Ulcerative colitis

The Lancet, Journal Year: 2023, Volume and Issue: 402(10401), P. 571 - 584

Published: Aug. 1, 2023

Language: Английский

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Ulcerative Colitis in Adults

JAMA, Journal Year: 2023, Volume and Issue: 330(10), P. 951 - 951

Published: Sept. 12, 2023

Importance Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, with prevalence exceeding 400 per 100 000 in North America. Individuals UC have lower life expectancy and are at increased risk for colectomy colorectal cancer. Observations impairs quality secondary to inflammation colon causing diarrhea rectal bleeding. Extraintestinal manifestations, such as primary sclerosing cholangitis, occur approximately 27% patients UC. People require monitoring symptoms biomarkers (eg, fecal calprotectin), colonoscopy 8 years from diagnosis surveillance dysplasia. Risk stratification by disease location Montreal Classification) activity Mayo Score) can guide management First-line therapy induction maintenance remission mild moderate 5-aminosalicylic acid. Moderate severe may oral corticosteroids bridge medications that sustain (biologic monoclonal antibodies against tumor necrosis factor [eg, infliximab], α4β7 integrins [vedolizumab], interleukin [IL] 12 IL-23 [ustekinumab]) small molecules inhibit janus kinase tofacitinib) or modulate sphingosine-1-phosphate (ozanimod). Despite advances medical therapies, highest response these treatments ranges 30% 60% clinical trials. Within 5 diagnosis, 20% hospitalized 7% undergo colectomy. The cancer after 20 duration 4.5%, people 1.7-fold higher compared general population. Life 80.5 females 76.7 males, which shorter than without Conclusions Relevance affects every An effective treatment acid, whereas be treated advanced therapies target specific pathways, including factor, integrins, IL-12 cytokines, well molecule targeting sphingosine-1-phosphate.

Language: Английский

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Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease

New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 388(21), P. 1966 - 1980

Published: May 24, 2023

Upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is under investigation for the treatment of Crohn's disease. Download a PDF Research Summary. In two phase 3 induction trials (U-EXCEL and U-EXCEED), we randomly assigned patients with moderate-to-severe disease to receive 45 mg upadacitinib or placebo (2:1 ratio) once daily 12 weeks. Patients who had clinical response therapy were in U-ENDURE maintenance trial 15 upadacitinib, 30 (1:1:1 52 The primary end points (week 12) 52) remission (defined as Disease Activity Index score <150 [range, 0 600, higher scores indicating more severe activity]) endoscopic decrease Simple Endoscopic Score [SES-CD; range, 56, disease] >50% from baseline [or SES-CD 4 at baseline, ≥2 baseline]). A total 526 underwent randomization U-EXCEL, 495 U-EXCEED, 502 U-ENDURE. significantly percentage received 45-mg than those (in 49.5% vs. 29.1%; 38.9% 21.1%) 45.5% 13.1%; 34.6% 3.5%) (P<0.001 all comparisons). At week U-ENDURE, 15-mg (37.3%) 30-mg (47.6%) (15.1%), (27.6%) (40.1%) (7.3%) Herpes zoster infections occurred frequently groups respective groups, hepatic disorders neutropenia frequent group other groups. Gastrointestinal perforations developed 1 patient each upadacitinib. Upadacitinib was superior (Funded by AbbVie; ClinicalTrials.gov numbers, NCT03345849, NCT03345836, NCT03345823.) QUICK TAKE VIDEO SUMMARYUpadacitinib 02:52

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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Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies

The Lancet, Journal Year: 2023, Volume and Issue: 401(10383), P. 1159 - 1171

Published: March 2, 2023

Etrasimod, a once-daily, oral, sphingosine 1-phosphate (S1P) receptor modulator that selectively activates S1P subtypes 1, 4, and 5, with no detectable activity on S1P2,3, is in development for the treatment of immune-mediated diseases, including ulcerative colitis. In these two phase 3 trials, we aimed to evaluate safety efficacy etrasimod adult patients moderately severely active colitis.In independent randomised, multicentre, double-blind, placebo-controlled, ELEVATE UC 52 12, adults moderate-to-severe colitis an inadequate or loss response intolerance at least one approved therapy were randomly assigned (2:1) once-daily oral 2 mg placebo. Patients enrolled from 315 centres 40 countries. 12 407 37 Randomisation was stratified by previous exposure biologicals Janus kinase inhibitor (yes vs no), baseline corticosteroid use disease (modified Mayo score [MMS]; 4-6 7-9). comprised 12-week induction period followed 40-week maintenance treat-through design. independently assessed week 12. The primary endpoints proportion clinical remission weeks Safety evaluated both trials. registered ClinicalTrials.gov, NCT03945188 NCT03996369, respectively.Patients between June 13, 2019, Jan 28, 2021. Sept 15, 2020, Aug screened 821 606 patients, respectively, 433 354 subsequently undergoing random assignment. full analysis set 289 144 238 116 52, significantly greater group achieved compared placebo completion (74 [27%] 274 ten [7%] 135 patients; p<0·0001) (88 [32%] nine p<0·0001). 55 (25%) 222 had 17 (15%) 112 end (p=0·026). Adverse events reported 206 (71%) 81 (56%) (47%) 54 No deaths malignancies reported.Etrasimod effective well tolerated as Etrasimod option unique combination attributes might address persistent unmet needs colitis.Arena Pharmaceuticals.

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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Strategies for targeting cytokines in inflammatory bowel disease

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(8), P. 559 - 576

Published: March 14, 2024

Language: Английский

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EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update

Annals of the Rheumatic Diseases, Journal Year: 2024, Volume and Issue: 83(6), P. 706 - 719

Published: March 18, 2024

New modes of action and more data on the efficacy safety existing drugs in psoriatic arthritis (PsA) required an update EULAR 2019 recommendations for pharmacological treatment PsA.

Language: Английский

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Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn’s Disease: Prospective Real-World Experience

Clinical Gastroenterology and Hepatology, Journal Year: 2023, Volume and Issue: 21(7), P. 1913 - 1923.e2

Published: March 8, 2023

Language: Английский

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Improving IBD outcomes in the era of many treatment options

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(2), P. 79 - 80

Published: Jan. 12, 2023

Language: Английский

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