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Caballero-Mateos AM, Cañadas-de la Fuente GA. Game changer: How Janus kinase inhibitors are reshaping the landscape of ulcerative colitis management. World J Gastroenterol 2024; 30:3942-3953. [PMID: 39351053 PMCID: PMC11438661 DOI: 10.3748/wjg.v30.i35.3942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 08/19/2024] [Accepted: 08/22/2024] [Indexed: 09/13/2024] Open
Abstract
Recent advancements in the treatment landscape of ulcerative colitis (UC) have ushered in a new era of possibilities, particularly with the introduction of Janus kinase (JAK)-signal transducer and activator of transcription inhibitors. These novel agents offer a paradigm shift in UC management by targeting key signaling pathways involved in inflammatory processes. With approved JAK inhibitors (JAKis), such as tofacitinib, filgotinib, and upadacitinib, clinicians now have powerful tools to modulate immune responses and gene expression, potentially revolutionizing the treatment algorithm for UC. Clinical trials have demonstrated the efficacy of JAKis in inducing and maintaining remission, presenting viable options for patients who have failed conventional therapies. Real-world data support the use of JAKis not only as first-line treatments but also in subsequent lines of therapy, particularly in patients with aggressive disease phenotypes or refractory to biologic agents. The rapid onset of action and potency of JAKis have broadened the possibilities in the management strategies of UC, offering timely relief for patients with active disease and facilitating personalized treatment approaches. Despite safety concerns, including cardiovascular risks and infections, ongoing research and post-marketing surveillance will continue to refine our understanding of the risk-benefit profile of JAKis in UC management.
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Carvalhas Gabrielli AM, Ferretti F, Monico CM, Tombetti E, Maconi G, Romeo S, Piazza O Sed N, Caprioli F, Mazzola AM, Alicante S, Bertè R, Lolli E, Scribano ML, Buscarini E, Ricci C, Carmagnola S, Ardizzone S, Cannatelli R. Effect of Tofacitinib on One-Year Colectomy Risk in Anti-TNF Refractory Ulcerative Colitis: A Prospective Multicenter Italian Study. Dig Dis Sci 2024; 69:1785-1792. [PMID: 38530500 DOI: 10.1007/s10620-024-08394-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 03/16/2024] [Indexed: 03/28/2024]
Abstract
BACKGROUND Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC). AIMS Considering the number of anti-TNF non-responders, this study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52 weeks. METHODS From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events. RESULTS We included 58 patients with UC with an age of 42 ± 14.4 years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10 mg bid at W8 (p = 0.023) and W24 (p = 0.004), and with a higher partial Mayo score at W8 (p = 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation. CONCLUSIONS In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52 weeks with a good safety profile.
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Affiliation(s)
- Anna Maria Carvalhas Gabrielli
- Gastroenterology Unit, ASST Fatebenefratelli-Sacco, L. Sacco Hospital, Via Giovanni Battista Grassi, 74, 20157, Milan, MI, Italy.
| | - Francesca Ferretti
- Gastroenterology Unit, ASST Fatebenefratelli-Sacco, L. Sacco Hospital, Via Giovanni Battista Grassi, 74, 20157, Milan, MI, Italy
| | - Camilla Maria Monico
- Gastroenterology Unit, ASST Fatebenefratelli-Sacco, L. Sacco Hospital, Via Giovanni Battista Grassi, 74, 20157, Milan, MI, Italy
| | - Enrico Tombetti
- Internal Medicine and Rheumatology Unit, ASST Fatebenefratelli-Sacco, Milan, Italy
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Giovanni Maconi
- Gastroenterology Unit, ASST Fatebenefratelli-Sacco, L. Sacco Hospital, Via Giovanni Battista Grassi, 74, 20157, Milan, MI, Italy
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Samanta Romeo
- Gastroenterology and Digestive Endoscopy Dept, ASST Ospedale Maggiore Di Crema, Crema, Italy
| | - Nicole Piazza O Sed
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico Di Milano, Milan, Italy
| | - Flavio Caprioli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico Di Milano, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Anna Maria Mazzola
- Department of Clinical and Sperimental Sciences, University of Brescia, Brescia, Italy
| | - Saverio Alicante
- Gastroenterology and Digestive Endoscopy Dept, ASST Ospedale Maggiore Di Crema, Crema, Italy
| | - Roberto Bertè
- Gastroenterology and Digestive Endoscopy Dept, ASST Ospedale Maggiore Di Crema, Crema, Italy
| | - Elisabetta Lolli
- Gastroenterology Department, Policlinico Tor Vergata, Rome, Italy
| | | | - Elisabetta Buscarini
- Gastroenterology and Digestive Endoscopy Dept, ASST Ospedale Maggiore Di Crema, Crema, Italy
| | - Chiara Ricci
- Department of Clinical and Sperimental Sciences, University of Brescia, Brescia, Italy
- Gastroenterology Unit, Spedali Civili Di Brescia, Brescia, Italy
| | - Stefania Carmagnola
- Gastroenterology Unit, ASST Fatebenefratelli-Sacco, L. Sacco Hospital, Via Giovanni Battista Grassi, 74, 20157, Milan, MI, Italy
| | - Sandro Ardizzone
- Gastroenterology Unit, ASST Fatebenefratelli-Sacco, L. Sacco Hospital, Via Giovanni Battista Grassi, 74, 20157, Milan, MI, Italy
| | - Rosanna Cannatelli
- Gastroenterology Unit, ASST Fatebenefratelli-Sacco, L. Sacco Hospital, Via Giovanni Battista Grassi, 74, 20157, Milan, MI, Italy
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