From First Flare to Treatment-Free Intervals: Prescribing Nonsteroidal Topicals for Atopic Dermatitis

Atopic dermatitis has long occupied a contested space between specialties — a skin disease that is, at its core, a systemic inflammatory condition. For decades, that ambiguity meant the disease was largely managed reactively: topical corticosteroids for flares, referral to dermatology for anything more complicated, and a slow accumulation of cumulative steroid exposure that received far less clinical scrutiny than it deserved. That dynamic has changed fundamentally over the past 8 years. The approval of dupilumab in 2017 inaugurated a new era of precision immunotherapy for atopic dermatitis, establishing proof of concept that blocking the IL-4/IL-13 axis could produce durable disease control¹ — and triggering a cascade of drug development that has since generated multiple approved biologics (tralokinumab,² lebrikizumab³) and oral JAK inhibitors (abrocitinib,⁴ upadacitinib⁵) for moderate-to-severe disease. But as systemic options expanded, a parallel question emerged: for patients with limited or moderate disease who do not yet warrant a biologic, was the topical armamentarium keeping pace? The answer, increasingly, is yes — with 3 new non-steroidal topical agents approved in recent years representing genuinely differentiated mechanisms and meaningfully expanded options for the patients who might otherwise remain in a steroid-dependent cycle.

Against this backdrop, HCPLive convened a group of allergists and practitioners from the Philadelphia area for a clinical forum focused on ruxolitinib, tapinarof, and roflumilast — the 3 newest non-steroidal topical agents for atopic dermatitis. The discussion was moderated by Dareen Siri, MD, an allergist-immunologist at Midwest Allergy Sinus Asthma, and Assistant Professor, Southern Illinois School of Medicine. The group included specialists managing atopic dermatitis across a wide age range and disease spectrum, from private practice allergists in South Jersey to university-based providers at Penn Medicine. Before the clinical data was reviewed, the session opened with a broader reflection on a persistent challenge in allergy: despite allergists' expertise in managing the full atopic march — atopic dermatitis alongside asthma, food allergy, rhinitis, and EoE⁹ — the specialty remains largely invisible in industry educational programming for atopic dermatitis, with speaker panels dominated almost exclusively by dermatologists.

“I think the problem is that we're not talking to each other. I think that we all are capable of taking care of these patients. So if you look at the laws, we're licensed to practice medicine, so anyone can do what they want,” one panelist said.

The forum's timing was significant. Ruxolitinib had recently received expanded approval for pediatric patients as young as 2 years old⁷; tapinarof had completed open-label extension data demonstrating sustained treatment-free intervals after clearance⁸; and roflumilast cream had added seborrheic dermatitis and psoriasis to its label, positioning it as a multi-indication topical with a clean tolerability profile.¹⁰ Together, the 3 drugs represent a new paradigm in topical AD management — 1 centered not on short-course steroid suppression but on targeted anti-inflammatory pathways, skin barrier restoration, and the possibility of meaningful time off treatment.⁶ The panel's task was to make sense of where these agents fit in real clinical practice: how to explain the JAK box warning, when to escalate to a biologic, and how to navigate an insurance landscape where, as more than one panelist noted with some exasperation, it is often easier to obtain approval for a dupilumab injection than for a cream.

The panel reached clear practical consensus on several fronts. Topical JAK inhibition — specifically ruxolitinib — emerged as the preferred first-line non-steroidal option for most panelists if access and cost were not barriers, driven by its speed of action (demonstrable itch relief within 15 minutes), high IGA 0/1 response rates (~56% in pediatric trials at 8 weeks, even higher in adults), and treatment-free intervals exceeding four months after initial clearance in as-needed extension phases. The box warning, which originates from an oral surveillance study in older RA patients with cardiovascular risk factors — entirely distinct from the topical AD population — was discussed as a communication challenge rather than a clinical contraindication, with panelists sharing strategies that emphasize the topical-vs-systemic pharmacokinetic distinction, contextualize the warning relative to the well-documented but rarely discussed risks of chronic high-potency TCS use, and frame prescriber willingness to recommend the drug for family members. Tapinarof drew genuine scientific interest for its unique agonist mechanism — the only agent in the topical AD space that restores skin barrier proteins and activates the NRF2 antioxidant pathway rather than suppressing inflammation alone — but some panelists described real-world results that didn't consistently match trial data, attributing the gap to more complex patient populations, vehicle characteristics, and application technique. Roflumilast was positioned as the most conservative option: lower efficacy at the endpoint assessed, but no box warning, no contact dermatitis signal, no follicular events, and a clean fit for mild disease and maintenance, with the added clinical utility of dual indications for psoriasis and seborrheic dermatitis.

