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Abrocitinib holds promise for moderate-to-severe AD

Audrey Abella
30 Sep 2020

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.

 

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Most Read Articles
07 Aug 2020
Concomitant treatment with a nonsteroidal anti-inflammatory drug (NSAID) following myocardial infarction (MI) is associated with a higher risk of cardiovascular and bleeding events, a study has shown.
Roshini Claire Anthony, 06 Oct 2020

Several strategies have been proposed to help manage the adverse events (AEs) that emerged during the BEACON CRC trial which assessed the effect of encorafenib plus cetuximab in patients with BRAF V600E mutant metastatic colorectal cancer (mCRC) who had progressed after one or two prior regimens.