Abrocitinib effectively manages AD flares

Rescue therapy using the Janus kinase 1 inhibitor abrocitinib combined with topical medicated therapy recaptured efficacy responses and had a favourable safety profile in individuals with moderate-to-severe atopic dermatitis (AD) who experienced flare during the maintenance period of the phase III randomized-withdrawal JADE REGIMEN trial.

This trial enrolled participants with moderate-to-severe AD* who had inadequate response or intolerance to topical medications or required systemic therapy for controlling AD. During the open-label induction phase, 1,233 participants received oral abrocitinib 200 mg QD for 12 weeks. Following which, those who responded** to induction therapy (n=798) entered a 40-week maintenance phase wherein they were randomized 1:1:1 to either continue with the induction dose (continuation arm), reduce their dose to 100 mg (reduction arm), or withdraw from the drug and transition to placebo (withdrawal arm).

During the maintenance phase, 16, 39, and 76 percent of patients in the respective continuation, reduction, and withdrawal arms stopped responding to treatment and experienced protocol-defined flares***. As such, the team evaluated the efficacy and safety of rescue therapy among these individuals using abrocitinib 200 mg plus medicated topical therapy^# for 12 weeks. [AAAAI 2022, abstract 032]

After 12 weeks of rescue therapy, more than half of participants who withdrew from abrocitinib during the maintenance phase managed to recapture their IGA, EASI, and PP-NRS scores (74, 57, and 68 percent, respectively). About a third of those who continued with the induction dose recaptured these efficacy scores (36, 33, and 29 percent, respectively). The corresponding recapture rates in the dose reduction arm were 51, 32, and 40 percent.

The continuation arm had the greatest fraction of participants reporting any adverse events (AEs) during the rescue period (56 percent). The reduction and withdrawal arms had similar rates of any AEs (31 percent and 34 percent, respectively). Rates of severe AEs were low across all arms (5, 2, and 2 percent for the continuation, reduction, and withdrawal arms, respectively), as were the rates of discontinuations owing to AEs (5, 3, and 1 percent, respectively).

The most frequently reported treatment-emergent AE (TEAE) of any cause (>5 percent in any treatment arm) with abrocitinib during the rescue phase were nasopharyngitis (7 percent [200 mg] and 6 percent [100 mg]) and atopic dermatitis (7 percent and 4 percent, respectively). In the withdrawal arm, the most common TEAE was upper respiratory tract infection (8 percent). Herpes zoster was the most frequent TEAE of special interest tied to abrocitinib (5 percent and 4 percent, respectively).

“Nonetheless, most AEs in the rescue period were mild-to-moderate regardless of treatment,” said Dr Jonathan Silverberg from The George Washington University School of Medicine and Health Sciences, Washington, DC, US, during his presentation.

AD is a long-term, relapsing-remitting disease by nature hence the need for flexibility in treatment (ie, dose reduction, treatment interruption). [Ann Allergy Asthma Immunol 2018;120:10-22] “This post hoc analysis of JADE REGIMEN examined how well rescue therapy recaptured efficacy responses, defined as achieving a score not worse than the score at randomization baseline,” said Silverberg.

“[Our findings show that] a significant proportion of patients who experienced flare during the maintenance period of JADE REGIMEN recaptured efficacy responses with 12 weeks of rescue therapy with abrocitinib 200 mg plus topical medicated therapy with an overall acceptable safety profile,” he concluded.