Abrocitinib effectively controls AD regardless of dosing regimen
In patients with moderate-to-severe atopic dermatitis (AD), flexible dosing of abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, appeared as beneficial as the continuous high-dose regimen. This was demonstrated in a post hoc analysis of two studies from the JADE* clinical development programme.
In the phase III JADE REGIMEN study, abrocitinib demonstrated efficacy in maintaining response to treatment and recapturing responses following a flare in patients with moderate-to-severe atopic dermatitis. [J Am Acad Dermatol 2022;86:104-112] However, the long-term efficacy of flexible (ie, variable) dosing has yet to be analysed.
“We wanted to evaluate the long-term efficacy of flexible abrocitinib treatment with step-up and step-down approaches on multiple occasions,” said Dr Erman Güler from Pfizer Inc, Istanbul, Turkey, who presented the findings at WCD 2023.
“We found a higher proportion of responders with continuous treatment with abrocitinib 200 mg once daily, but flexible dosing also resulted in clinically meaningful and sustained improvements to itch and skin signs in a substantial proportion of patients with moderate-to-severe AD,” Güler said.
The team pooled data from JADE REGIMEN and JADE EXTEND. Response to abrocitinib treatment was analysed in two populations: the flexible and continuous dosing cohorts. [WCD 2023, session FC18]
The flexible dosing group included 90 participants who have responded to induction abrocitinib 200 mg for 12 weeks, stepped down to 100 mg during the 40-week maintenance phase, stepped up again to 200 mg + topical corticosteroids (TCS) for 12 weeks after experiencing a flare (JADE REGIMEN), and then down again to 100 mg ± TCS (JADE EXTEND). Considering the flaring at the initial step-down, Güler said their disease may be a bit more aggressive, or that they may be more prone to flares.
The continuous dosing group comprised patients randomized to abrocitinib 200 mg or placebo from qualifying JADE studies (MONO-1 and -2, TEEN, COMPARE, and DARE) and those who were allocated to abrocitinib 200 mg ± TCS in JADE EXTEND. Of note, placebo recipients in the qualifying trials only received their first abrocitinib dose in JADE EXTEND.
Skin clearance, itch responses
The starting point was lower for the continuous dosing group, yet it caught up with the flexible dosing group by week 4. From week 12 onwards, the curves began to diverge, with higher rates in the continuous (>90 percent [EASI-50**] and >80 percent [EASI-75**]) vs the variable dosing group by week 48 (>80 percent and >70 percent, respectively). Nonetheless, these reflect substantial proportions of participants achieving favourable skin clearance responses with both dosing regimens, noted Güler.
In the flexible dosing group, barring the occasional dips in the curves, treatment effect was relatively stable over time. “This means that although participants flared during the initial step-down, majority of the responses were maintained with no apparent loss of efficacy over the long term,” Güler explained.
PP-NRS4*** response rates at week 48 were higher with continuous vs flexible dosing (67 percent vs 44 percent). Nonetheless, similar to the skin clearance responses, itch response was sustained for both dosing regimens.
Individualized treatment warranted
AD has a relapsing-remitting course with a heterogeneous nature that requires individualized and flexible treatment. [Lancet 2020;396:345-360] “The current findings suggest that both continuous and flexible dosing were efficacious in the long-term,” Güler concluded.