The benefits of corticosteroid cream decline over time, but there may be a new treatment option on the horizon.
Evidence is growing in support of the first topical JAK inhibitor approved by the US FDA for the treatment of mild to moderate atopic dermatitis.
The results of phase III trials of ruxolitinib cream, published in the Journal of the American Academy of Dermatology, reveal the cream can provide rapid and sustained relief from itch associated with atopic dermatitis in patients who have not responded to other treatments.
Australian dermatologists are watching with interest to see whether the ruxolitinib cream (Opzelura, Incyte) is going to make its way to Australia.
Melbourne dermatologist Professor Rod Sinclair said the latest study showed strong results in treating the itch associated with atopic dermatitis.
“It will be interesting to see whether the TGA gets an application for the cream,” he said.
In September 2021, ruxolitinib was approved by the FDA for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.
In the latest paper, researchers said itchiness has been reported by those with atopic dermatitis as the most burdensome symptom which affects sleep, work productivity and overall quality of life. The chronic inflammatory skin disease responded to the antipruritic and anti-inflammatory activity of ruxolitinib cream.
They undertook two identical, double-blind, randomised trials with 1200 subjects using either 0.75% ruxolitinib cream, 1.5% ruxolitinib cream or a placebo cream. All creams were applied twice daily over continuous eight-week periods.
Itch was evaluated using the five-point Investigator’s Global Assessment scale and the studies aimed to attain a ≥2 point improvement at eight weeks from baseline. At eight weeks, 50% of 0.75% ruxolitinib users, 53.8% of 1.5% ruxolitinib users, and 15% of placebo users reached this level of improvement.
Additionally, those using 1.5% ruxolitinib experienced significant reduction in itch within 12 hours of application. An itch-free state was reached 36 hours after application and was sustained throughout the eight-week trial period.
Corticosteroid creams such as hydrocortisone are the standard treatment for atopic dermatitis, but evidence suggests the initial benefit can diminish quickly due to tachyphylaxis.
In contrast, this study found the efficacy of ruxolitinib cream did not decrease over the eight-week trial periods, but longer-term effects have yet to been evaluated. Most clinical trials for corticosteroid topical treatments evaluate short courses of four weeks or less, the authors reported.
The long-term toxicity has not been evaluated, but local adverse effects including reversible skin thinning and atrophy as well as irreversible telangiectasiae and striae distensae have been reported with persistent use. Randomised trials of 16-24 weeks have shown no evidence of long-term systemic affects from intermittent topical corticosteroid use.
Ruxolitinib also comes in an oral form and is used to treat adults with myelofibrosis, adults with polycythemia vera, and patients 12 years and older with graft-versus-host disease. It has been approved for used in Australia by the TGA and is marketed by Novartis Pharmaceuticals under the brand name Jakavi.
Use of ruxolitinib in combination with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants, such as azathioprine or cyclosporine, is not recommended. The cream does come with a black box warning from the FDA.
Dermatology Republic contacted Incyte for comment about whether an application has been made to the Australian regulator, but the manufacturer had not responded at the time of publication.
The cream was also approved by the FDA in July for the topical treatment of nonsegmental vitiligo in patients aged 12 years and over.
This approval was based on data from the phase III TRuE-V clinical trial program (TRuE-V1 and TRuE-V2), evaluating the safety and efficacy of ruxolitinib compared to a placebo vehicle in more than 600 people with nonsegmental vitiligo. In the studies, treatment with ruxolitinib resulted in significant improvements in Vitiligo Area Scoring Index (VASI) scores, which represent improvements in facial and total body repigmentation at week 24 (primary analysis) compared to non-medicated cream and in an open-label extension at week 52.
Journal of the American Academy of Dermatology 2022, online 14 September
