Data support abrocitinib use beyond 2 years in adolescents with AD

Treating adolescents with moderate-to-severe atopic dermatitis (AD) with the Janus kinase 1-selective inhibitor abrocitinib has demonstrated an acceptable long-term safety profile and maintained efficacy for up to 112 weeks, as shown in an adolescent-focused post hoc analysis of five phase III trials.

As for treatment-emergent adverse events (TEAEs) of special interest, no deaths or adjudicated events of malignancies were reported. There were incidents of serious infections and herpes zoster (HZ) infections. However, few adjudicated opportunistic HZ infections were noted (three patients on abrocitinib 200 mg and one on 100 mg).

The risk of thrombotic vascular events was also monitored as TEAEs of special interest, with a single pulmonary embolism (PE) event occurring in an adolescent receiving abrocitinib 200 mg who had a family history of PE and one nonserious major adverse cardiovascular event in an adolescent receiving the 100-mg dose. [EADV 2024, abstract 2323]

"This analysis of adolescents with moderate-to-severe AD treated for up to 4.6 years supports the acceptable long-term safety profile of abrocitinib, with no new safety signals observed," said Professor Amy Paller, a paediatric dermatologist at the Northwestern University Feinberg School of Medicine in Chicago, Illinois, US.

The efficacy of both doses of abrocitinib, measured by response rates of 75 percent or 100 percent improvement on the Eczema Area and Severity Index (EASI-75/-100), an Investigator’s Global Assessment (IGA) score of 0 or 1 with a ≥2-point improvement, among other metrics, was maintained for >2 years.

Safety results: median exposure of 2.4 years

Patients aged 12 to <18 years who received ≥1 dose of abrocitinib while participating in JADE MONO-1, MONO-2, TEEN, REGIMEN, and/or their extension, JADE EXTEND, were pooled in this integrated analysis. [Lancet 2020;396:255-266; JAMA Dermatol 2020;156:863-873; JAMA Dermatol 2021;157:1165-1173; J Am Acad Dermatol 2022;86:104-112; J Eur Acad Dermatol Venereol 2023;37:2056-2066] Only those who maintained the same abrocitinib dose throughout the entire exposure period were included in the safety analysis.

The median duration of abrocitinib exposure was 882 days for the 200-mg dose (n=289) and 863 days for the 100-mg dose (n=201).

Serious TEAEs were reported at a numerically higher incidence rate (IR) with the 200-mg dose vs the 100-mg dose (5.47 vs 3.45 patients with events per 100 patient-years [PY]), as were TEAEs leading to abrocitinib discontinuation (6.78 vs 5.39 per 100 PY). However, the IRs of severe TEAEs were similar (4.67 vs 4.98 per 100 PY).

The only TEAE of special interest with an IR >1 for both doses was "all HZ infections" (2.17 vs 1.47 per 100 PY).

“So far, we haven't seen any of the longer-term side effects we're concerned about. However, there are some AEs we need to be on the lookout for, particularly HZ,” concluded Paller.

Efficacy results: median exposure of ≥2.5 years

Only adolescents who were randomly assigned to abrocitinib and subsequently enrolled in JADE EXTEND were included in the efficacy analysis. The median duration of exposure was 971 days for abrocitinib 200 mg (n=170) and 899 days for the 100-mg dose (n=187).

At 112 weeks, the EASI-75 response rates for abrocitinib 200 mg and 100 mg were 84.8 percent and 83.3 percent, respectively, with the corresponding IGA 0/1 rates of 57.1 percent for both.

Notably, the proportion of adolescents achieving the more stringent EASI-100 response at 112 weeks was numerically higher with the higher dose of abrocitinib (30.3 percent vs 18.9 percent).