results from a long-term analysis of clinical trial data showed.
Dr. Kim A. Papp
“The incidence of application-site reactions was low, and there were no clinically meaningful changes or trends in hematologic parameters,” Kim Papp, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium.
Ruxolitinib cream is a selective Janus kinase 1/JAK2 inhibitor being developed by Incyte for the treatment of atopic dermatitis (AD).
According to a press release from the company, the Food and Drug Administration has extended the New Drug Application review period for the agent by 3 months to September 2021. If approved, it would become first topical JAK inhibitor for use in dermatology.
In two phase 3, randomized studies of identical design involving 1,249 patients aged 12 and older with AD – TRuE-AD1 and TRuE-AD2 – ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. To be eligible for the trials patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks.
A recently published report found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).
Longterm data
During the symposium, Dr. Papp presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Those initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen. They were instructed to treat skin areas with active AD only and to stop treatment 3 days after clearance of lesions, and to restart treatment with ruxolitinib cream at the first sign of recurrence. Safety and tolerability were assessed by frequency and severity of adverse events, while disease control was measured by the proportion of patients with an IGA score of 0 or 1 and the affected BSA.
Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1 to 60%-77% and 72%-80% in TRuE-AD2.
The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.
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In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.
“The most common treatment adverse events were upper respiratory tract infections and nasopharyngitis,” Dr. Papp said. “When looking at exposure-adjusted adverse events, we see that there is a high degree of similarity between any of the TEAEs across all of the treatment groups in both studies. We also see that it was patients on the vehicle who experienced the greatest number of application-site reactions.”
Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.