Short term effectiveness of ustekinumab versus vedolizumab in Crohn's disease after failure of anti-TNF agents: An observational comparative study design with a Bayesian analysis.
Journal
Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association
ISSN: 1998-4049
Titre abrégé: Saudi J Gastroenterol
Pays: India
ID NLM: 9516979
Informations de publication
Date de publication:
19 Aug 2024
19 Aug 2024
Historique:
received:
17
03
2024
accepted:
22
07
2024
medline:
19
8
2024
pubmed:
19
8
2024
entrez:
19
8
2024
Statut:
aheadofprint
Résumé
Crohn's disease (CD) is a debilitating gastrointestinal disease with complex etiology. Although effective, recipients of anti-tumor necrosis factor (TNF) agents may experience primary or secondary nonresponse, necessitating alternative treatments. This study is intended to compare the short-term effectiveness of ustekinumab and vedolizumab in treating CD after failure of multiple lines of anti-TNF therapy using real-world data. A retrospective study was conducted at a tertiary hospital in Dammam, Saudi Arabia, including adults (≥18 years old) with CD who did not respond to anti-TNF therapy. Primary endpoints were clinical improvement per the Harvey-Bradshaw Index (HBI) scores and remission at 12 weeks on an ordinal outcome scale. Secondary endpoints included clinical, biochemical, and endoscopic remission; clinical response; corticosteroid-free days; and cumulative steroid dose. Proportional odds and logistic regression Bayesian models were used to analyze outcomes, and the probability of treatment effectiveness was calculated from the posterior distribution. The study included 101 patients (ustekinumab, n = 71 and vedolizumab, n = 30) with a median age of 32 years (IQR: 26.0-38.0); 54.4% were male. At 12 weeks, the HBI endpoint showed an adjusted odds ratio (aOR) = 0.60 (95% confidence interval [CI]: 0.25-1.31), favoring ustekinumab, with a 75% probability of treatment effectiveness over vedolizumab. The clinical ordinal scale had an aOR = 0.61 (95% CI: 0.26-1.35) with a 73% probability of effectiveness for ustekinumab. Ustekinumab was also associated with favorable outcomes in secondary endpoints, reaching up to a 90% probability of effectiveness. In CD patients with anti-TNF failure, ustekinumab was more effective than vedolizumab in the short term. These real-world insights contribute to understanding CD management but require validation in larger prospective studies and randomized controlled trials.
Sections du résumé
BACKGROUND
BACKGROUND
Crohn's disease (CD) is a debilitating gastrointestinal disease with complex etiology. Although effective, recipients of anti-tumor necrosis factor (TNF) agents may experience primary or secondary nonresponse, necessitating alternative treatments. This study is intended to compare the short-term effectiveness of ustekinumab and vedolizumab in treating CD after failure of multiple lines of anti-TNF therapy using real-world data.
METHODS
METHODS
A retrospective study was conducted at a tertiary hospital in Dammam, Saudi Arabia, including adults (≥18 years old) with CD who did not respond to anti-TNF therapy. Primary endpoints were clinical improvement per the Harvey-Bradshaw Index (HBI) scores and remission at 12 weeks on an ordinal outcome scale. Secondary endpoints included clinical, biochemical, and endoscopic remission; clinical response; corticosteroid-free days; and cumulative steroid dose. Proportional odds and logistic regression Bayesian models were used to analyze outcomes, and the probability of treatment effectiveness was calculated from the posterior distribution.
RESULTS
RESULTS
The study included 101 patients (ustekinumab, n = 71 and vedolizumab, n = 30) with a median age of 32 years (IQR: 26.0-38.0); 54.4% were male. At 12 weeks, the HBI endpoint showed an adjusted odds ratio (aOR) = 0.60 (95% confidence interval [CI]: 0.25-1.31), favoring ustekinumab, with a 75% probability of treatment effectiveness over vedolizumab. The clinical ordinal scale had an aOR = 0.61 (95% CI: 0.26-1.35) with a 73% probability of effectiveness for ustekinumab. Ustekinumab was also associated with favorable outcomes in secondary endpoints, reaching up to a 90% probability of effectiveness.
CONCLUSION
CONCLUSIONS
In CD patients with anti-TNF failure, ustekinumab was more effective than vedolizumab in the short term. These real-world insights contribute to understanding CD management but require validation in larger prospective studies and randomized controlled trials.
Identifiants
pubmed: 39157885
doi: 10.4103/sjg.sjg_101_24
pii: 00936815-990000000-00097
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Copyright: © 2024 Saudi Journal of Gastroenterology.
Références
Pariente B, Mary J-Y, Danese S, Chowers Y, De Cruz P, D'Haens G, et al. Development of the Lémann index to assess digestive tract damage in patients with crohn's disease. Gastroenterology 2015; 148:52–63 e3.
