Ruxolitinib Cream Offers Safe, Durable Option for Patients with Atopic Dermatitis

Linda Stein Gold, MD
Credit: Henry Ford Health

The advent of nonsteroidal topicals, such as ruxolitinib cream (Opzelura) has been a breakthrough welcomed by dermatologists treating atopic dermatitis and patients alike.

Offering the potential for efficacious treatment with an established safety profile, options, such as the topical JAK inhibitor, have grown in popularity since the first approval for a topical nonsteroidal topical option received approval from the US Food and Drug Administration (FDA) more than 2 decades ago.^1,2

“Ruxolitinib cream fulfills an important unmet need for topical therapy of mild to moderate atopic dermatitis. In the past, nonsteroidal options did not have the efficacy that we saw with topical corticosteroids,” said Linda Stein Gold, MD, Director of Dermatology Clinical Research at Henry Ford Health System, in an interview with HCPLive. “In addition, topical corticosteroid therapy is what I consider a short-term solution to a long-term problem. The use of potent [topical corticosteroids] can be used only for a limited duration and are not appropriate for sensitive areas including the face, skin folds or groin. Often, patients would receive multiple prescriptions for different body sites and for different durations of therapy.”

With long-term topical corticosteroid use associated with increased risk for several adverse events and outcomes, the dermatology community looked forward for years to a world where their armamentariums included a nonsteroidal topical option for management of atopic dermatitis, as well as other dermatologic conditions. Although the first calcineurin inhibitors received approval from the FDA in 2000, as Stein Gold notes, the options preceding the approval of ruxolitinib cream in September 2021 meant many users still failed to achieve optimal control of their atopic dermatitis.^1,2

The approval of ruxolitinib cream in September 2021 marked the first topical formulation of a JAK inhibitor approved in the US and indicated the agent for short-term and noncontinuous chronic treatment of mild to moderate atopic dermatitis in nonimmunocompromised patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable. The approval was based on data from the Topical Ruxolitinib Evaluation in Atopic Dermatitis (TRuE-AD) clinical trial program, which included the phase 3 TRuE-AD1 and TRuE-AD 2 trials.¹

Both designed as randomized, double-blind, vehicle-controlled Phase 3 studies, TRuE-AD1 and TRuE-AD 2 enrolled patients aged 12 years or older with atopic dermatitis for 2 or more years, an Investigator's Global Assessment (IGA) score of 2/3, and 3% to 20% affected body surface area. A total of 1249 patients were randomized 2:2:1 to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks. Of these, 1208 were analyzed for efficacy.^3,4

Pooled analysis of the trials suggested use of ruxolitinib was associated with a significantly greater proportion of patient’s achieving the primary endpoint of IGA-TS at week 8. Specifically, the primary endpoint was achieved by 44.7% of the 0.75% ruxolitinib cream group, 52.6% of the 1.5% ruxolitinib cream group, and 11.5% of the vehicle group (P for all <.0001).^3,4

Pooled safety data from the trials suggested 15 patients discontinued from the studies because of a treatment-emergent adverse event, with 8, 4, and 3 patients discontinuing from the vehicle, 0.75% ruxolitinib cream, and 1.5% ruxolitinib cream groups, respectively. Further analysis of safety data indicated serious treatment-emergent adverse events were reported among 0.8%, 0.6%, and in 0.8% of the 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, and vehicle groups, but none of the observed were considered related to treatment with ruxolitinib cream.^3,4

“Ruxolitinib cream has proven efficacy that surpasses a mid-potent topical corticosteroid. It is appropriate for treatment of up to 20% body surface area and for short term and non-continuous long-term treatment of mild to moderate atopic dermatitis in patients aged 12 and older,” Stein Gold remarked. “We saw a good safety profile from long-term clinical trials. One surprising attribute of ruxolitinib is the favorable tolerability profile which we have not had with traditional non-steroidal options.”

Since receiving approval, ruxolitinib cream has found a welcomed role within treatment algorithms for thousands of patients with atopic dermatitis. An analysis published in March 2024 within the American Journal of Clinical Dermatology shed light on safety of the agent in real-world settings using data recorded within the Incite global safety database and US FDA Adverse Event Reporting System from approval through September 2022.⁵

From the databases, which included data from patients using the cream as treatment for vitiligo, investigators obtained an estimated 13,833 patient-years of treatment during the first year of approval for ruxolitinib cream. A total of 589 events were received for ruxolitinib cream during the time period. Investigators found 99.3% of events were considered nonserious in nature, with only 4 serious adverse events and 0 fatal adverse events.⁵

Of the 589 reported events, 55.9% were considered “special situation events" and 44.1% were adverse events. The 4 serious adverse events were 2 cases of skin cancer, 1 case of pericarditis, and 1 case of thrombocytopenia, but none of these cases had sufficient information to assess possible relatedness to ruxolitinib cream. Further analysis of serious adverse events indicated none of the serious adverse events associated with the class warnings for JAK inhibitors were reported.

“Overall, I use ruxolitinib as ‘one-stop shopping’ to simplify the treatment regimen and set my patients up for success with taking control of their treatment,” Stein Gold added.

References:

1. Incyte. Incyte announces U.S. FDA approval of OpzeluraTM (ruxolitinib) cream, a topical jak inhibitor, for the treatment of atopic dermatitis (AD). Incyte. September 21, 2021. Accessed October 1, 2024. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-us-fda-approval-opzeluratm-ruxolitinib-cream.
2. Carr WW. Topical calcineurin inhibitors for atopic dermatitis: review and treatment recommendations. Paediatr Drugs. 2013;15(4):303-310. doi:10.1007/s40272-013-0013-9
3. Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol. 2021;85(4):863-872. doi:10.1016/j.jaad.2021.04.085
4. Pooled results from Incyte’s true-AD1 and true-AD2 atopic dermatitis studies of ruxolitinib cream show clinically meaningful improvements in patient-reported quality of life assessments. BioSpace. October 29, 2020. Accessed October 1, 2024. https://www.biospace.com/pooled-results-from-incyte-s-true-ad1-and-true-ad2-atopic-dermatitis-studies-of-ruxolitinib-cream-show-clinically-meaningful-improvements-in-patient-reported-quality-of-life-assessments.
5. Hu W, Thornton M, Livingston RA. Real-World Use of Ruxolitinib Cream: Safety Analysis at 1 Year. Am J Clin Dermatol. 2024;25(2):327-332. doi:10.1007/s40257-023-00840-1