Perhaps the forum's most practically significant discussion concerned the structural barriers that prevent these agents from reaching the patients who need them. The panel was unanimous that biologic prior authorization is currently easier to obtain than coverage for any of the 3 topical agents — a perverse incentive that pushes appropriate topical candidates toward systemic therapy. Rep visits and sample availability in-office were identified as major drivers of prescribing behavior; without them, clinicians default to familiar habits and may not know how to navigate specialty pharmacy or coupon programs. Patient psychology was equally discussed: adolescent males, high-BSA patients, and those who present after years of treatment failure often arrive expecting injections rather than creams, and the "it's just another cream" dismissal from patients whose primary care providers haven't explained the mechanistic distinctions is a real and recurring obstacle. Panelists found treatment-free interval data — 120+ days for ruxolitinib, 74–80 for tapinarof — to be among the most persuasive patient counseling tools, offering a tangible answer to the question of whether topical therapy can provide durable, not just temporary, relief. The message that emerged was clear: the topical toolbox has genuinely advanced, but its clinical impact depends on closing the gap between what the trials show and what patients and prescribers actually know.

References:

1. Simpson EL, Bieber T, Guttman-Yassky E, et al; SOLO 1 and SOLO 2 Investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335-2348. doi:10.1056/NEJMoa1610020

2. Wollenberg A, Blauvelt A, Guttman-Yassky E, et al; ECZTRA 1 and ECZTRA 2 Investigators. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br J Dermatol. 2021;184(3):437-449. doi:10.1111/bjd.19574

3. Silverberg JI, Thyssen JP, Faerber M, et al. Phase 3 trial of lebrikizumab in moderate-to-severe atopic dermatitis (ADvocate1 and ADvocate2). N Engl J Med. 2023;388(12):1080-1091. doi:10.1056/NEJMoa2206714

4. Silverberg JI, Simpson EL, Thyssen JP, et al. Efficacy and safety of abrocitinib in patients with moderate-to-severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2021;157(8):896-903. doi:10.1001/jamadermatol.2021.2345

5. Guttman-Yassky E, Thaçi D, Pangan AL, et al. Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020;145(3):877-884. doi:10.1016/j.jaci.2019.11.025

6. Kim BS, Howell MD, Sun K, Papp K, Nasir A, Kuligowski ME; TRuE-AD1 and TRuE-AD2 Investigators. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J Allergy Clin Immunol. 2020;145(2):572-582. doi:10.1016/j.jaci.2019.08.031

7. US Food and Drug Administration. FDA approves ruxolitinib cream for atopic dermatitis in patients aged 2 years and older. Published September 2025. Accessed March 11, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ruxolitinib-atopic-dermatitis-pediatric-patients

8. Paller AS, Stein Gold L, Soung J, et al. Efficacy and patient-reported outcomes from a phase 2b, randomized clinical trial of tapinarof cream for the treatment of adolescents and adults with atopic dermatitis. J Am Acad Dermatol. 2021;84(3):611-619. doi:10.1016/j.jaad.2020.10.038

9. Eichenfield LF, Stripling S, Fung S, et al. Recent developments and advances in atopic dermatitis: a focus on epidemiology, pathophysiology, and treatment in the pediatric setting. Paediatr Drugs. 2022;24(4):293-305. doi:10.1007/s40272-022-00499-x

10. US Food and Drug Administration. FDA approves roflumilast cream for atopic dermatitis and expands indications to include seborrheic dermatitis and plaque psoriasis. Accessed March 11, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-roflumilast-cream