Ruxolitinib Cream Shows Long-Term Safety in AD, Potential for PN Treatment

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Data presented at the 2025 American Academy of Dermatology (AAD) Annual Meeting in Orlando, Florida, reiterated ruxolitnib cream (Opzelura; Incyte) as a safe, effective treatment for atopic dermatitis (AD) and highlighted its potential to treat adults with prurigo nodularis (PN).

Two posters presented at the 2025 American Academy of Dermatology Annual Meeting reaffirmed the impact of ruxolitinib cream (Opzelura; Incyte) in atopic dermatitis (AD), while late-breaking research highlighted its potential efficacy in prurigo nodularis (PN). | Image Credit: Ольга Тернавская - stock.adobe.com

Approvals and Clinical Trial Advancements

Ruxolitinib cream, a topical Janus kinase (JAK) 1/2 inhibitor, was initially approved by the FDA as a treatment for AD in September 2021.1 This was based on data from the TRuE-AD (Topical Ruxolitinib Evaluation in AD) clinical trial program, consisting of TRuE-AD1 (NCT03745638) and TRuE-AD2 (NCT03745651). These phase 3 studies found that patients experienced significantly clearer skin and itch reduction when treated with ruxolitinib cream 1.5% twice daily vs nonmedicated cream.

In July 2022, ruxolitinib cream 1.5% received additional approval for the treatment of vitiligo, becoming the first therapy to receive FDA approval for repigmentation in this patient population.2 This was supported by data from the TRuE-V1 (NCT04052425) and TRuE-V2 (NCT04057573) studies.

Incyte has since launched the TRuE-PN clinical trial series, consisting of the TRuE-PN1 (NCT05755438) and TRuE-PN2 (NCT05764161) trials, to examine the safety and efficacy of ruxolitinib cream for management of PN in adult patients.

Long-Term Safety of Ruxolitinib Cream in Atopic Dermatitis

The first poster expanded upon findings from the TRuE-AD clinical trial program by further investigating the long-term safety of ruxolitinib cream in patients with AD, with a focus on exposure-adjusted incidence rates (EAIRs) of adverse events (AEs) in the JAK inhibitor class warning.3

In the US, JAK inhibitors have a class warning for serious infections, malignancies, thromboembolic events, mortality, and major adverse cardiovascular events (MACE) when used to treat inflammatory conditions. The researchers noted that no causal relationship has been identified so far between ruxolitinib cream and AEs associated with this warning, but they conducted a study to evaluate this further.

They calculated EAIRs among patients who applied 0.75% or 15% ruxolitinib cream twice per day using data from the TRuE-AD1 and 2 studies and compared with literature-reported values for a population with AD. More specifically, EAIRs were calculated as the number of patients experiencing the event per 100 person-years (PY) of exposure.

Lawrence Eichenfield, MD, of Rady Children’s Hospital, one of the study’s investigators, summarized its findings in an on-site interview with The American Journal of Managed Care®.

“This was a very positive paper for topical ruxolitinib, showing that cutaneous infections were actually lower in the topical ruxolitinib group than would be expected,” he said. “Instead of increasing infections, it decreased infections. Many of the adverse events of interest or concern with a systemic JAK inhibitor, we don't really see signs of them being bigger issues over time."

More specifically, adults and adolescents with AD who applied 0.75% (n = 601; 441.9 PY) or 1.5% (n = 598; 466.0 PY) ruxolitinib cream experienced low EAIRs, or less than 1 patient per 100 PY, of AEs in the JAK inhibitor class warning and the rates were generally consistent between strengths.

Both groups experienced similar instances of serious infections, nonmelanoma skin cancer, MACE, and thromboembolic events, and other malignancies. However, the researchers considered these events unrelated to treatment as patients often had risk factors for such events; they typically resolved without treatment interruption.

Treatment Patterns, Impact of Ruxolitinib Cream in AD

To further describe the impact of ruxolitinib cream on patients with AD, the second poster described treatment patterns 6 months before and 6 and 12 months after initiating ruxolitinib cream among those with or without prior biologic therapy use.4

The retrospective, observational study used data from the Healthcare Integrated Research Database, spanning October 1, 2021, to March 31, 2022, to identify eligible new ruxolitinib cream users. Of the 556 included patients, 125 received biologics during the baseline period.

