Safety data supports ruxolitinib for long-term treatment of atopic dermatitis

Ruxolitinib cream demonstrated efficacy and tolerability in patients with atopic dermatitis during 44 weeks of as-needed treatment, according to two phase 3 trials.

“Conventional topical treatments for AD include corticosteroids, calcineurin inhibitors, and the phosphodiesterase 4 inhibitor crisaborole; however, they are associated with local adverse events, tolerability concerns or anatomic limitations, particularly when used long term,” Kim Papp, MD, PhD, FRCPC, president of Probity Medical Research in Waterloo, Ontario, Canada, and colleagues wrote. “Thus, there is an unmet need for novel topical treatments for long-term use that provide disease control without notable safety and tolerability concerns.”

The study analyzed long-term safety (LTS) and efficacy data from two double-blind phase 3 studies of ruxolitinib in the treatment of AD.

Eligible patients were aged 12 years or older with an AD duration of more than 2 years and an IGA score of 2 or 3. Patients also had a body surface area involvement of 3% to 20%, excluding the scalp.

Patients were randomly assigned 2:2:1 to treatment with 0.75% ruxolitinib cream, 1.5% ruxolitinib cream or vehicle twice daily for 8 weeks, even if there was improvement or clearing of lesions. After 8 weeks, patients in the vehicle group were randomly assigned to one of the ruxolitinib strengths, and all patients continued treatment for 44 weeks, only applying the cream to active AD areas. Of the 1,119 patients that completed the initial 8-week treatment period, 1,072 participated in the LTS period, with 831 completing the extended treatment.

In terms of efficacy, the median cumulative time off treatment due to lesion clearance during the LTS period was 38% and 44% for patients who continued treatment on 0.75% and 1.5% ruxolitinib cream, respectively, and 23% and 38% for those patients initially on vehicle who switched to 0.75% and 1.5% ruxolitinib cream.

According to the researchers, disease control was achieved by the end of the 44 weeks of LTS treatment, with 74.1% to 77.8% of patients achieving an IGA score of 0/1. Mean affected body surface area was also low at 1.4% to 1.8%.

Over the entire 52-week treatment period, treatment-emergent adverse events were reported in 67.4% of patients on 0.75% ruxolitinib cream and 62.6% of patients on 1.5% ruxolitinib cream, as well as in 53.5% of vehicle patients switched to 0.75% cream and 57.6% of vehicle patients switched to 1.5% cream. The most common adverse events included upper respiratory tract infections and nasopharyngitis.

Of these adverse events, 8.7% and 7.4% were considered treatment-related in patients on 0.75% and 1.5% ruxolitinib, respectively, whereas this rate was 2% for those who switched from vehicle to 0.75% ruxolitinib and 6.1% for those who switched from vehicle to 1.5% ruxolitinib. Neutropenia, application site pain and application site pruritis were the most common treatment-related adverse events.

“Although the frequency of [treatment-emergent adverse events] was higher in the 44-week LTS period than in the 8-week [vehicle-controlled] period, this is expected with longer follow-up,” Papp and colleagues wrote. “Both strengths of ruxolitinib cream monotherapy demonstrated effective disease control and were well tolerated in the long-term setting.”