Efficacy and safety of abrocitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: a randomised, double-blind, multicentre phase 3 trial

Reich, Kristian; Thyssen, Jacob P.; Blauvelt, Andrew; Eyerich, Kilian; Soong, Weily; Rice, Zakiya P.; Hong, Hwanhee; Katoh, Norito; Valenzuela, Fernando; DiBonaventura, Marco; Bratt, Tamara A; Zhang, Fan; Clibborn, Claire; Rojo, Ricardo; Valdez, Hernán; Kerkmann, Urs

doi:10.1016/s0140-6736(22)01199-0

Cited by 115 publications

(89 citation statements)

References 14 publications

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“…Furthermore, abrocitinib demonstrated sustainable long-term efficacy through 52 weeks (118). The results of these trials are supporting the potential important role of JAK1 inhibition in patients who need fast relief of pruritus and skin inflammation in atopic dermatitis (113)(114)(115)(116)(117)(118)120).…”

Section: Abrocitinib (Pf-04965842)mentioning

confidence: 71%

JAK–STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review

Huang

Hung

et al. 2022

Front. Immunol.

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Atopic dermatitis (AD) is a chronic, inflammatory, pruritic form of dermatosis with heterogeneous manifestations that can substantially affect patients' quality of life. AD has a complex pathogenesis, making treatment challenging for dermatologists. The Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway plays a central role in modulating multiple immune axes involved in the immunopathogenesis of AD. In particular, Th2 cytokines, including interleukin (IL)-4, IL-5, IL-13, IL-31, and thymic stromal lymphopoietin, which contribute to the symptoms of chronic inflammation and pruritus in AD, are mediated by JAK–STAT signal transduction. Furthermore, JAK–STAT is involved in the regulation of the epidermal barrier and the modulation of peripheral nerves related to the transduction of pruritus. Targeting the JAK–STAT pathway may attenuate these signals and show clinical efficacy through the suppression of various immune pathways associated with AD. Topical and oral JAK inhibitors with variable selectivity have emerged as promising therapeutic options for AD. Notably, topical ruxolitinib, oral upadacitinib, and oral abrocitinib were approved by the U.S. Food and Drug Administration for treating patients with AD. Accordingly, the present study reviewed the role of JAK–STAT pathways in the pathogenesis of AD and explored updated applications of JAK inhibitors in treating AD.

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Section: Abrocitinib (Pf-04965842)mentioning

confidence: 71%

JAK–STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review

Huang

Hung

et al. 2022

Front. Immunol.

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“…The 200 mg (but not 100 mg) dose significantly reduced itch by week 2 compared with dupilumab [95]. Moreover, although significantly more patients achieved a 90% improvement in Eczema Area and Severity Index at week 4 and week 16 with abrocitinib compared with dupilumab, no differences were observed at week 26 [264]. In patients with AD aged 12 years and older (JADE MONO 1 and 2), abrocitinib showed rapid and significant improvements by week 12 compared with placebo.…”

Section: Jak Inhibitorsmentioning

confidence: 90%

Current and Emerging Strategies to Inhibit Type 2 Inflammation in Atopic Dermatitis

Haddad

Cyr

Arima

et al. 2022

Dermatol Ther (Heidelb)

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Type 2 immunity evolved to combat helminth infections by orchestrating a combined protective response of innate and adaptive immune cells and promotion of parasitic worm destruction or expulsion, wound repair, and barrier function. Aberrant type 2 immune responses are associated with allergic conditions characterized by chronic tissue inflammation, including atopic dermatitis (AD) and asthma. Signature cytokines of type 2 immunity include interleukin (IL)-4, IL-5, IL-9, IL-13, and IL-31, mainly secreted from immune cells, as well as IL-25, IL-33, and thymic stromal lymphopoietin, mainly secreted from tissue cells, particularly epithelial cells. IL-4 and IL-13 are key players mediating the prototypical type 2 response; IL-4 initiates and promotes differentiation and proliferation of naïve T-helper (Th) cells toward a Th2 cell phenotype, whereas IL-13 has a pleiotropic effect on type 2 inflammation, including, together with IL-4, decreased barrier function. Both cytokines are implicated in B-cell isotype class switching to generate immunoglobulin E, tissue fibrosis, and pruritus. IL-5, a key regulator of eosinophils, is responsible for eosinophil growth, differentiation, survival, and mobilization. In AD, IL-4, IL-13, and IL-31 are associated with sensory nerve sensitization and itch, leading to scratching that further exacerbates inflammation and barrier dysfunction. Various strategies have emerged to suppress type 2 inflammation, including biologics targeting cytokines or their receptors, and Janus kinase inhibitors that block intracellular cytokine signaling pathways. Here we review type 2 inflammation, its role in inflammatory diseases, and current and future therapies targeting type 2 pathways, with a focus on AD. Infographic Supplementary Information The online version contains supplementary material available at 10.1007/s13555-022-00737-7.

