Ruxolitinib cream: a safe treatment for elderly AD patients

The efficacy assessment of ruxolitinib 1.5% cream in elderly patients with atopic dermatitis (AD) discovered an Investigator’s Global Assessment (IGA) treatment success rate of 60.5% after 8 weeks. This subanalysis of 2 phase 3 trials also revealed substantial improvements in itch and sleep.

Janus kinases (JAK) modulate type 2 cytokines involved in the pathogenesis of AD, and ruxolitinib selectively inhibits JAK1 and JAK2 [1]. The results of the phase 3 trials TRuE-AD1 (NCT03745638) and TRuE-AD2 (NCT03745651) demonstrated sustained action of ruxolitinib cream on inflammation and itch in AD compared with a vehicle, with a good safety profile. The studies tested ruxolitinib 0.75% and 1.5% cream versus vehicle with the primary endpoint of treatment success in the IGA defined as a score 0/1 with at least 2 grades of improvement from baseline.

“Published literature describing patients with AD aged 65 years and older is limited,” said Prof. Jacek Szepietowksi (Wroclaw Medical University, Poland) [2]. Thus, Prof. Szepietowksi and colleagues assessed the efficacy and safety of the topical JAK1/JAK2 inhibitor ruxolitinib in this population at week 8 with pooled data of the ≥65-year-old patients from TRuE-AD1 and TruE-AD2 [2].

Among the 1,249 original participants (aged 12–85 years), 115 (9.2%) were included in the presented analysis. The median age of this older cohort was 70 years and 55.7% were women. The clinical characteristics showed a mean baseline Eczema Area and Severity Index (EASI) score of 7.7 and IGA of 3 (i.e. moderate) in 73% of participants. Prof. Szepietowksi added that “70% of patients had an itch numeric rating scale (NRS) score of at least 4 and the median duration of AD was 20 years, indicating long-standing disease.”

The primary endpoint of IGA 0/1 was achieved by 60.5% in the 1.5% ruxolitinib cream arm, which was significantly more than the 15.4% receiving vehicle (P<0.001). The 0.75% regimen led to IGA 0/1 in 32% of patients. Also, the 8-week results for EASI 50, 75, and 90 reflected time-dependent and dose-dependent ameliorations. EASI 50 was reached by 64% (0.75% dosage) and 84.2% (1.5% dosage) versus 38.5% on placebo. The corresponding outcomes for EASI 75 were 44.0% and 73.7% versus 15.4%, respectively. EASI 90 was seen in 26% and 50% of the respective active treatment arms versus 3.8% on the vehicle.

Among the key secondary endpoints were differences in itch NRS score and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance. Depending on the cream concentration, a proportion of 53.8% (1.5% cream) and 36.1% (0.75% cream) had a ≥4-point score reduction in itch NRS compared with 17.6% in the placebo group. As for a decrease in sleep disturbance, about a third in the higher-dosed arm experienced a ≥6-point decrease in their PROMIS score.

Prof. Szepietowksi pointed out that in terms of safety, ruxolitinib cream only led to a low rate of application site reactions and no safety findings of systemic JAK inhibition. He furthermore stressed that no serious treatment-emergent adverse events were observed. “These results demonstrate the potential of ruxolitinib cream as an effective and well-tolerated topical treatment for patients with AD aged 65 years and older,” Prof. Szepietowksi concluded.

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   1. Papp K, et al. J Am Acad Dermatol. 2021 Oct;85(4):863-872.
   2. Szepietowski JC. Efficacy and safety of ruxolitinib cream among patients aged ≥65 years with atopic dermatitis: pooled results from two phase 3 studies. FC01.01, EADV Congress 2021, 29 Sept–2 Oct.

 

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Posted on 18 November 202118 November 2021