Abrocitinib provides early and sustained efficacy in atopic dermatitis

Abrocitinib provides early relief of itch and skin pain as well as sustained efficacy for >2 years in patients with moderate-to-severe atopic dermatitis (AD), post-hoc analyses of JADE trials have shown. Notably, long-term efficacy was observed irrespective of prior exposure to systemic therapies.

Early relief of itch and skin pain
Relief of itch and skin pain occurred as early as day 2 after initiation of abrocitinib (200 mg or 100 mg QD) treatment, and these responses often continued to increase through week 4 in a dose-dependent manner, according to a post hoc analysis of the phase III JADE COMPARE and JADE DARE trials in adults with moderate-to-severe AD. [Bewley A, et a, EADV 2024, poster P0547]

“At most time points, higher proportions of patients treated with abrocitinib 200 mg achieved efficacy responses vs all other treatment arms [including abrocitinib 100 mg QD, dupilumab 300 mg Q2W, and placebo],” the researchers reported. “A numerically higher proportion of patients achieved clinically meaningful or high thresholds of itch and skin pain relief with abrocitinib 200 mg vs dupilumab through week 4. Responses with abrocitinib 100 mg were generally comparable vs dupilumab, with overlapping confidence intervals [CIs] through week 4.”

Long-term efficacy for >2 years
Abrocitinib (200 mg or 100 mg) provided sustained long-term efficacy through 112 weeks of continuous treatment in adults and adolescents with moderate-to-severe AD, regardless of prior exposure to systemic therapies, according to a post hoc analysis of JADE EXTEND – an extension study that enrolled patients from the phase IIA JADE MOA and phase III JADE MONO-1, JADE MONO-2, JADE COMPARE, JADE TEEN and JADE DARE trials. [Gooderham MJ, et al, EADV 2024, poster P0488]

The analysis included 1,930 patients, of whom 1,054 were not previously treated with systemic therapy and 876 had prior exposure to systemic therapy (oral corticosteroids, n=446; systemic cyclosporine A [CsA], n=213; biologics, n=70; methotrexate [MTX], n=21; ≥2 systemic therapies, n=126).

“Previous exposure to systemic therapies had a modest impact on long-term abrocitinib response,” the researchers reported. “For patients with previous exposure to systemic therapies, abrocitinib 200 mg more consistently provided better skin clearance and pruritus control than abrocitinib 100 mg.”

With either dose of abrocitinib, efficacy responses were sustained through 112 weeks of continuous treatment across all subgroups of prior treatment exposure. Notably, at week 112 of abrocitinib treatment with either dose, 43.6–53.3 percent of patients with prior exposure to oral corticosteroids or systemic CsA achieved a stringent response of 90 percent improvement from baseline in Eczema Area and Severity Index (EASI-90), and 27.8–39.0 percent achieved an itch-free state. In patients with prior exposure to biologics, 28.6–45.5 percent achieved EASI-90 and 33.3 percent achieved an itch-free state with either dose of abrocitinib.

Long-term safety
Long-term treatment with abrocitinib (consistent 200 mg dosing, or flexible dosing of 200 mg for induction followed by 100 mg for maintenance and 200 mg for rescue of flares) for up to 4.1 years is well tolerated, with no new safety signals observed, an interim analysis of JADE EXTEND has shown. [Simpson EL, et al, EADV 2024, poster P0504]

Among 531 patients (consistent-dose cohort, n=266; flexible-dose cohort, n=265) included in the analysis, incidence rates (IRs) of treatment-emergent adverse events (TEAEs) of special interest, including serious infections (1.38 vs 2.25 per 100 patient-years [PYs]), all herpes zoster (HZ) infections (3.02 vs 3.95 per 100 PYs), and adjudicated opportunistic HZ infections (0.46 vs 0.90 per 100 PYs), were slightly lower, with overlapping CIs, in the abrocitinib 200 mg/100 mg flexible-dose vs 200 mg consistent-dose cohort.

Other TEAEs of special interest, including major adverse cardiovascular events (IR, 0.15 vs 0.15), venous thromboembolism events (IR, 0.15 vs 0.15), and adjudicated malignancies (excluding nonmelanoma skin cancer) (IR, 0.30 vs 0.15), were infrequent and comparable in both cohorts.