Eric Simpson, MD

Credit: OHSU

The majority of individuals with atopic dermatitis (AD) who do not attain the Investigator's Global Assessment treatment success (IGA-TS) at 8 weeks can see substantial improvement when treated with ruxolitinib cream by the end of 52 weeks, according to new findings.1

These findings were the result of a post-hoc analysis on both adolescents and adults that have AD who were not able to achieve IGA-TS at 8 weeks. The investigators noted that several post-hoc assessments of trials on systemic AD treatments showed that regulatory drug approvals’ typical definition of success as clear or almost clear skin (IGA) may not be adequate to capture all relevant improvements.²

Given the research team’s awareness that AD patients could potentially benefit from treatment past 8 weeks, they conducted this new analysis. This research was led by Eric L. Simpson, MD, from Oregon Health & Science University in Portland, Oregon.

“The objective of this post hoc analysis was to investigate the short- and long-term efficacy, safety, and disease control of ruxolitinib cream in adolescents and adults with AD who did not achieve IGA-TS at week 8, using pooled data from two phase 3 studies,” Simpson and colleagues wrote.

Background and Findings

The investigators’ analysis looked at pooled data from two phase 3 trials, which were TRuE-AD1 and TRuE-AD2. These studies involved identical designs, including eligible participants aged ≥12 years with a minimum of 2 years of AD history, IGA scores of 2 or of 3, and 3% - 20% affected body surface area (BSA).

The team’s criteria for participant exclusion were immunocompromised status, unstable disease course, different types of other skin conditions, and utilization of AD therapies besides emollients at the time of the study. The study’s subjects were randomly assigned to either of 2 potential ruxolitinib cream regimens or the vehicle cream for an 8-week course (VC period) with subsequent 44-week ruxolitinib treatment for certain of them.

The investigators’ response examination mainly looked at n those not achieving IGA-TS by the 8-week mark. Several different types of endpoints like Itch Numerical Rating Scale (itch NRS2) reduction, Eczema Area and Severity Index (EASI-50), Dermatology Life Quality Index (DLQI) improvement, changes in Children’s DLQI (CDLQI), and IGA reduction were utilized by the team.
The research team’s composite endpoint was used to determine meaningful results occurring from the VC period. Subjects’ longer-term responses during the LTS period were then looked at by the team for subjects initially randomized to ruxolitinib treatment who were not able to report IGA-TS at 8 weeks. Safety was also assessed across the 52-week study.

The 2 trials involved a total of 1249 subjects, with a randomization ratio of 2:2:1 being employed by the investigators. Those in the study were given the instruction to apply either the 0.75% ruxolitinib cream, the 1.5% ruxolitinib cream, or a vehicle cream twice-per-day for a duration of 8 total weeks before the later phase.

The investigators found that among those who were not able to reach IGA treatment success by the close of 8 week period–584 individuals in total—a notably higher proportion of these subjects who used either strength of ruxolitinib cream as opposed to the vehicle cream were able to reach each of the response criteria by the finish of 8 weeks.

The team noted that at least 1 of the responses to the endpoints was witnessed in a much greater amount of those who applied the cream, with percentages of 93.4% for the 0.75% strength and 90.9% for the 1.5% strength, compared to 69.0% for the vehicle cream (P < 0.0001 for both).

The investigators noted that, over the course of time, they reported progressive improvements in subjects’ control of their disease, with a substantial portion of them reaching IGA treatment success by the finish of week 52.

“Taken together, these results demonstrate that the vast majority of patients have a clinically meaningful response to ruxolitinib cream, and continued therapy beyond 8 weeks can result in additional benefit for patients with mild to moderate AD,” they wrote.

References

1. ^{Simpson, EL, Kircik, L, Blauvelt, A, Kallender, H, Kuo, Y, Ren, H, et al. Clinically relevant improvements in adults and adolescents with atopic dermatitis who did not achieve Investigator's Global Assessment treatment success following 8 weeks of ruxolitinib cream monotherapy. J Dermatol. 2023; 00: 1–8. https://doi.org/10.1111/1346-8138.16975.}
2. ^{Silverberg JI, Simpson EL, Ardeleanu M, Thaci D, Barbarot S, Bagel J, et al. Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator's Global Assessment: a pooled analysis of data from two phase III trials. Br J Dermatol. 2019; 181: 80–87.}
3. ^{Blauvelt A, Boguniewicz M, Brunner PM, Luna PC, Biswas P, DiBonaventura M, et al. Abrocitinib monotherapy in Investigator's Global Assessment nonresponders: improvement in signs and symptoms of atopic dermatitis and quality of life. J Dermatolog Treat. 2022; 33: 2605–2613.}