The long-term effect on surgery-free survival of biological compared to conventional therapy in Crohn's disease in real world-data: a retrospective study.
Azathioprine
Biological therapy
Conventional therapy
Crohn’s disease
Mesalazine
Surgical resection
Journal
BMC gastroenterology
ISSN: 1471-230X
Titre abrégé: BMC Gastroenterol
Pays: England
ID NLM: 100968547
Informations de publication
Date de publication:
14 Dec 2023
14 Dec 2023
Historique:
received:
07
04
2023
accepted:
05
12
2023
medline:
15
12
2023
pubmed:
15
12
2023
entrez:
15
12
2023
Statut:
epublish
Résumé
The introduction of biological drugs has led to great expectations and growing optimism in the possibility that this new therapeutic strategy could favourably change the natural history of Inflammatory Bowel Disease (IBD) and, in particular, that it could lead to a significant reduction in surgery in the short and long term. This study aims to assess the impact of biological versus conventional therapy on surgery-free survival time (from the diagnosis to the first bowel resection) and on the overall risk of surgery in patients with Crohn's disease (CD) who were never with the surgical option. This is a retrospective, double-arm study including CD patients treated with either biological or conventional therapy (mesalamine, immunomodulators, antibiotics, or steroids). All CD patients admitted at the GI Unit of the S. Salvatore Hospital (L'Aquila. Italy) and treated with biological therapy since 1998 were included in the biological arm. Data concerning the CD patients receiving a conventional therapy were retrospectively collected from our database. These patients were divided into a pre-1998 and post-1998 group. Our primary outcome was the evaluation of the surgery-free survival since CD diagnosis to the first bowel resection. Surgery-free time and event incidence rates were calculated and compared among all groups, both in the original population and in the propensity-matched population. Two hundred three CD patients (49 biological, 93 conventional post-1998, 61 conventional pre-1998) were included in the study. Kaplan-Meier survivorship estimate shows that patients in the biological arm had a longer surgery-free survival compared to those in the conventional arm (p = 0.03). However, after propensity matching analysis, conducted on 143 patients, no significant difference was found in surgery-free survival (p = 0.3). A sub-group analysis showed shorter surgery-free survival in patients on conventional therapy in the pre-biologic era only (p = 0.02; Hazard Ratio 2.9; CI 1.01-8.54) while no significant difference was found between the biologic and conventional post-biologic groups (p = 0.15; Hazard Ratio 2.1; CI 0.69-6.44). This study shows that the introduction of biological therapy has only a slight impact on the eventual occurrence of surgery in CD patients over a long observation period. Nevertheless, biological therapy appears to delay the first intestinal resection.
Sections du résumé
BACKGROUND
BACKGROUND
The introduction of biological drugs has led to great expectations and growing optimism in the possibility that this new therapeutic strategy could favourably change the natural history of Inflammatory Bowel Disease (IBD) and, in particular, that it could lead to a significant reduction in surgery in the short and long term. This study aims to assess the impact of biological versus conventional therapy on surgery-free survival time (from the diagnosis to the first bowel resection) and on the overall risk of surgery in patients with Crohn's disease (CD) who were never with the surgical option.
METHODS
METHODS
This is a retrospective, double-arm study including CD patients treated with either biological or conventional therapy (mesalamine, immunomodulators, antibiotics, or steroids). All CD patients admitted at the GI Unit of the S. Salvatore Hospital (L'Aquila. Italy) and treated with biological therapy since 1998 were included in the biological arm. Data concerning the CD patients receiving a conventional therapy were retrospectively collected from our database. These patients were divided into a pre-1998 and post-1998 group. Our primary outcome was the evaluation of the surgery-free survival since CD diagnosis to the first bowel resection. Surgery-free time and event incidence rates were calculated and compared among all groups, both in the original population and in the propensity-matched population.
RESULTS
RESULTS
Two hundred three CD patients (49 biological, 93 conventional post-1998, 61 conventional pre-1998) were included in the study. Kaplan-Meier survivorship estimate shows that patients in the biological arm had a longer surgery-free survival compared to those in the conventional arm (p = 0.03). However, after propensity matching analysis, conducted on 143 patients, no significant difference was found in surgery-free survival (p = 0.3). A sub-group analysis showed shorter surgery-free survival in patients on conventional therapy in the pre-biologic era only (p = 0.02; Hazard Ratio 2.9; CI 1.01-8.54) while no significant difference was found between the biologic and conventional post-biologic groups (p = 0.15; Hazard Ratio 2.1; CI 0.69-6.44).
CONCLUSION
CONCLUSIONS
This study shows that the introduction of biological therapy has only a slight impact on the eventual occurrence of surgery in CD patients over a long observation period. Nevertheless, biological therapy appears to delay the first intestinal resection.
Identifiants
pubmed: 38097975
doi: 10.1186/s12876-023-03074-x
pii: 10.1186/s12876-023-03074-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
438Informations de copyright
© 2023. The Author(s).
