Abrocitinib holds promise for moderate-to-severe AD

The investigational JAK1* selective inhibitor abrocitinib was effective and well-tolerated in adolescents and adults with moderate-to-severe atopic dermatitis (AD), the phase III JADE MONO-2 trial has shown.

AD affects children, adolescents, and adults, and greatly impairs quality of life (QoL). [Ann Allergy Asthma Immunol 2018;121:340-347; J Am Acad Dermatol 2018;79:448-456.e30] Patients who fail to respond to topical remedies are usually managed with systemic therapy; however, adverse events (AEs) often confound long-term use. [J Eur Acad Dermatol Venereol 2018;32:850-878]

Moreover, the use of the approved AD drug dupilumab is limited by inadequate response, patients’ intolerability to injections, and AEs. [Br J Dermatol 2019;181:459-473; Biologics 2019;13:79-82] “Hence, additional treatments … are needed,” said the researchers.

The team randomized 391 participants (mean age 35 years, 59 percent male) 2:2:1 to receive oral abrocitinib 100 or 200 mg QD or placebo for 12 weeks. [JAMA Dermatol 2020;156:863-873]

At week 12, significantly more abrocitinib 100- and 200-mg vs placebo recipients achieved IGA** (28 percent and 38 percent vs 9 percent), EASI-75*** (44 percent and 61 percent vs 10 percent), and PP-NRS^# responses (45 percent and 55 percent vs 12 percent; p<0.001 for all).

Well-tolerated, better QoL

Despite the high treatment-emergent adverse event (TEAE) rates with abrocitinib 100 and 200 mg (n=99 and 102), discontinuation rates due to AEs were low (n=6 and 5), as were serious infection (n=3 and 0) and serious AE rates (n=5 and 2). Eczema herpeticum/Kaposi varicelliform eruption TEAEs were observed with abrocitinib 100 mg (n=2). Herpes zoster TEAEs occurred with abrocitinib 200 mg (n=2), which resolved even without treatment.

Week 12 saw greater improvements in DLQI^## (−8.3 and −9.8 vs −3.9) and Children’s DLQI scores (−4.8 and −9.7 vs −2.7) with abrocitinib 100 and 200 mg vs placebo.

Both abrocitinib 100 and 200 mg also yielded greater reductions in PSAAD^### vs placebo (−2.4 and −3.0 vs −0.8), which as per the researchers, could explain the substantial QoL benefits observed. “Abrocitinib may mediate this effect through various mechanisms, including relief of inflammation and/or direct inhibition of neuronal JAK1 signalling of pruritogenic cytokines.”

Confirming JADE MONO-1

The results validate the findings of the JADE MONO-1 trial. [Lancet 2020;396:255-266] “[Both studies showed that] IGA and EASI-75 responses were observed [with abrocitinib] as early as week 2 of treatment and were sustained until week 12,” said the researchers.

Also, the current trial included more Asian patients than JADE MONO-1 (33 percent vs 15 percent), who apparently have different subsets of helper T cell-driven inflammatory activity vs patients of European descent. [J Allergy Clin Immunol 2015;136:1254-1264] “[As such,] both trials support the efficacy and safety profile of abrocitinib in a broad range of patients, possibly related to the inhibition of a range of AD-associated cytokines,” they added.

Larger and longer trials are warranted to determine the long-term efficacy and safety of abrocitinib, as “more patients [may achieve] IGA and/or EASI-75 responses with longer treatment,” they said. Future trials should also take into account subsets of patients that were not well-represented in the current trial (eg, adolescents, non-whites) to ascertain generalizability of the findings. The potential of abrocitinib in combination therapy should also be explored in future studies.