Magnitude and Time Course of Response to Abrocitinib for Moderate-to-Severe Atopic Dermatitis

Reich, Kristian; Lio, Peter; Bissonnette, Robert; Alexis, Andrew F.; Lebwohl, Mark; Pink, Andrew; Kabashima, Kenji; Boguniewicz, Mark; Nowicki, Roman; Valdez, Hernán; Zhang, Fan; DiBonaventura, Marco; Cameron, Michael C.; Clibborn, Claire

doi:10.1016/j.jaip.2022.08.042

Cited by 8 publications

(9 citation statements)

References 23 publications

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“…Abrocitinib decreases pruritus very rapidly and effectively, and itch relief was considered the most important factor in determining treatment response by AD patients [ 48 ]. Moreover, improvements in pruritus contribute to better sleep and further increase the quality of life in these patients [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of JAK1 Inhibitor Abrocitinib in Atopic Dermatitis

et al. 2023

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Abrocitinib is a JAK1 selective inhibitor recently approved for the treatment of moderate-to-severe atopic dermatitis in adults. It has demonstrated efficacy and safety in several clinical trials, both in children and adults, in monotherapy, and compared with dupilumab. The expected EASI-75 response rate estimates at week 12 are 62.9% (95% CrI 42.5–79.9%) for abrocitinib 200 mg and 43.0% (95% CrI 24.8–64.0%) for abrocitinib 100 mg. Abrocitinib has shown a faster effect than dupilumab as regards early alleviation of itch. Because of the incomplete target selectivity of JAK inhibitors, when abrocitinib treatment is considered, laboratory screening is necessary, latent tuberculosis must be screened for, active infections are a contraindication, and special caution must be exerted in treating elderly patients and those predisposed to thromboembolic events. Even though recent meta-analyses of clinical trials have not shown that atopic dermatitis, or its treatment with JAK inhibitors or dupilumab, modify the risk of deep venous thrombosis or pulmonary embolism, long-term follow-up studies will better define the safety profile of abrocitinib.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of JAK1 Inhibitor Abrocitinib in Atopic Dermatitis

et al. 2023

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“…30 Abrocitinib showed high short-term efficacy in moderate-to-severe AD in adults and adolescents with better responses of objective severity and subjective symptoms such as pruritus, sleep, QoL for 200 than 100 mg (EASI-75 under monotherapy in adults 61%-63% for 200 mg, 40%-45% for 100 mg (Week 12 (W12)); plus topicals 60%-71% (W16); in adolescents 69%-72%. 30,37,39,45,55,66,94,[106][107][108] Early itch relief by Week 2 of abrocitinib was associated with a higher probability of (almost) clear skin at W12. 95,96 The majority of responders at W12 maintained their response to both doses at W48 of cumulative treatment (EASI-75: 79% (100 mg) -87% (200 mg)).…”

Section: Ind I C Ati On S Long -Term Safe T Y and Effi C Ac Y Of Jak Imentioning

confidence: 99%

“…Tralokinumab inhibits binding to both IL‐13Rα1 and the IL‐13Rα2 decoy receptor thought to be involved in endogeneous regulation of IL‐13 7,30,93 . Lebrikizumab selectively prevents the formation of the IL‐13Rα1/IL‐4Rα receptor signalling complex 20,94–96 but allows the binding of IL‐13 to 13Rα2. In the Phase III trials, lebrikizumab 250 mg Q2W compared to placebo showed superior efficacy in adolescents and adults with moderate‐to‐severe AD at Week 16 both as a monotherapy (EASI‐75: 58.8%/52.1% vs.16.2%/18.1%) 90 and in combination with TCS (EASI‐74: 69.5% vs. 42.2%) 89 with significant improvements of pruritus and QoL 89,90 .…”

Section: Lebrikizumab: Recent Approval In Adolescents and Adults With...mentioning

confidence: 99%

“…Abrocitinib is approved for AD in adults, in the United Kingdom also for adolescents 30 . Abrocitinib showed high short‐term efficacy in moderate‐to‐severe AD in adults and adolescents with better responses of objective severity and subjective symptoms such as pruritus, sleep, QoL for 200 than 100 mg (EASI‐75 under monotherapy in adults 61%–63% for 200 mg, 40%–45% for 100 mg (Week 12 (W12)); plus topicals 60%–71% (W16); in adolescents 69%–72% 30,37,39,45,55,66,94,106–108 . Early itch relief by Week 2 of abrocitinib was associated with a higher probability of (almost) clear skin at W12 95,96 .…”

