Assessing treatment effect of baricitinib in atopic dermatitis using digital endpoints derived from actigraphy data: nocturnal scratch and sleep disturbance

Persistent itch and the itch-scratch cycle lead to burden in atopic dermatitis (AD), including skin damage, potential secondary infection, worsening inflammation, and sleep disturbance. These impact patient quality of life. In clinical trials, itch and sleep are typically assessed using patient reported outcomes (PROs), which are influenced by recall bias and subjectivity. Objective digital endpoints assessing nocturnal scratch and sleep quality can provide additional insights to complement PROs. In two pivotal phase 3 monotherapy studies evaluating the safety and efficacy of baricitinib in adult patients with moderate to severe AD (BREEZE-AD1 and -AD2)1, actigraphy data was collected using the GENEActive wearable device by Activinsights. We deployed analytically validated algorithms2 to derive digital endpoints from the raw actigraphy data from a total of 664 patients from baseline to week 4 after first dose. The digital endpoints include nocturnal scratch duration and intensity, percent time asleep, and wakefulness after sleep onset. Results demonstrated that nighttime sleep is moderately correlated with nocturnal scratch (r=0.45) and about 25% variation in sleep is explained by nocturnal scratch. Conversely, digital measures in nocturnal scratch and sleep are weakly correlated (<0.35) with PROs for itch and sleep disturbance. Digital endpoints demonstrated value in detecting treatment response. On average, hourly scratch duration reduced by 21.6 seconds (32% reduction), and wake after sleep onset time from each night reduced by 14 minutes (14% improvement) in the baricitinib 4 mg arm compared to placebo at week 4. Digital measures did not show any improvement in placebo patients; by contrast placebo effect was apparent in PRO measures. In summary, although not routinely used and still an evolving technology, compared to PROs, objective digital endpoints can provide additional insights into treatment benefit. 1Br J Dermatol. 2020;183(2):242-255. 2NPJ Digital Med. 2023; 6(1):72.