Editorial: Individualising JAK Inhibitor Selection for Patients With Ulcerative Colitis

Alimentary Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Tofacitinib, upadacitinib, and filgotinib are the Janus kinase (JAK) inhibitors currently approved for ulcerative colitis (UC). All have distinct JAK selectivity show robust efficacy [1-3]. However, they associated with adverse events including increased risk of cancer, Herpes zoster infection, major cardiovascular [1-4]. Moreover, similar to anti-TNF therapy, increase vaccine-preventable diseases by impairing immune responses elicited immunisation [5, 6]. Given these concerns, FDA recommends restricting patients who had previously been non-responsive at least one other advanced therapy. Akiyama et al. evaluated safety tofacitinib, filgotinib, upadacitinib in a multi-centre cohort Japanese UC identify predictors drug discontinuation improve guidance on positioning [7]. Using logistic regression analyses propensity score-matched cohorts, showed that was more effective than tofacitinib filgotinib. Additionally, identified an inverse association between number previous therapies but not upadacitinib. The comparable among groups, acne. high may suggest its suitability as first-line inhibitor. since filgotinib—but upadacitinib—is reduced prior therapies, their chances success be higher if used before rather after Therefore, using inhibitor suitable option therapy-experienced whom lower while, little therapy experience, might second- or third-line case non-responsiveness Additional research is required define further effectiveness those exposed tofacitinib. Considering differences genetic architecture IBD Asian European ancestry, which includes genes affected (e.g., JAK2, TYK2, STAT3), genetics also affect [8]. Although many treatment studies were carried out populations, authors provided valuable insights into population. results aligned two meta-analyses demonstrating moderate-to-severe consistent our personal experience [9, 10]. Filgotinib platelet count—possibly indicative milder disease activity—which important finding light personalised Improving understanding cellular molecular factors contributing failure help disentangle underlying mechanisms aid individualised selection inhibitors. In summary, advice how sequence paved way inhibition IBD. Simon Woelfel: writing – original draft, review editing, conceptualization, investigation, formal analysis. Stephan Brand: supervision, Brand received speaker's honoraria from Abbvie, Falk Foundation, Ferring, Janssen, Lilly, MSD, Takeda, UCB, Vifor participated advisory boards BMS, Celgene, Pfizer, Pierre Fabre, Roche, UCB. SB has educational grant Takeda. funders no role design study; collection, interpretation data; manuscript decision publish results. This article linked al papers. To view articles, visit https://doi.org/10.1111/apt.18406 https://doi.org/10.1111/apt.18489. Data sharing applicable this new data created analyzed study.

Language: Английский

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Letter: Toward Intra‐Class Switching With JAK Inhibitors?

Alimentary Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Language: Английский

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Editorial: Individualising JAK Inhibitor Selection for Patients With Ulcerative Colitis—Authors' Reply

Alimentary Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

We thank Woelfel et al [1] for their interest and comments on our research article [2]. demonstrated superior efficacy of upadacitinib over two other Janus kinase (JAK) inhibitors in ulcerative colitis (UC). As stated [1], results suggest that may be suitable patients with UC who have failed multiple biologics JAK inhibitors. However, the risk acne was highest among three drugs While we showed Herpes zoster (HZ) infection comparable drugs, a network meta-analysis risks HZ tofacitinib were higher than filgotinib [3]. Considering such upadacitinib, it is better to use or are naïve advanced therapy those had one biologics. found lower number previous therapies was, tofacitinib. In study, there no data clinical remission rate 50% at most recent follow-up (52 weeks) after inhibitor use, only 21 included analysis. Therefore, agree more needed understand previously exposed different platelet counts less [2, 4]. The median count 30 x 10 [4]/μl achieved 33 did not. possible underlying mechanism selection based (Figure 1). JAK2-mediated signalling important production reflect active inflammatory [5]. Since has JAK1 selectivity [5], inhibitory activity against 1A), resulting counts. Our result suggests if > [4]/μl, prefer choose instead filgotinib, as these 1B). finding an step understanding individualised UC. pointed out by because genetic architectures, including genes affected (e.g., JAK2), between Asian European ancestries [6], further investigation warranted generalise findings. (A) Relationship cytokine receptors kinases (JAKs). inhibitors, this drug compared upadacitinib. (B) Selection If laboratory show [4]/μl), signalling. EPO, erythropoietin; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin; JAK, kinase; TYK2, tyrosine 2. authors' declarations personal financial interests unchanged from original S.A. drafted article. T.F. critically revised manuscript. authors nothing report. None. This linked Akiyama papers. To view articles, visit https://doi.org/10.1111/apt.18406 https://doi.org/10.1111/apt.18476. Data sharing not applicable new created analyzed study.