Section: Indications Long‐term Safety and Efficacy Of Jakimentioning

confidence: 99%

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Treatment of atopic dermatitis: Recently approved drugs and advanced clinical development programs

Müller,

Maintz,

Bieber

2024

Allergy

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Atopic dermatitis (AD) represents the most common skin disease characterized by heterogeneous endophenotypes and a high disease burden. In Europe, six new systemic therapies for AD have been approved: the biologics dupilumab (anti‐interleukin‐4 receptor (IL‐4R) α in 2017), tralokinumab (anti‐IL‐13 in 2021), lebrikizumab (anti‐IL‐13 in 2023), and the oral janus kinase (JAK) inhibitors (JAKi) targeting JAK1/2 (baricitinib in 2020 in the EU) or JAK1 (upadacitinib in 2021 and abrocitinib in 2022). Herein, we give an update on new approvals, long‐term safety, and efficacy. Upadacitinib and abrocitinib have the highest short‐term efficacy among the approved systemic therapies. In responders, dupilumab and tralokinumab catch up regarding long‐term efficacy and incremental clinical benefit within continuous use. Recently, the European Medicines Agency has released recommendations for the use of JAKi in patients at risk (cardiovascular and thromboembolic diseases, malignancies, (former) smoking, and age ≥65 years). Furthermore, we give an overview on emerging therapies currently in Phase III trials. Among the topical therapies, tapinarof (aryl hydrocarbon receptor), ruxolitinib (JAK1/2i), delgocitinib (pan‐JAKi), asivatrep (anti‐transient receptor potential vanilloid), and phosphodiesterase‐4‐inhibitors (roflumilast, difamilast) are discussed. Among systemic therapies, current data on cord‐blood‐derived mesenchymal stem cells, CM310 (anti IL‐4Rα), nemolizumab (anti‐IL‐31RA), anti‐OX40/OX40L‐antibodies, neurokinin‐receptor‐1‐antagonists, and difelikefalin (κ‐opioid‐R) are reported.

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“… 531 Abrocitinib has manageable safety, and its common adverse events include nausea, headache, acne and reduced platelet counts. 532 , 533 Therefore, its benefit-to-harm ratio needs to be thoroughly investigated before it can be used for the long-term treatment of AD. Strikingly, deucravacitinib (BMS-986165), by producing a distinctively allosteric mechanism to combine with the TYK2 regulatory domain and not influence the functions of JAK1/2/3, became the first oral agent that was used to treat psoriasis with a favorable safety profile.…”

Section: Jak-stat Pathway and Treatmentmentioning

confidence: 99%

Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

Xue

Yao

et al. 2023

Sig Transduct Target Ther

129

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The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism of transmembrane signal transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, and other specific molecules activate JAK-STAT signaling to drive a series of physiological and pathological processes, including proliferation, metabolism, immune response, inflammation, and malignancy. Dysregulated JAK-STAT signaling and related genetic mutations are strongly associated with immune activation and cancer progression. Insights into the structures and functions of the JAK-STAT pathway have led to the development and approval of diverse drugs for the clinical treatment of diseases. Currently, drugs have been developed to mainly target the JAK-STAT pathway and are commonly divided into three subtypes: cytokine or receptor antibodies, JAK inhibitors, and STAT inhibitors. And novel agents also continue to be developed and tested in preclinical and clinical studies. The effectiveness and safety of each kind of drug also warrant further scientific trials before put into being clinical applications. Here, we review the current understanding of the fundamental composition and function of the JAK-STAT signaling pathway. We also discuss advancements in the understanding of JAK-STAT–related pathogenic mechanisms; targeted JAK-STAT therapies for various diseases, especially immune disorders, and cancers; newly developed JAK inhibitors; and current challenges and directions in the field.

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Magnitude and Time Course of Response to Abrocitinib for Moderate-to-Severe Atopic Dermatitis

Cited by 8 publications

References 23 publications

Efficacy and Safety of JAK1 Inhibitor Abrocitinib in Atopic Dermatitis

Efficacy and Safety of JAK1 Inhibitor Abrocitinib in Atopic Dermatitis

Treatment of atopic dermatitis: Recently approved drugs and advanced clinical development programs

Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

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