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“…21 JADE COMPARE and JADE DARE established the superiority of abrocitinib 200 mg over dupilumab 300 mg, every other week, in rapidly reducing pruritus at 2 weeks as assessed by PP-NRS. 22,24 In JADE DARE, abrocitinib 200 mg was superior to dupilumab 300 mg, every other week, in reducing disease severity at both primary and secondary endpoints, as assessed by EASI-90 at weeks 4 and 16. 24 Lastly, in JADE TEEN abrocitinib 100 and 200 mg were more efficacious than placebo in reducing disease severity, for all primary endpoints, over 12 weeks of therapy.…”

Section: Discussionmentioning

confidence: 99%

“…22,24 In JADE DARE, a greater proportion of patients achieved an EASI 90 response after taking abrocitinib 200 mg for 16 weeks compared with those taking dupilumab (54.3% vs 41.9%, respectively, P < 0.001). 24 Not only is abrocitinib potentially more effective than dupilumab, some patients may not respond to biologics, and others may prefer oral medications over injectables. 26 However, the paradox of a 16-week trial for head-to-head comparison of abrocitinib to dupilumab for patients with moderate-to-severe AD, is the chronicity of disease.…”

Section: Relevance To Patient Care and Clinical Practicementioning

confidence: 99%

Abrocitinib: A New FDA-Approved Drug for Moderate-to-Severe Atopic Dermatitis

2022

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Objective The objective of this article is to review abrocitinib, an oral Janus kinase (JAK) 1 inhibitor, for the treatment of patients with moderate-to-severe atopic dermatitis (AD). Data Sources A literature search of MEDLINE (PubMed) was performed for articles from inception through end-March 2022 using the following search terms: atopic dermatitis, abrocitinib, PF-04965842, methotrexate, cyclosporine, dupilumab, ruxolitinib, and JAK-STAT pathway. Study Selection and Data Extraction English articles relating to pharmacology, pharmacokinetics, efficacy, and safety of abrocitinib, and other conventional systemic medications for AD, were included. Data Synthesis Across phase IIb and phase III clinical trials, abrocitinib was efficacious with an average of 47.5% patients on 200 mg abrocitinib and 32.0% on 100 mg abrocitinib achieving an Investigator’s Global Assessment (IGA) of 0 or 1 at 12 weeks. In comparison with dupilumab 300 mg subcutaneously every other week, patients on abrocitinib 200 mg once daily had improved disease severity and itch response. The majority of adverse events were not severe and self-limited. Relevance to Patient Care and Clinical Practice Prior to Food and Drug Administration (FDA) approval of abrocitinib, prednisone was the only FDA-approved oral medication for AD. Although biologics such as dupilumab have revolutionized care, some patients prefer oral medications. Compared with clinical trials of conventional AD treatments, abrocitinib appears more effective. Conclusions Abrocitinib is an efficacious oral JAK 1 inhibitor recently FDA-approved for patients ≥ 18 years old with moderate-to-severe AD who have not responded to systemic medications or when contraindicated otherwise.

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Efficacy and safety of abrocitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: a randomised, double-blind, multicentre phase 3 trial

Cited by 115 publications

References 14 publications

JAK–STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review

JAK–STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review

Current and Emerging Strategies to Inhibit Type 2 Inflammation in Atopic Dermatitis

Abrocitinib: A New FDA-Approved Drug for Moderate-to-Severe Atopic Dermatitis

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