Peyrin-Biroulet L, Cieza A, Sandborn WJ, Coenen M, Chowers Y, Hibi T, et al. Development of the first disability index for inflammatory bowel disease based on the international classification of functioning, disability and health. Gut 2012; 61:241–7.
Dolinger M, Torres J, Vermeire S. Crohn's disease. Lancet 2024; 403:1177–91.
Kaplan GG, Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2021; 18:56–66. doi:10.1038/s41575-020-00360-x.
doi: 10.1038/s41575-020-00360-x
Le Berre C, Honap S, Peyrin-Biroulet L. Ulcerative colitis. Lancet 2023; 402:571–84.
Chang JT. Pathophysiology of inflammatory bowel diseases. N Engl J Med 2020; 383:2652–64.
D'Haens GR, van Deventer S. 25 years of anti-TNF treatment for inflammatory bowel disease:Lessons from the past and a look to the future. Gut 2021; 70:1396–405.
Mosli MH, Almudaiheem HY, AlAmeel T, Bakkari SA, Alharbi OR, Alenzi KA, et al. Saudi Arabia consensus guidance for the diagnosis and management of adults with inflammatory bowel disease. Saudi J Gastroenterol 2022; 29 (Suppl 1): S1–35.
AbbVie News Center SKYRIZI®(risankizumab-rzaa) receives FDA approval as the first and only specific interleukin-23 (IL-23) to treat moderately to severely active crohn's disease in adults. Available from:https://news.abbvie.com/2022-06-17-SKYRIZI-R-risankizumab-rzaa-Receives-FDA-Approval-as-the-First-and-Only-Specific-Interleukin-23-IL-23-to-Treat-Moderately-to-Severely-Active-Crohns-Disease-in-Adults.. [Last acessed on 2024 Jun 12].
FDA approves first oral treatment for moderately to severely active Crohn's disease. U. S. Food and Drug Administration. FDA 2023. Available from:https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-oral-treatment-moderately-severely-active-crohns-disease. [Last acessed on 2024 Jun 12].
Gordon H, Minozzi S, Kopylov U, Verstockt B, Chaparro M, Buskens C, et al. ECCO Guidelines on Therapeutics in Crohn's Disease:Medical Treatment. J Crohns Colitis 2024 jjae091.
Feuerstein JD, Ho EY, Shmidt E, Singh H, Falck-Ytter Y, Sultan S, et al. AGA clinical practice guidelines on the medical management of moderate to severe luminal and perianal fistulizing Crohn's disease. Gastroenterology 2021; 160:2496–508.
Ben-Horin S, Kopylov U, Chowers Y. Optimizing anti-TNF treatments in inflammatory bowel disease. Autoimmun Rev 2014; 13:24–30.
Hyun HK, Zhang H-S, Yu J, Kang EA, Park J, Park SJ, et al. Comparative effectiveness of second-line biological therapies for ulcerative colitis and Crohn's disease in patients with prior failure of anti-tumour necrosis factor treatment. BMC Gastroenterol 2022; 22:143.
Dulai PS, Mosli M, Khanna R, Levesque BG, Sandborn WJ, Feagan BG. Vedolizumab for the treatment of moderately to severely active ulcerative colitis. Pharmacotherapy 2015; 35:412–23.
Teng MWL, Bowman EP, McElwee JJ, Smyth MJ, Casanova J-L, Cooper AM, et al. IL-12 and IL-23 cytokines:From discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med 2015; 21:719–29.
Pagnini C, Siakavellas SI, Bamias G. Systematic review with network meta-analysis:Efficacy of induction therapy with a second biological agent in anti-TNF-experienced Crohn's disease patients. Gastroenterol Res Pract 2018; 2018:1–9.
Pacou M, Mesana L, Gauthier A, Naessens D, Sloan S, Danese S, et al. Indirect treatment comparison of ustekinumab versus other biologics in moderate to severe Crohn's disease:A 1-year treatment sequence analysis. Value Health 2016; 19:A576.
García MJ, Rivero M, Fernández-Clotet A, de Francisco R, Sicilia B, Mesonero F, et al. Comparative study of the effectiveness of vedolizumab versus ustekinumab after anti-TNF failure in Crohn's disease (versus-CD):Data from the ENEIDA registry. J Crohns Colitis 2024; 18:65–74.
Biemans VBC, van der Woude CJ, Dijkstra G, van der Meulen-de Jong AE, Löwenberg M, de Boer NK, et al. Ustekinumab is associated with superior effectiveness outcomes compared to vedolizumab in Crohn's disease patients with prior failure to anti-TNF treatment. Aliment Pharmacol Ther 2020; 52:123–34.
Baumgart DC, Bokemeyer B, Drabik A, Stallmach A, Schreiber S. Vedolizumab Germany Consortium. Vedolizumab induction therapy for inflammatory bowel disease in clinical practice--A nationwide consecutive German cohort study. Aliment Pharmacol Ther 2016; 43:1090–102.
Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal classification of inflammatory bowel disease:Controversies, consensus, and implications. Gut 2006; 55:749–53.
Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019; 68 (Suppl 3): s1 106.
Peyrin-Biroulet L, Panés J, Sandborn WJ, Vermeire S, Danese S, Feagan BG, et al. Defining disease severity in inflammatory bowel diseases:Current and future directions. Clin Gastroenterol Hepatol 2016; 14:348–54 e17.
Allegretti JR, Barnes EL, Stevens B, Storm M, Ananthakrishnan A, Yajnik V, et al. Predictors of clinical response and remission at 1 year among a multicenter cohort of patients with inflammatory bowel disease treated with vedolizumab. Dig Dis Sci 2017; 62:1590–6.
Teresa VD, Rául OM, Marisa I, Claudia HG, Esteban FV, Luigi M, et al. Effectiveness and safety of ustekinumab in bio-naïve Crohn's disease patients:A multicentre observational retrospective study. Therap Adv Gastroenterol 2023; 16:17562848231153560.
Turner D, Ricciuto A, Lewis A, D'Amico F, Dhaliwal J, Griffiths AM, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of IBD (IOIBD):Determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology 2021; 160:1570–83.
Colombel J-F, Panaccione R, Bossuyt P, Lukas M, Baert F, Vaňásek T, et al. Effect of tight control management on Crohn's disease (CALM):A multicentre, randomised, controlled phase 3 trial. Lancet 2017; 390:2779–89.
Sands BE, Irving PM, Hoops T, Izanec JL, Gao L-L, Gasink C, et al. Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease:A multicentre, randomised, double-blind, parallel-group, phase 3b trial. Lancet 2022; 399:2200–11.
Abreu MT, Sandborn WJ;IOIBD Defining Endpoints and Biomarkers in Inflammatory Bowel Disease Writing Group. Defining endpoints and biomarkers in inflammatory bowel disease:Moving the needle through clinical trial design. Gastroenterology 2020; 159:2013–8.e7.
Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, et al. Ustekinumab as induction and maintenance therapy for Crohn's disease. N Engl J Med 2016; 375:1946–60.
Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, et al. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med 2013; 369:711–21.
Hmisc: Harrel Miscellaneous. Available from:https://cran.r-project.org/web/packages/Hmisc/index.html. [Last accessed on 2024 Jun 21].
Tennant PWG, Murray EJ, Arnold KF, Berrie L, Fox MP, Gadd SC, et al. Use of directed acyclic graphs (DAGs) to identify confounders in applied health research:review and recommendations. Int J Epidemiol 2021; 50:620–32.
Textor J. Drawing and analyzing causal DAGs with DAGitty arXiv [cs. AI] 2015. Available from:http://arxiv.org/abs/1508.04633. [Last accessed on 2024 Jun 21].
Kawalec P, Moćko P. An indirect comparison of ustekinumab and vedolizumab in the therapy of TNF-failure Crohn's disease patients. J Comp Eff Res 2018; 7:101–11.
Singh S, Fumery M, Sandborn WJ, Murad MH. Systematic review and network meta-analysis:first- and second-line biologic therapies for moderate-severe Crohn's disease. Aliment Pharmacol Ther 2018; 48:394–409.
Singh S, Murad MH, Fumery M, Sedano R, Jairath V, Panaccione R, et al. Comparative efficacy and safety of biologic therapies for moderate-to-severe Crohn's disease: A systematic review and network meta-analysis. Lancet Gastroenterol Hepatol 2021; 6:1002–14.
Yang H, Huang Z, Li M, Zhang H, Fu L, Wang X, et al. Comparative effectiveness of ustekinumab vs. vedolizumab for anti-TNF-naïve or anti-TNF-exposed Crohn's disease:a multicenter cohort study. EclinicalMedicine 2023; 66:102337.
Alric H, Amiot A, Kirchgesner J, Tréton X, Allez M, Bouhnik Y, et al. The effectiveness of either ustekinumab or vedolizumab in 239 patients with Crohn's disease refractory to anti-tumour necrosis factor. Aliment Pharmacol Ther 2020; 51:948–57.
Sandborn WJ, Gasink C, Gao L-L, Blank MA, Johanns J, Guzzo C, et al. Ustekinumab induction and maintenance therapy in refractory Crohn's disease. N Engl J Med 2012; 367:1519–28.
Balzola F, Cullen G, Ho GT, Russell R. Vedolizumab as induction and maintenance therapy for Crohn's disease: Commentary. Commentary Inflamm Bowel 2014; 14:55–6.
Wasserstein R, Statistician N. The ASA statement on P values:Context, process, and purpose. Am Stat 2016; 70:129–33.
Sharip MT, Nishad N, Pillay L, Goordoyel N, Goerge S, Subramanian S. Ustekinumab or vedolizumab after failure of anti-TNF agents in Crohn's disease:A review of comparative effectiveness studies. J Clin Med 2024; 13:2187.