WCD 2023: Updates on abrocitinib’s efficacy in moderate-to-severe atopic dermatitis

Janus kinase (JAK) inhibition has emerged as a novel approach in systemic treatment of moderate-to-severe atopic dermatitis (AD). This article summarizes results of select phase III studies of the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) global development programme investigating the safety and efficacy of abrocitinib, a selective JAK1 inhibitor, in patients with moderate-to-severe AD, which were presented at the 25th World Congress of Dermatology (WCD) held in Singapore.

More time in state of efficacy with abrocitinib vs dupilumab
Two phase III, randomized, doubleblind, double-dummy controlled trials, JADE DARE and JADE COMPARE, previously demonstrated that oral abrocitinib given at 200 mg QD was associated with early itch relief and rapid skin clearance vs subcutaneous (SC) dupilumab, an anti–interleukin-4 receptor-α antibody given at 300 mg Q2W, in adult patients with moderate-to-severe AD who required systemic therapy or had inadequate response to topical medications. [Lancet 2022;400:273-282; N Engl J Med 2021;384:1101-1112]

“Over time, however, the overall treatment effects for certain outcomes became similar between dupilumab and abrocitinib,” commented Dr Claire Clibborn, Senior Director and Global Medical Strategy Head – Dermatology at Pfizer. “The different kinetics of response to abrocitinib and dupilumab suggest different durations of response to these treatments over time." [Thyssen JP, et al, WCD 2023]

A post hoc analysis of pooled JADE DARE and JADE COMPARE results compared time spent in efficacy response state in weeks 2–16 in adult patients who received oral abrocitinib 200 mg QD or SC dupilumab 300 mg Q2W. [Thyssen JP, et al, WCD 2023] The endpoint assessed improvements in Eczema Area and Severity Index (EASI), Investigator’s Global Assessment (IGA) response, Peak Pruritus Numerical Rating Scale (PP-NRS), skin pain score, and Dermatology Life Quality Index (DLQI) score.

“Overall, in weeks 2–16, adult patients treated with abrocitinib 200 mg QD spent more time [difference, 9–16 days] in a state of efficacy response vs those treated with dupilumab across measures of clinical signs of AD,” reported Clibborn. (Figure)

“From patients’ perspective, it is important to spend more time [enjoying] better health and deeper response states, even though some efficacy outcomes became similar between dupilumab and abrocitinib over time,” commented Dr Erman Guler, Global Medical Director at Pfizer.

Continuous and flexible dosing of abrocitinib effective in AD
The long-term efficacy of abrocitinib’s continuous and flexible dosing regimen was evaluated in a post hoc analysis of JADE EXTEND, an ongoing, open-label, phase III extension study that involved eligible participants with moderate-to-severe AD from six qualifying studies in the JADE programme. [NCT03422822; Silverberg JI, et al, WCD 2023]

In this analysis, JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE COMPARE (NCT03720470), JADE TEEN (NCT03796676) and JADE DARE (NCT04345367) comprised the continuous abrocitinib 200 mg group. The variable dosage population included participants from JADE REGIMEN (NCT03627767) who responded to a 12-week abrocitinib 200 mg induction, were subsequently randomized to receive abrocitinib 100 mg during a maintenance period of up to 40 weeks, experienced a flare, received rescue treatment with abrocitinib 200 mg plus topical corticosteroids (TCS) for 12 weeks, and thereafter were allocated to receive abrocitinib 100 mg with or without TCS in JADE EXTEND. [J Am Acad Dermatol 2022;86:104-112; NCT03422822; Silverberg JI, et al, WCD 2023]

“This is the first analysis to include multiple treatment escalations and de-escalations for a systemic therapy in AD, which is an important demonstration of the efficacy of a flexible dosing regimen,” Guler noted. [Silverberg JI, et al, WCD 2023]

Assessment of clinical responses over the first 48 weeks showed that substantial proportions of patients in both the continuous treatment and flexible dosing groups achieved clinically meaningful and sustained improvements in skin clearance (50 percent improvement in EASI from baseline [EASI-50]: 94 percent and 87 percent; 75 percent improvement in EASI from baseline [EASI-75]: 82 percent and 69 percent), and itch (≥4-point improvement from baseline in PP-NRS [PP-NRS4]: 67 percent and 44 percent).

Abrocitinib in Asian patients
“We also conducted an interim post hoc analysis of JADE EXTEND to assess the long-term efficacy of abrocitinib across different racial subgroups,” said Professor Andrew Alexis of the Weill Cornell Medical College in New York, US. [Kircik LH, et al, WCD 2023]

In the analysis (data cut-off, 25 September 2021), eligible patients who were randomized to receive abrocitinib 100 mg or 200 mg in the phase III JADE MONO-1, JADE MONO-2, JADE COMPARE, JADE TEEN, and JADE DARE trials continued to receive the same dose in JADE EXTEND. Race (ie, White, Black, Asian) was self-reported by patients at initial screening visit.

Based on the proportion of patients achieving an IGA score of 0 (clear) or 1 (almost clear) with a ≥2-grade improvement from baseline, EASI-75, PP-NRS4, and ≥4-point improvement from baseline in the Patient-Oriented Eczema Measure between week 2 and week 48, abrocitinib treatment was associated with clinically meaningful improvements in AD signs and symptoms, including itch, in substantial proportions of patients with moderate-to-severe AD across the racial subgroups, including the Asian population.

“While AD is a heterogeneous disease with endotype profiles that differ by race, these results show that abrocitinib treatment remains an effective option for Asian patients,” concluded Alexis. [J Allergy Clin Immunol 2019;143:1-11; Kircik LH, et al, WCD 2023]

Abrocitinib’s safety profile
In JADE EXTEND, abrocitinib showed a manageable long-term safety profile. With a median of 10.4 months of abrocitinib exposure, rates of treatment-emergent adverse events (TEAEs) were 75.5 percent and 82.0 percent in the 100 mg (n=595) and 200 mg (n=521) groups, respectively. Corresponding rates of serious TEAEs were 4.7 percent and 7.1 percent. [J Eur Acad Dermatol Venereol 2023;doi:10.1111/jdv.19280]

Summary
Results from post hoc and interim analyses of select JADE studies support the use of abrocitinib for early and sustained responses in patients with moderate-to-severe AD requiring systemic therapy. Long-term data further confirm abrocitinib’s efficacy in both continuous and flexible dosing regimens, and across racial subgroups.