Difficult-to-treat inflammatory bowel disease: Effectiveness and safety of 4th and 5th lines of treatment.
Crohn's disease
inflammatory bowel disease
risankizumab
ulcerative colitis
ustekinumab
vedolizumab
Journal
United European gastroenterology journal
ISSN: 2050-6414
Titre abrégé: United European Gastroenterol J
Pays: England
ID NLM: 101606807
Informations de publication
Date de publication:
09 Apr 2024
09 Apr 2024
Historique:
received:
26
09
2023
accepted:
25
12
2023
medline:
10
4
2024
pubmed:
10
4
2024
entrez:
10
4
2024
Statut:
aheadofprint
Résumé
Many patients with inflammatory bowel disease (IBD) have signs or symptoms of active disease despite multiple treatment attempts. This emerging concept is defined as difficult-to-treat IBD. The objective of this study was to investigate for the first time the treatment persistence, efficacy and safety of biologics or small molecules used in 4th or 5th line therapy. We reviewed all consecutive patients with IBD treated at the Nancy University Hospital between July 2022 and April 2023 with the 4th or 5th line treatment for at least three months. The primary outcome was to assess the persistence rate of 4th and 5th line therapy. We enrolled 82 patients with IBD (4th line: 44; 5th line: 38). On Kaplan-Meier analysis, the duration of risankizumab, ustekinumab or vedolizumab therapy did not differ significantly (p > 0.05) as 4th and 5th line treatment. The restricted mean survival time analysis showed that the persistence rate of risankizumab was the highest as 4th line therapy (risankizumab vs. vedolizumab: 36.0 and 29.4 weeks, respectively, p = 0.008; risankizumab vs. ustekinumab: 36.0 and 32.8 weeks, respectively, p = 0.035). In multivariate regression, Crohn's disease diagnosis (Odd ratio 4.6; 95% confidence interval 1.7-12.4) was significantly associated with treatment persistence. In this first real-world setting, risankizumab could have a longer persistence rate as 4th line treatment for IBD than other agents. Persistence of biological agents was greater in Crohn's disease than in ulcerative colitis. More studies are needed to compare treatment efficacy in patients with difficult-to-treat IBD.
Sections du résumé
BACKGROUND
BACKGROUND
Many patients with inflammatory bowel disease (IBD) have signs or symptoms of active disease despite multiple treatment attempts. This emerging concept is defined as difficult-to-treat IBD.
AIM
OBJECTIVE
The objective of this study was to investigate for the first time the treatment persistence, efficacy and safety of biologics or small molecules used in 4th or 5th line therapy.
METHODS
METHODS
We reviewed all consecutive patients with IBD treated at the Nancy University Hospital between July 2022 and April 2023 with the 4th or 5th line treatment for at least three months. The primary outcome was to assess the persistence rate of 4th and 5th line therapy.
RESULTS
RESULTS
We enrolled 82 patients with IBD (4th line: 44; 5th line: 38). On Kaplan-Meier analysis, the duration of risankizumab, ustekinumab or vedolizumab therapy did not differ significantly (p > 0.05) as 4th and 5th line treatment. The restricted mean survival time analysis showed that the persistence rate of risankizumab was the highest as 4th line therapy (risankizumab vs. vedolizumab: 36.0 and 29.4 weeks, respectively, p = 0.008; risankizumab vs. ustekinumab: 36.0 and 32.8 weeks, respectively, p = 0.035). In multivariate regression, Crohn's disease diagnosis (Odd ratio 4.6; 95% confidence interval 1.7-12.4) was significantly associated with treatment persistence.
CONCLUSION
CONCLUSIONS
In this first real-world setting, risankizumab could have a longer persistence rate as 4th line treatment for IBD than other agents. Persistence of biological agents was greater in Crohn's disease than in ulcerative colitis. More studies are needed to compare treatment efficacy in patients with difficult-to-treat IBD.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.
