, yes. It is so possible.”

What Were Clinicians’ Clinical Experience?

When the moderator asked panelists to name their non-steroidal topical of first choice, tapinarof emerged as the clear preference — driven not primarily by its phase 3 efficacy data but by a combination of practical advantages that dermatology-facing trial publications undersell. No prior authorization requirement through the specialty pharmacy partner, a $35 cash-pay option for commercially uninsured patients, compatibility with concurrent biologic therapy, once-daily dosing, no BSA restriction, and the ability to apply it anywhere on the body including the face and periorbital region without the steroid-avoidance counseling required for corticosteroids. Panelists described essentially no patient-reported stinging — including in actively inflamed lesions — with the ability to apply a sample tube in-office during the visit as a real-time tolerability demonstration. The follicular event rate of approximately 12% in ADORING 3 was not encountered in practice by any panelist who had used the drug.6

The tapinarof origin story — derived from a compound found in nematode bacteria — was cited by multiple panelists as a surprisingly effective patient communication tool. Several panelists described using tapinarof successfully as a biologic-deferral strategy, enrolling patients for a 4-to-6-week trial before initiating a biologic that had already been approved, in some cases avoiding the biologic entirely.

As 1 panelist described the result in a 4-year-old: “She was very relieved and very happy. Her skin felt so smooth. And that was just really heartwarming to see that because a lot of these patients have been struggling so much. They can’t find a topical that first of all, they can tolerate, let alone that can actually help with inflammation. So the mom was in tears.”

Ruxolitinib was described as a niche agent for localized disease — particularly hand and eyelid dermatitis — where its rapid itch relief (documented as a mean 4-point improvement in peak pruritus NRS within 4 hours in TRuE-AD) is clinically relevant and the 20% BSA restriction is not a limiting factor.4 Roflumilast drew the least enthusiasm, with 1 panelist describing more stinging than tapinarof — though less than crisaborole — and coverage described as harder to achieve than for the other 2 agents. The panel’s consensus unmet need was not better evidence but better infrastructure: more samples reaching allergists with the same frequency they reach dermatology, clearer step-therapy language from insurers, and an age indication extending below 2 years where, as panelists noted, the most impactful window for interrupting the atopic march may actually lie.

References

1. Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study. J Allergy Clin Immunol. 2013;132(5):1132–1138. doi:10.1016/j.jaci.2013.08.031

2. AAAAI/ACAAI JTF Atopic Dermatitis Guideline Panel; Chu DK, Schneider L, Asiniwasis RN, et al. Atopic dermatitis (eczema) guidelines: 2023 AAAAI/ACAAI Joint Task Force on Practice Parameters. Ann Allergy Asthma Immunol. 2024;132(3):274–312. doi:10.1016/j.anai.2023.11.009

3. Silverberg JI, Eichenfield LF, Hebert AA, et al. Tapinarof cream 1% once daily: significant efficacy in the treatment of moderate to severe atopic dermatitis in adults and children down to 2 years of age in the pivotal phase 3 ADORING trials. J Am Acad Dermatol. 2024;91(3):457–465. doi:10.1016/j.jaad.2024.05.023

4. Papp K, Bhalla B, Torres T, et al; TRuE-AD Investigators. Ruxolitinib cream 1.5% for atopic dermatitis in adolescents and adults (TRuE-AD1 and TRuE-AD2): two phase 3, randomised, double-blind, vehicle-controlled trials. Lancet. 2021;397(10290):2160–2173. doi:10.1016/S0140-6736(21)00586-1

5. Davis DMR, Chovatiya R, Silverberg JI, et al. Roflumilast cream for the management of atopic dermatitis in adults and children: pooled analysis of INTEGUMENT-1 and INTEGUMENT-2. J Am Acad Dermatol. 2024. doi:10.1016/j.jaad.2024.02.038 [confirm DOI upon indexing]

6. Bissonnette R, Stein Gold L, Kircik L, et al. Skin clearance, duration of treatment-free interval, and safety of tapinarof cream 1% once daily: results from ADORING 3, a 48-week phase 3 open-label extension trial in adults and children down to 2 years of age with atopic dermatitis. J Am Acad Dermatol. 2025;93(3):707–714. doi:10.1016/j.jaad.2025.05.1391