Abrocitinib efficacy and safety in patients with moderate‐to‐severe atopic dermatitis: Results from phase 3 studies, including the long‐term extension JADE EXTEND study

Abstract

BackgroundAbrocitinib improved signs and symptoms of moderate‐to‐severe atopic dermatitis (AD) at 12 or 16 weeks in phase 3 studies with a manageable safety profile. Further understanding of the abrocitinib long‐term efficacy and safety profile is important for its appropriate use in treating chronic AD.ObjectiveTo evaluate the abrocitinib efficacy up to 48 weeks and long‐term safety in patients with moderate‐to‐severe AD.MethodsJADE EXTEND (NCT03422822) is an ongoing, phase 3, long‐term extension study that enrolled patients from previous abrocitinib AD trials. This analysis focusses on patients from the phase 3 JADE MONO‐1 (NCT03349060), JADE MONO‐2 (NCT03575871) and JADE COMPARE (NCT03720470) studies who completed the full treatment period of placebo or abrocitinib (200 mg or 100 mg once daily) and subsequently entered JADE EXTEND. Efficacy endpoints included the proportion of patients achieving skin clearance (Investigator's Global Assessment [IGA] 0/1 [clear/almost clear]; ≥75% improvement in Eczema Area and Severity Index [EASI‐75]) and itch response (Peak Pruritus Numerical Rating Scale [PP‐NRS] severity ≥4‐point improvement). Safety endpoints included treatment‐emergent adverse events (TEAEs), serious TEAEs and TEAEs leading to discontinuation. Data cut‐off: April 22, 2020.ResultsAs of the data cut‐off, ~70% and ~45% of patients received abrocitinib for ≥36 and ≥48 weeks, respectively. Nasopharyngitis, atopic dermatitis, nausea and upper respiratory tract infections were the most frequent TEAEs. Serious TEAEs occurred in 7% and 5% and TEAEs leading to study discontinuation occurred in 9% and 7% of patients receiving abrocitinib 200 mg and 100 mg, respectively. Week 48 efficacy responses with abrocitinib 200 mg and 100 mg were as follows: IGA 0/1 52% and 39%; EASI‐75 82% and 67%, and PP‐NRS severity ≥4‐point improvement 68% and 51%.ConclusionsIn patients with moderate‐to‐severe AD, long‐term abrocitinib treatment resulted in clinically meaningful skin and pruritus improvement. The long‐term safety profile was manageable and consistent with previous reports.

Short-Term Cardiovascular Complications in Dermatology Patients Receiving JAK-STAT Inhibitors

“…Given this, the results of this review can only be appropriately extrapolated to safety with short-term exposure of JAK-STATi when used for dermatological indications. Several integrated and open-label extension analyses are investigating the safety and efficacy of selected JAK-STATi, with follow-up up to 5 years . Median crude IR for MACE in these studies was 0.18 per 100 PEY, and 0.11 per 100 PEY for VTE.…”

“…Several integrated and open-label extension analyses are investigating the safety and efficacy of selected JAK-STATi, with follow-up up to 5 years. [59][60][61][62][63][64] Median crude IR for MACE in these studies was 0.18 per 100 PEY, and 0.11 per 100 PEY for VTE. Further studies involving placebo-controlled long-term extension to evaluate cardiovascular risk profiles are crucial to determine long-term safety of these medications.…”

The therapeutic effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on chemically induced atopic dermatitis

“…Abrocitinib attenuates in ammation by reducing cytokine production. A recent meta-analysis of several studies revealed that abrocitinib signi cantly improved the skin condition and itchiness of patients in an entire long-term e cacy (LTE) population treated for ≥ 36 and ≥ 48 weeks with abrocitinib 34 . However, some patients experienced adverse reactions, such as serious infections (herpes simplex, herpes zoster, and pneumonia), malignancy, thrombosis, and major adverse cardiovascular events 35 .…”

Effects of abrocitinib on pruritus and eczema symptoms and tolerance in patients with moderate‑to‑severe atopic dermatitis in randomized, double‑blind and placebo‑controlled trials: A systematic review and a meta‑analysis

“…By contrast, gastrointestinal dysfunction, nausea, dizziness and headache were the main symptoms in the 200 mg abrocitinib group. Reich et al ( 18 ) found that serious adverse reactions, such as inflammatory bowel disease, peritonsillitis, dehydration and asthma occurred after oral treatments with abrocitinib 200 mg, whereas one case of pneumonia was also found during follow-up. Serious adverse reactions, such as retinal detachment, acute pancreatitis, appendicitis, dizziness and epilepsy, were associated with 100 mg abrocitinib oral treatment ( 18 ), similar to the results of the present study.…”

“…Abrocitinib is a once-daily oral Janus kinase 1 (JAK1) inhibitor for long-term treatment of patients with moderate-to-severe AD ( 12 ) that rapidly relieves itching symptoms ( 13-17 ) and was first approved by the UK Medicines and Healthcare Products Regulatory Agency in September 2021. Due to good compliance, it was subsequently approved in Japan, South Korea, the European Union and the United States ( 18-20 ). On April 11, 2022, the China Food and Drug Administration approved abrocitinib for marketing in China for adult patients with refractory, moderate-to-severe AD who do not respond well to other systemic therapies, such as hormones or biological agents ( 21 , 22 ).…”