Ruxolitinib cream safe, effective for children with atopic dermatitis
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Treatment with ruxolitinib cream was well tolerated and effective with no effect on blood counts or bone growth among children with atopic dermatitis, according to a study published in Annals of Allergy, Asthma & Immunology.
Ruxolitinib cream (Opzelura, Incyte Dermatology), a Janus kinase (JAK) inhibitor, has shown efficacy and safety among adolescents and adults with AD.
To evaluate its use among younger patients, Donald Y.M. Leung, MD, PhD, distinguished professor of pediatrics at National Jewish Health, and colleagues enrolled 71 children aged 2 to 17 years (60.6% girls; 59.2% white) with AD between Sept. 21, 2017, and Oct. 7, 2020 into the phase 1, open-label study. Patients were enrolled into six stepwise cohorts based on age (aged 12-17 years; 7 to < 12 years; 2 to < 7 years) and ruxolitinib cream strength (0.5%; 0.75%; 1.5%).
Patients applied ruxolitinib cream as a thin film topically once in the morning and again approximately an hour before bedtime for 28 days, beginning with the lower strength.
Researchers assessed safety, pharmacokinetics and efficacy at baseline, week 2 and week 4, with another safety follow-up 30 days after the last application.
Safety profile
Treatment-emergent adverse events occurred among 32.4% of the entire population, ranging from 14.3% to 50% among the stepwise cohorts.
These events included headache (5.6%); worsening, flare or exacerbation in AD (4.2%); decreased neutropenia or neutrophil count (2.8%); otitis media (2.8%); and upper respiratory tract infection (2.8%).
However, only four patients (5.6%) experienced treatment-emergent adverse events related to treatment. These events included a decreased neutrophil count, application-site urticaria, abnormal liver function test result and application-site pain, all of which were considered grade 1 or 2 and none deemed serious.
Also, researchers reported no clinically meaningful changes in mean chemistry, hematology values, vital signs or height.
Patients in cohorts 3 to 6, who ranged from aged 2 years to younger than 12 years and used 0.75% and 1.5% ruxolitinib cream, experienced large interpatient and intrapatient variability in bone biomarkers. However, the researchers did not identify any pattern of change suggesting that ruxolitinib cream affected bone growth.
Pharmacokinetics
With arithmetic mean values ranging from 23.1 nM to 97.9 nM, the researchers noted that plasma concentrations of ruxolitinib were low, and lower than the half-maximal inhibitory concentration for thrombopoietin phosphorylation of STAT3 at 281 nM, with a high level of interpatient variability. Median steady-state plasma concentration levels in the cohorts using 1.5% ruxolitinib cream ranged from 30 nM to 45 nM.
Between weeks 2 and 4, the researchers found that plasma concentrations of ruxolitinib tended to remain similar with estimated mean bioavailability ranging from 5.9% (standard deviation [SD], 3.4%) to 15% (SD, 17.7%) across cohorts.
Efficacy
All the cohorts had reductions in Eczema Area and Severity Index (EASI) scores from baseline to week 2, with mean percentage improvements continuing through week 4 for all cohorts except cohort 5 (aged 2 to < 7 years; 0.75% ruxolitinib cream).
Also, 44.4% to 81.8% of patients achieved 50% improvement in EASI scores, and 18.2% to 54.5% achieved 75% improvement.
At week 4, 22.2% to 61.5% of patients from all cohorts achieved 90% improvement in EASI scores.
All cohorts except cohort 1 (aged 12-17 years; 0.5% ruxolitinib cream) achieved Investigator Global Assessment treatment success (range, 18.2%-64.3% for cohorts 2-6) by week 2 with increases (range, 40%-84.6%) for all cohorts by week 4.
Median body surface area affected fell from 12.2% (range, 1.7%-20.4%) at baseline for all cohorts by week 2 (range, 6.1%-10%) with further decreases by week 4 (range, 2%-6%). Patient-Oriented Eczema Measure scores fell for all cohorts through week 2 (range, 3-6.7) and week 4 (range, 1.2-4.4) as well.
Mean changes in itch on a numeric rating scale showed substantial improvements in each cohort at week 2 and further maintenance or improvement at week 4.
Conclusions, next steps
The researchers concluded that children with AD tolerated and benefitted from treatment with ruxolitinib cream spanning 4 weeks of twice-daily application of 0.5%, 0.75% and 1.5% concentrations.
This treatment did not have any impact on mean blood cell counts or bone growth, with generally low plasma concentration after topical application.
The researchers noted that this treatment may benefit patients who do not respond to topical steroids, although they added that further studies of its use among children are warranted.
Perspective
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The results are very encouraging and not surprising based on adult experience. It is a great drug. It works very well in the real world, and patients note improvements in itch that are very impressive.
Personally, I think ruxolitinib can replace topical steroids, which have a lot of baggage such as steroid phobia. Also, patients often are confused as to how to use them (ie, for how long, repeated use) and have a risk for skin thinning. Ruxolitinib does not have those issues, and given its limited topical use, it has very little of the risks associated with oral JAK inhibitors at all.
Next, research should expand to other indications such as lichen planus and prurigo nodularis.
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