The researchers found that the mean (SD) number of ruxolitinib cream fills was reduced in months 7 through 12 vs months 1 through 6 of follow-up among patients both with (0.6 [1.04] vs 1.6 [1.08]) and without (0.4 [0.89] vs 1.6 [1.14]) prior biologic use. During the 12 months of follow-up, the mean (SD) number of fills was 2.2 (1.90) for patients with prior biologic experience and 2.0 (1.73) for patients without prior biologic experience, indicating that overall use remained relatively stable.

Additionally, patients who received biologics at baseline reduced their use of topical corticosteroids, topical calcineurin inhibitors, and topical PDE-4 inhibitors by 42%, 70%, and 85%, respectively, during months 7 to 12 of follow-up. The researchers emphasized that a similar reduction in topical AD treatment use was observed among those who did not receive biologics at baseline.

Similarly, from baseline to months 7 to 12 of follow-up, oral corticosteroid doses were reduced by 50% and 41% among patients who received biologics and those who did not receive biologics, respectively.

Lastly, 26% of patients who received biologic therapy during baseline did not continue biologics during months 7 to 12 of the follow-up period, an increase from 16% in the first 6 months. Similarly, more than 90% of patients who did not receive biologic therapy during baseline remained off biologics during follow-up.

Therefore, ruxolitinib cream may reduce the need for other topical treatments and biologics in patients with AD, as demonstrated by a decrease in the use of other therapies during the 12-month follow-up.

Efficacy of Ruxolitinib Cream in PN

Data from TRuE-PN1 were presented at this morning’s late-breaking session by Shawn Kwatra, MD, FAAD, of the University of Maryland, one of the study's investigators.5 He shared that the study met its primary end point, demonstrating that significantly more patients with PN who applied ruxolitinib cream 1.5% achieved a 4-point or greater improvement from baseline in Worst-Itch Numeric Rating Scale (WI-NRS4) at week 12 vs the control group (44.6% vs 20.6%; P = .0003). Similarly, significantly more patients who applied ruxolitinib cream 1.5% vs those in the control group achieved WI-NRS4 at week 4 (29.7% vs 12.7%; P = .0034).

Also, significant itch improvements were observed with ruxolitnib cream vs vehicle control at day 7 (22.4% vs 8.0%; P = .0064). In addition, the study met all key secondary end points. More specifically, ruxolitinib cream achieved an Investigator’s Global Assessment for Stage of Chronic Prurigo Treatment Success (IGA-CPG-S-TS) vs vehicle control at week 12 (15.8% vs 3.9%; P = .0048). Therefore, significantly more patients using ruxolitinib achieved overall treatment success (11.8% vs 2.9%; P = .0164).

Additionally, Kwatra debuted topline data from the TRuE-PN2 trial, which also indicated a strong positive trend across all key secondary end points, particularly for IGA-CPG-S-TS at week 12 and WI-NRS4 at day 7 (P < .05 for both). Although the primary end point was in favor of ruxolitinib cream, it did not reach statistical significance. However, based on current data, Kwatra concluded by expressing confidence in ruxolitinib cream.

“Overall, ruxolitnib cream may be a novel approach to the treatment of PN,” he said.

References

1. AJMC staff. Ruxolitinib cream approved for short-term treatment of atopic dermatitis. AJMC. September 22, 2021. Accessed March 8, 2025. https://www.ajmc.com/view/ruxolitinib-cream-approved-for-short-term-treatment-of-atopic-dermatitis
2. Gavidia M. FDA approves ruxolitinib cream as first repigmentation therapy for vitiligo. AJMC. July 19, 2022. Accessed March 8, 2025. https://www.ajmc.com/view/fda-approves-ruxolitinib-cream-as-first-repigmentation-therapy-for-vitiligo
3. Simpson EL, Kircik L, Eichenfield LF, et al. Long-term safety of ruxolitinib cream in adults and adolescents with mild-to-moderate atopic dermatitis: adverse events of interest from the TRuE-AD1 and TRuE-AD2 phase 3 studies. Poster presented at: 2025 AAD Annual Meeting; March 7-11, 2025; Orlando, FL. Abstract 64524.
4. Liu J, Desai K, Teng CC, et al. Association of ruxolitinib cream initiation with reduction in use of other topical treatments, oral corticosteroids, and biologics for atopic dermatitis, regardless of previous use of biologics. Poster presented at: 2025 AAD Annual Meeting; March 7-11, 2025; Orlando, FL. Abstract 64526.
5. Kwatra S. Efficacy and safety of ruxolitinib cream in patients with prurigo nodularis: results from a phase 3, randomized, vehicle-controlled study (TRUE-PN1). Abstract presented at: 2025 AAD Annual Meeting; March 7-11, 2025; Orlando, FL.