Enhancing Atopic Dermatitis Treatment: Insights From Cutting-Edge Studies and Clinical Perspectives Part 1

“We need to go beyond what we’ve had in the past,” Linda Stein Gold, MD, director of dermatology clinical research at Henry Ford Health in Detroit, Michigan, said, setting the tone for a recent Dermatology Times® Frontline Forum video series Beyond Steroids: Topical Dermatological Efficacy and Patient-Centric Perspectives. Stein Gold moderated a discussion exploring the unmet needs in nonsteroidal topical treatment for atopic dermatitis (AD), safety and efficacy data from the SCRATCH-AD (NCT04839380) and TRuE-AD3 (NCT04921969) studies, and approaches to discussing black box warnings with patients. According to results from a patient survey published recently, a majority of patients ranked the reduction of itch and the improvement of skin dryness and cracking as top priorities (Figure 1).¹

Guidelines and Recommendations

Stein Gold emphasized the significance of evidence-based guidelines updated by the American Academy of Dermatology (AAD) in the past year, stating, “Guidelines provide a road map for delivering high-quality care based on the best available evidence.” Brad Glick, DO, MPH, of the Glick Skin Institute in Margate and Wellington, Florida, echoed this sentiment and said, “Guidelines help health care providers make informed decisions about patient care and treatment strategies.” The panel discussed the significance of considering barrier restoration, corticosteroids, topical calcineurin inhibitors, PDE4 inhibitors, and Janus kinase (JAK) inhibitors into the treatment armamentarium.

The AAD updated its guidelines for the first time since 2014 with recommendations for AD management in patients who do not respond to topical therapies. After their comprehensive review, the academy recommended the use of dupilumab (Dupixent), tralokinumab (Adbry), baricitinib (Olumiant), abrocitinib (Cibinqo), and upadacitinib (Rinvoq); conditionally recommended phototherapy, cyclosporine, methotrexate, azathioprine, and mycophenolate; and did not recommend systemic corticosteroids.²

The experts highlighted the importance of evidence-based recommendations in guiding clinical practice, with Stein Gold noting, “These were given the strongest level of recommendation.” Before delving into the latest clinical trial data, the panel debriefed on therapies recommended to patients in their daily routines, including bathing followed by moisturization, wet wrap therapy with bandages, and basic skin care, before adding other therapies to the mix. Findings from recent studies have brought ruxolitinib (Opzelura) to the treatment landscape.

Recent Studies to Note

The panelists discussed the SCRATCH-AD study in relation to symptom resolution and patient outcomes. The study focused on the efficacy and safety of ruxolitinib cream, a topical JAK1/2 inhibitor. In findings from pivotal phase 3 trials, ruxolitinib cream 1.5% showed significant improvement in itch compared with a vehicle cream, starting as early as 12 hours after the initial application. A phase 2 open-label study aimed to understand the short-term clinical benefits of ruxolitinib cream. Participants applied the cream twice daily for 28 days. The primary end point was the change from baseline in peak pruritus numerical rating scale (PP-NRS) score at day 2. Secondary end points included changes in modified PP-NRS (mPP-NRS) score, Investigator’s Global Assessment (IGA) score, and safety measures. Results showed a mean change from baseline in PP-NRS score of –3.4 on day 2 and continued improvement through day 29. Changes from baseline in mPP-NRS score peaked at –4.2 at 4 hours post treatment. IGA scores improved over time, with mean changes of –1.4 on day 8, –2 on day 15, and –2.2 on day 29. Treatment-emergent adverse events (AEs) were reported in 30.6% of participants, with only 1 AE being related to treatment (grade 1 application site reaction). Skin treated with ruxolitinib cream showed a significant decrease in transepidermal water loss, reaching levels similar tononlesional skin by day 29. Rapid and sustained improvement in itch was observed as early as 15 minutes post application, with peak reduction at 4 hours. Overall SCRATCH-AD findings showed ruxolitinib cream 1.5% demonstrated rapid, substantial, and sustained improvement in itch and disease severity in patients with AD, supporting its efficacy and tolerability as a topical treatment for AD (Figure 2).³

