Upadacitinib delivers sustained PRO improvements in AD

Data presented at AAD 2023 underpin the potential of upadacitinib, a selective Janus kinase inhibitor, to provide long-term improvements in patient-reported outcomes (PROs; skin symptoms, sleep, and quality of life [QoL]) in individuals with moderate-to-severe atopic dermatitis (AD).

“While upadacitinib improved PROs through 16 weeks, the long-term impact of sustained upadacitinib on PROs has not been comprehensively evaluated,” noted the researchers, led by Dr Jonathan Silverberg from the George Washington University School of Medicine and Health Sciences, Washington, DC, US.

As such, Silverberg and colleagues set off to evaluate the long-term effects of once-daily oral upadacitinib on PROs using data from the phase III Measure Up 1, Measure Up 2, and AD Up studies. A total of 2,584 participants were randomized 1:1:1 to upadacitinib 15 or 30 mg or placebo. By week 16, placebo recipients were re-randomized 1:1 to either upadacitinib arm. The study drug was to be taken alone (Measure Up studies) or with concomitant topical corticosteroids (AD Up).

Outcomes were the percentage of participants achieving a predefined clinically meaningful improvement (ie, reduction from baseline) and a minimal severity score across PROs. [AAD 2023, abstract 42262]

 

PRO improvements

As early as week 2, up to ≥40 percent of participants treated with either dose of upadacitinib achieved clinically meaningful improvement across all PROs.

By week 16, about half of those receiving upadacitinib 15 mg achieved clinically meaningful improvement in most PROs. In the upadacitinib 30-mg arm, nearly three-quarters achieved these improvements.

Week 52 generally saw greater improvements compared with week 16. Up to 64 percent of patients treated with upadacitinib 15 mg and about 71 percent of those taking the higher dose had improvements in patient-reported itch (WP-NRS* ≥4).

For sleep (ADerm-IS** Sleep ≥12), improvement rates for upadacitinib (either dose) were between 74 and 83 percent.

Up to 90 percent of participants on upadacitinib 15 mg reported having QoL improvements (DLQI*** ≥4). The rate in the upadacitinib 30-mg arm was higher by 4 percent.

Other PRO parameters that improved consistently from week 16 to 52 with either upadacitinib dose are ADerm-SS Skin Pain ≥4 and ADerm-IS Daily Activities ≥14.

 

Minimal severity in PROs

A similar trend was seen in terms of the percentage of patients achieving minimal severity in PROs. “Scores representing minimal severity of PROs were rapidly achieved by week 2 among patients receiving [upadacitinib 15 and 30 mg (≥10 and ≥15 percent in all PROs)] based on the observed cases,” noted Silverberg and colleagues.

“The proportion of patients achieving minimal severity at week 52 with upadacitinib was higher for multiple PROs than the proportion of patients achieving minimal severity at week 16,” they continued.

These were represented by the fractions of participants achieving WP-NRS 0–1, ADerm-IS 0–3, and DLQI 0–1 with the lower upadacitinib dose at week 52 (41, 62, and 35 percent, respectively). The corresponding rates with upadacitinib 30 mg were 50, 71, and 46 percent. The week-16 rates were generally lower by roughly 4–12 percent.

 

Rapid, sustained efficacy

“Patients who initially received placebo and were re-randomized to upadacitinib experienced similar improvements in PROs as did those who initially received upadacitinib … The improvements in PROs with upadacitinib were also consistent with or without background topical corticosteroids.,” they added.

“[Taken together,] these results support the rapid and sustained efficacy of once-daily oral upadacitinib in reducing itch and other AD symptoms and improving sleep and QoL of patients with AD,” said the researchers.