Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials

The Lancet, Journal Year: 2022, Volume and Issue: 399(10341), P. 2113 - 2128

Published: May 26, 2022

Language: Английский

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Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis

JAMA Dermatology, Journal Year: 2021, Volume and Issue: 157(9), P. 1047 - 1047

Published: Aug. 4, 2021

Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease with an unmet need for treatments that provide rapid and high levels of clearance itch improvement.

Language: Английский

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Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial

The Lancet, Journal Year: 2021, Volume and Issue: 397(10290), P. 2169 - 2181

Published: May 21, 2021

Language: Английский

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European guideline (EuroGuiDerm) on atopic eczema: part I – systemic therapy

Journal of the European Academy of Dermatology and Venereology, Journal Year: 2022, Volume and Issue: 36(9), P. 1409 - 1431

Published: Aug. 18, 2022

Abstract The evidence‐ and consensus‐based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline Consensus Statement Development Manual. Four consensus conferences were held between December 2020 July 2021. Twenty‐nine experts (including clinicians patient representatives) from 12 European countries participated. This first part of includes general information its scope purpose, health questions covered, target users a methods section. It also provides guidance which patients should be treated systemic therapies, as well recommendations detailed each drug. treatment options discussed comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab tralokinumab) janus kinase inhibitors (abrocitinib, baricitinib upadacitinib). Part two will address avoidance provocation factors, dietary interventions, immunotherapy, complementary medicine, educational occupational psychodermatological aspects, perspective considerations for paediatric, adolescent, pregnant breastfeeding patients.

Language: Английский

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JAK inhibitors in the treatment of atopic dermatitis

Journal of Allergy and Clinical Immunology, Journal Year: 2021, Volume and Issue: 148(4), P. 927 - 940

Published: Aug. 24, 2021

Language: Английский

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

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 19, 2023

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

Language: Английский

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European guideline (EuroGuiDerm) on atopic eczema – part II: non‐systemic treatments and treatment recommendations for special AE patient populations

Journal of the European Academy of Dermatology and Venereology, Journal Year: 2022, Volume and Issue: 36(11), P. 1904 - 1926

Published: Sept. 3, 2022

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline Consensus Statement Development Manual. Four consensus conferences were held between December 2020 July 2021. Twenty-nine experts (including clinicians patient representatives) from 12 European countries participated. This second part of includes recommendations detailed information basic therapy emollients moisturizers, topical anti-inflammatory treatment, antimicrobial antipruritic treatment UV phototherapy. Furthermore, this covers techniques for avoiding provocation factors, as well dietary interventions, immunotherapy, complementary medicine educational interventions patients deals occupational psychodermatological aspects disease. It also contains guidance paediatric adolescent pregnant or breastfeeding women, considerations who want to have a child. A chapter perspective is provided. first guideline, published separately, systemic conventional immunosuppressive drugs, biologics janus kinase (JAK) inhibitors, scope purpose section methodology.

Language: Английский

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Efficacy and Safety of Upadacitinib in Patients With Moderate to Severe Atopic Dermatitis

JAMA Dermatology, Journal Year: 2022, Volume and Issue: 158(4), P. 404 - 404

Published: March 9, 2022

Primary results from the Measure Up 1 and 2 studies demonstrated upadacitinib efficacy safety through 16 weeks in patients with atopic dermatitis. Longer-term outcomes remain unknown.To evaluate long-term (52 weeks) of treatment dermatitis.Measure are ongoing double-blind, placebo-controlled, replicate phase 3 randomized clinical trials that include adults adolescents moderate to severe dermatitis at 151 154 centers, respectively. Cutoffs for this analysis were December 21, 2020 (Measure 1), January 15, 2021 2).Patients 1:1:1 receive once-daily oral 15 mg, 30 or placebo. At week 16, baseline mg (273 260 2, respectively) (270 268 patients) continued assigned treatment; placebo-treated rerandomized 1:1 (121 120 (123 121 a double-blinded manner.Safety efficacy, including 75% improvement Eczema Area Severity Index Validated Investigator Global Assessment Atopic Dermatitis score clear (0) almost (1) greater grades improvement, assessed.Measure included total 1609 (mean [SD] age, 33.8 [15.6] years; 727 women [45.2%]; 882 men [54.8%]). Efficacy was maintained 52. 52, achieved by 82.0% (95% CI, 77.0%-86.9%) 79.1% 73.9%-84.4%) continuing 15-mg dose 84.9% 80.3%-89.5%) 84.3% 79.6%-89.0%) 30-mg (for respectively); 59.2% 52.9%-65.5%) 52.6% 46.2%-59.1%) 62.5% 56.3%-68.7%) 65.1% 58.9%-71.2%) studies, Treatment discontinuation due adverse events low overall but slightly higher dose. Both doses well tolerated no new signals.In follow-up data trials, longer-term favorable benefit-risk profile, sustained responses 52 weeks.ClinicalTrials.gov Identifiers: NCT03569293 1) NCT03607422 2).

Language: Английский

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

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 8, 2022

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

Language: Английский

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Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis

RMD Open, Journal Year: 2023, Volume and Issue: 9(1), P. e002735 - e002735

Published: Feb. 1, 2023

To evaluate the long-term safety profile for upadacitinib across rheumatoid arthritis (RA), psoriatic (PsA), ankylosing spondylitis (AS) and atopic dermatitis (AD).Safety data from clinical trials of 15 mg 30 (AD only) treating RA, PsA, AS AD as June 2021 were analysed; some RA PsA studies included adalimumab methotrexate active comparators. Treatment-emergent adverse events (TEAEs) presented by disease exposure-adjusted event rates per 100 patient years (E/100 PY).The analysis 6991 patients (RA, n=3209; n=907; AS, n=182; AD, n=2693) who received at least one dose upadacitinib, representing 425 PY exposure (maximum duration 2.75-5.45 years) diseases. Rates PY) any TEAE (205.5-278.1) leading to discontinuation (4.5-5.4) similar diseases; serious TEAEs numerically higher in with PsA. herpes zoster (1.6-3.6), non-melanoma skin cancer (0-0.8) elevations creatine phosphokinase levels (4.4-7.9) than comparators populations. Deaths (0-0.8), infections (0-3.9), major cardiovascular (0-0.4), venous thromboembolism (<0.1-0.4) malignancies (0.3-1.4) observed, generally lowest AD. Increased acne observed only.Findings this demonstrate that is well tolerated differences profiles likely reflective varying characteristics populations.NCT02675426, NCT02706951, NCT02706847, NCT02629159, NCT02706873, NCT03086343, NCT03104374, NCT03104400, NCT03178487, NCT03569293, NCT03568318 NCT03607422.

Language: Английский

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