Michael Cameron, MD, dermatologist at Cameron Dermatology in New York, New York, highlighted the importance of itch relief in improving quality of life for patients with AD, stating, “Some of the oral JAK inhibitors have put forth a lot of good data [showing] profound itch relief.” Glick raised a critical question about assessing remission in patients with AD, emphasizing the need to consider both itch and skin appearance in determining treatment success. He asked, “How are we going to assess remission in patients with atopic dermatitis? Is it going to be solely on itch? Is it in the appearance of the skin?” The panelists acknowledged the challenge of addressing the occasions where patients may experience persistent itching even after the rash has cleared. Lisa Swanson, MD, pediatric dermatologist at Ada West Dermatology and St Luke’s Children’s Hospital in Boise, Idaho, shared her observation regarding pediatric patients, noting that some may remain stuck in the itch-scratch cycle even after the rash has resolved, indicating the complexity of managing symptoms beyond visible skin manifestations.

The panelists also discussed the TRuE-AD3 study, which examined ruxolitinib’s efficacy, safety, and pharmacokinetics in pediatric patients. Swanson mentioned that the study included patients aged 2 to 11 years and highlighted the exciting findings, stating, “Spoiler alert: It’s exciting.” Stein Gold appreciated the study design, noting the structure of the trial where patients were treated for 8 weeks and then followed as needed for long-term safety up to week 52, similar to adult studies.

A significantly higher number of patients using ruxolitinib cream, regardless of strength, experienced at least a 2-point reduction in itch within approximately 12 hours compared with those using the vehicle cream (16.3% and 13.1% for ruxolitinib vs 6.9% for vehicle; both P < .05). This improvement continued through week 8, with rates of 58.3% and 65.1% for ruxolitinib compared with 29.4% for vehicle (both P < .0001). For a more substantial reduction of at least 4 points in itch (NRS4), significantly more patients using 0.75% and 1.5% ruxolitinib cream achieved this by day 2 compared with the vehicle group (8.9% and 11.2% for ruxolitinib vs 2.1% for vehicle; P < .005). By week 8, the rates increased to 41.5% and 51.5% for ruxolitinib and 15.8% for vehicle (P < .0001). The median time for patients using 0.75% and 1.5% ruxolitinib cream to achieve an NRS4 reduction from baseline was 15 and 13 days, whereas the vehicle group did not reach this end point (Figure 3).⁴

Swanson further elaborated on the baseline characteristics of the study participants, emphasizing the inclusion of patients from different age groups, which was beneficial for patients with skin of color. The panelists expressed enthusiasm about the study results and the potential of ruxolitinib in pediatric patients based on the TRuE-AD3 study findings.

When comparing the efficacy of ruxolitinib vs triamcinolone, the panelists provided insights based on the study findings. James Del Rosso, DO, dermatologist and investigator at the Del Rosso Dermatology Research Center in Las Vegas, Nevada, highlighted the superior efficacy of ruxolitinib, stating: “The ruxolitinib did substantially better in terms of EASI [Eczema Area and Severity Index] score reduction compared with triamcinolone.” Swanson supported this by mentioning, “The data at week 2 indicated that ruxolitinib was outperforming triamcinolone.” The panelists emphasized the faster onset of action of ruxolitinib, with Del Rosso noting comparisons to traditional topical steroids. They also discussed the significant reduction of itch with ruxolitinib compared with triamcinolone.

References

1. Silverberg JI, Mohawk JA, Cirulli J, et al. Burden of disease and unmet needs in atopic dermatitis: results from a patient survey. Dermatitis. 2023;34(2):135-144. doi:10.1089/derm.2022.29015.jsi
2. Davis DMR, Drucker AM, Alikhan A, et al. Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies. J Am Acad Dermatol. 2024;90(2):e43-e56. doi:10.1016/j.jaad.2023.08.102
3. Bissonnette R, Ren H, Nawaz H, Halden P, Saint-Cyr Proulx E. Three hundred ninety-six rapid, substantial and sustained reduction of itch in adults with atopic dermatitis applying ruxolitinib cream 1.5% (SCRATCH-AD). Br J Dermatol. 2023;188(suppl 3):ljad162.021. doi:10.1093/bjd/ljad162.021
4. Blauvelt A, Kircik L, Papp KA, et al. Rapid pruritus reduction with ruxolitinib cream treatment in patients with atopic dermatitis. J Eur Acad Dermatol Venereol. 2023;37(1):137-146. doi:10.1111/jdv.18571

Continued in part 2.