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. 2024 Jun;12(5):605-613.
doi: 10.1002/ueg2.12547. Epub 2024 Apr 9.

Difficult-to-treat inflammatory bowel disease: Effectiveness and safety of 4th and 5th lines of treatment

Bénédicte Caron  1   2   3   4 , Alexandre Habert  1 , Olivier Bonsack  1 , Houda Camara  5 , Elodie Jeanbert  5 , Tommaso Lorenzo Parigi  6   7 , Patrick Netter  8 , Silvio Danese  6   7 , Laurent Peyrin-Biroulet  1   2   3   4   9
Affiliations

Difficult-to-treat inflammatory bowel disease: Effectiveness and safety of 4th and 5th lines of treatment

Bénédicte Caron et al. United European Gastroenterol J. 2024 Jun.

Abstract

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: 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: 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: 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: 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.

Keywords: Crohn's disease; inflammatory bowel disease; risankizumab; ulcerative colitis; ustekinumab; vedolizumab.

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Conflict of interest statement

Bénédicte Caron has received lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Ferring, Galapagos, Janssen, Lilly, and Takeda. Alexandre Habert declares no conflict of interest. Olivier Bonsack declares no conflict of interest. Houda Camara declares no conflict of interest and Elodie Jeanbert declares no conflict of interest. Tommaso Lorenzo Parigi declares no conflict of interest. Patrick Netter declares no conflict of interest. Silvio Danese has served as a speaker, consultant, and advisory board member for Schering‐Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor. Laurent Peyrin‐Biroulet declares consulting: from AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC‐Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax; grants from Takeda, Fresenius Kabi, Celltrion; lecture from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, Medac; support travel from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Gossamer Bio, Sandoz, MSD, Amgen, Lilly, Gilead, Thermo Fisher, Medac, CONNECT Biopharm; and stock options from CTMA.

Figures

FIGURE 1
FIGURE 1
Kaplan–Meier survival estimates for discontinuation in patients receiving 4th and 5th line treatment.
See this image and copyright information in PMC

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