Références
Roda G, Chien Ng S, Kotze PG, Argollo M, Panaccione R, Spinelli A, et al. Crohn’s disease. Nat Rev Dis Primers. 2020;6(1):22. https://doi.org/10.1038/s41572‐020‐0156‐2
Le Berre C, Honap S, Peyrin‐Biroulet L. Ulcerative colitis. Lancet. 2023;402(10401):571–584. https://doi.org/10.1016/S0140‐6736(23)00966‐2
Singh S, George J, Boland BS, Vande Casteele N, Sandborn WJ. Primary non‐response to tumor necrosis factor antagonists is associated with inferior response to second‐line biologics in patients with inflammatory bowel diseases: a systematic review and meta‐analysis. J Crohns Colitis. 2018;12(6):635–643. https://doi.org/10.1093/ecco‐jcc/jjy004
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(12):1002–1014. https://doi.org/10.1016/S2468‐1253(21)00312‐5
Danese S, Parigi TL, Peyrin‐Biroulet L, Ghosh S. Defining difficult‐to‐treat inflammatory bowel disease: why and how. Lancet Gastroenterol Hepatol. 2021;6(7):520–522. https://doi.org/10.1016/S2468‐1253(21)00141‐2
Parigi TL, D’Amico F, Abreu MT, Rubin DT, Dignass A, Dotan I, et al. Difficult‐to‐treat inflammatory bowel disease: results from a global IOIBD survey. Lancet Gastroenterol Hepatol. 2022;7(5):390–391. https://doi.org/10.1016/S2468‐1253(22)00085‐1
Allez M, Vermeire S, Mozziconacci N, Michetti P, Laharie D, Louis E, et al. The efficacy and safety of a third anti‐TNF monoclonal antibody in Crohn’s disease after failure of two other anti‐TNF antibodies. Aliment Pharmacol Therapeut. 2010;31(1):92–101. https://doi.org/10.1111/j.1365‐2036.2009.04130.x
Parrot L, Dong C, Carbonnel F, Meyer A. Systematic review with meta‐analysis: the effectiveness of either ustekinumab or vedolizumab in patients with Crohn’s disease refractory to anti‐tumour necrosis factor. Aliment Pharmacol Ther. 2022;55(4):380–388. https://doi.org/10.1111/apt.16714
Amiot A, Serrero M, Peyrin‐Biroulet L, Filippi J, Pariente B, Roblin X, et al. One‐year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicentre cohort study. Aliment Pharmacol Therapeut. 2017;46(3):310–321. https://doi.org/10.1111/apt.14167
Wils P, Bouhnik Y, Michetti P, Flourie B, Brixi H, Bourrier A, et al. Long‐term efficacy and safety of ustekinumab in 122 refractory Crohn’s disease patients: a multicentre experience. Aliment Pharmacol Ther. 2018;47(5):588–595. https://doi.org/10.1111/apt.14487
Macaluso FS, Grova M, Saladino M, Cappello M, Demarzo MG, Privitera AC, et al. The effectiveness of ustekinumab and vedolizumab as third‐line biologic therapy in patients with Crohn’s disease. Dig Liver Dis. 2023;55(4):471–477. https://doi.org/10.1016/j.dld.2022.08.028
Gisbert JP, Marín AC, McNicholl AG, Chaparro M. Systematic review with meta‐analysis: the efficacy of a second anti‐TNF in patients with inflammatory bowel disease whose previous anti‐TNF treatment has failed. Aliment Pharmacol Ther. 2015;41(7):613–623. https://doi.org/10.1111/apt.13083
Gregson J, Sharples L, Stone GW, Burman CF, Öhrn F, Pocock S. Nonproportional hazards for time‐to‐event outcomes in clinical trials: JACC review topic of the week. J Am Coll Cardiol. 2019;74(16):2102–2112. https://doi.org/10.1016/j.jacc.2019.08.1034
Nagy G, Roodenrijs NM, Welsing PM, Kedves M, Hamar A, van der Goes MC, et al. EULAR definition of difficult‐to‐treat rheumatoid arthritis. Ann Rheum Dis. 2021;80(1):31–35. https://doi.org/10.1136/annrheumdis‐2020‐217344
Takanashi S, Kaneko Y, Takeuchi T. Characteristics of patients with difficult‐to‐treat rheumatoid arthritis in clinical practice. Rheumatol. 2021;60(11):5247–5256. https://doi.org/10.1093/rheumatology/keab209
Ferges W, Rampertab SD, Shafqet M, Salimi Q, You G, Yousefzadeh E, et al. Experience with anti‐TNF‐α biologic agents in succession in patients with Crohn’s disease: a retrospective analysis of a single center. J Clin Gastroenterol. 2016;50(4):326–330. https://doi.org/10.1097/MCG.0000000000000338
Albshesh A, Taylor J, Savarino EV, Truyens M, Armuzzi A, Ribaldone DG, et al. Effectiveness of third‐class biologic treatment in Crohn’s disease: a multi‐center retrospective cohort study. J Clin Med. 2021;10(13):2914. https://doi.org/10.3390/jcm10132914
Kassouri L, Amiot A, Kirchgesner J, Tréton X, Allez M, Bouhnik Y, et al. The outcome of Crohn’s disease patients refractory to anti‐TNF and either vedolizumab or ustekinumab. Dig Liver Dis. 2020;52(10):1148–1155. https://doi.org/10.1016/j.dld.2020.07.031
Raine T, Verstockt B, Kopylov U, Karmiris K, Goldberg R, Atreya R, et al. ECCO topical review: refractory inflammatory bowel disease. J Crohns Colitis. 2021;15(10):1605–1620. https://doi.org/10.1093/ecco‐jcc/jjab112
Parigi TL, D’Amico F, Abreu MT, Dignass A, Dotan I, Magro F, et al. Difficult‐to‐treat inflammatory bowel disease: results from an international consensus meeting. Lancet Gastroenterol Hepatol. 2023;8(9):853–859. Epub 2023 Jul 6. PMID: 37423233. https://doi.org/10.1016/S2468‐1253(23)00154‐1