Language: Английский

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Letter: Toward Intra‐Class Switching With JAK Inhibitors? Authors' Reply

Alimentary Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

We thank Dr. Uzzan et al. [1] for their comments on our publication [2]. have clarified the data availability regarding intra-class switching with Janus kinase (JAK) inhibitors in study (Figure 1). demonstrated efficacy of upadacitinib ulcerative colitis (UC) after use tofacitinib and filgotinib As a result, upadacitinib-treated patients showed clinical remission rate 71.9% (64/89) at most recent follow-up (median 53 weeks). This suggests that can be considered or filgotinib. Given highest among three JAK UC [2], opposite approaches may not reasonable. also assessed other inhibitors, predominantly [2, 3]; filgotinib-treated 50% (10/20) 52 weeks) Our results indicate could offer chance to achieve previously exposed tofacitinib. pointed out, we did evaluate who had been treated as primarily collected from started within first 18 months following approval each drug Japan. Tofacitinib was approved 2018 inhibitor UC; therefore, there were no its filgotinib, which 2022. To best knowledge, real-world specifically addressing this issue, number comparative studies between is limited. analysis using propensity score matching some outcomes (e.g., response 10 26 weeks, well endoscopic improvement) appeared better than although differences statistically significant. In addition, Yagi [4] more effective 8 weeks respond therapy 4 weeks. These findings suggest an option agree are needed understand cycling strategy UC, look forward seeing European Crohn's Colitis Organisation [1]. The authors' declarations personal financial interests unchanged those original article Shintaro Akiyama: writing – draft, review editing. Toshimitsu Fujii: authors nothing report. linked Akiyama al papers. view these articles, visit https://doi.org/10.1111/apt.18406 https://doi.org/10.1111/apt.18518. Data sharing applicable datasets generated analysed during current study.

Language: Английский

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Effectiveness and Safety of a Second JAK Inhibitor in Ulcerative Colitis: The J2J Multicentre Study

Alimentary Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: May 22, 2025

While three Janus kinase inhibitors (JAKi) have demonstrated efficacy in ulcerative colitis (UC), scarce data exist regarding JAKi intraclass switching. To evaluate the effectiveness and safety of a second JAK inhibitor UC. This was multicentre, retrospective, observational cohort including patients with moderate to severe UC who received second-line after failure or intolerance first. The primary outcome steroid-free clinical remission (SFCR) at Weeks 8-14, defined as partial Mayo score 2 less no individual sub-score above 1. Among 169 from 28 participating centres, 105 upadacitinib, 54 filgotinib 10 tofacitinib JAKi. Overall, 81/169 achieved SFCR 8-14: 58/105 18/54 5/10 (p = 0.03). In multivariate analysis, upadacitinib independently associated higher odds than (OR 3.15, 95% CI [1.52-6.79]). With median follow-up duration 96 days, drug persistence 6 months 72.8% 57.2% 66.7% 0.099). 24.3% (41/169) experienced least one adverse event leading treatment withdrawal 9 (5%). No cases death, cancer, major acute cardiovascular events were reported. A provided about half induction, well tolerated.

Language: Английский

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First Documented Case of Successful Dual Therapy With Upadacitinib and Mirikizumab for Multi-Refractory Ulcerative Proctitis

Inflammatory Bowel Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: May 24, 2025

This article reports the first documented case of successful dual therapy with upadacitinib (JAK inhibitor) and mirikizumab (anti-IL-23) for multi-refractory ulcerative proctitis, demonstrating clinical remission, biomarker normalization, endoscopic improvement after failure conventional therapies.

Language: Английский

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