Références
Maaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR guideline for diagnostic assessment in IBD part 1: initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019;13(2):144–64. https://doi.org/10.1093/ecco-jcc/jjy113 .
doi: 10.1093/ecco-jcc/jjy113
pubmed: 30137275
Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn’s disease. Lancet. 2017;389(10080):1741–55. https://doi.org/10.1016/S0140-6736(16)31711-1 .
doi: 10.1016/S0140-6736(16)31711-1
pubmed: 27914655
Turner D, Ricciuto A, Lewis A, 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(5):1570–83. https://doi.org/10.1053/j.gastro.2020.12.031 .
doi: 10.1053/j.gastro.2020.12.031
pubmed: 33359090
Valvano M, Magistroni M, Cesaro N, et al. Effectiveness of vitamin D supplementation on disease course in inflammatory bowel disease patients: systematic review with Meta-analysis. Inflamm Bowel Dis. 2022;29 https://doi.org/10.1093/ibd/izac253 .
Adamina M, Bonovas S, Raine T, et al. ECCO guidelines on therapeutics in Crohn’s disease: surgical treatment. J Crohns Colitis. 2020;14(2):155–68. https://doi.org/10.1093/ecco-jcc/jjz187 .
doi: 10.1093/ecco-jcc/jjz187
pubmed: 31742338
Bischoff SC, Barazzoni R, Busetto L, et al. European guideline on obesity care in patients with gastrointestinal and liver diseases – joint European Society for Clinical Nutrition and Metabolism / united European gastroenterology guideline. United European Gastroenterol J. 2022;10(7):663–720. https://doi.org/10.1002/ueg2.12280 .
doi: 10.1002/ueg2.12280
pubmed: 35959597
pmcid: 9486502
Vinci A, Ingravalle F, Bardhi D, et al. Cannabinoid therapeutic effects in inflammatory bowel diseases: a systematic review and Meta-analysis of randomized controlled trials. Biomedicines. 2022;10(10):2439. https://doi.org/10.3390/biomedicines10102439 .
doi: 10.3390/biomedicines10102439
pubmed: 36289701
pmcid: 9599014
Higashiyama M, Hokaria R. New and emerging treatments for inflammatory bowel disease. Digestion. 2023;104(1):74–81. https://doi.org/10.1159/000527422 .
doi: 10.1159/000527422
pubmed: 36366823
Singh S, Boland BS, Jess T, Moore AA. Management of inflammatory bowel diseases in older adults. Lancet Gastroenterol Hepatol. 2023;S2468–1253(22):00358–2. https://doi.org/10.1016/S2468-1253(22)00358-2 .
doi: 10.1016/S2468-1253(22)00358-2
Akobeng AK, Gardener E. Oral 5-aminosalicylic acid for maintenance of medically-induced remission in Crohn’s disease. In: Akobeng AK, editor. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd; 2005. https://doi.org/10.1002/14651858.CD003715.pub2 .
doi: 10.1002/14651858.CD003715.pub2
Gordon M, Naidoo K, Thomas AG, Akobeng AK. Oral 5-aminosalicylic acid for maintenance of surgically-induced remission in Crohn’s disease. Cochrane Database Syst Rev Published online January 19, 2011. doi: https://doi.org/10.1002/14651858.CD008414.pub2 .
Latella G, Caprilli R, Travis S. In favour of early surgery in Crohn’s disease: a hypothesis to be tested. J Crohns Colitis. 2011;5(1):1–4. https://doi.org/10.1016/j.crohns.2010.11.003 .
doi: 10.1016/j.crohns.2010.11.003
pubmed: 21272796
Stöss C, Berlet M, Reischl S, et al. Crohn’s disease: a population-based study of surgery in the age of biological therapy. Int J Color Dis. 2021;36(11):2419–26. https://doi.org/10.1007/s00384-021-03930-w .
doi: 10.1007/s00384-021-03930-w
Ponsioen CY, de Groof EJ, Eshuis EJ, et al. Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn’s disease: a randomised controlled, open-label, multicentre trial. Lancet Gastroenterol Hepatol. 2017;2(11):785–92. https://doi.org/10.1016/S2468-1253(17)30248-0 .
doi: 10.1016/S2468-1253(17)30248-0
pubmed: 28838644
Eberhardson M, Söderling JK, Neovius M, et al. Anti-TNF treatment in Crohn’s disease and risk of bowel resection-a population based cohort study. Aliment Pharmacol Ther. 2017;46(6):589–98. https://doi.org/10.1111/apt.14224 .
doi: 10.1111/apt.14224
pubmed: 28752637
Peyrin-Biroulet L, Loftus EV, Colombel JF, Sandborn WJ. The natural history of adult crohn’s disease in population-based cohorts. Am J Gastroenterol. 2010;105(2):289–97. https://doi.org/10.1038/ajg.2009.579 .
doi: 10.1038/ajg.2009.579
pubmed: 19861953
Murthy SK, Begum J, Benchimol EI, et al. Introduction of anti-TNF therapy has not yielded expected declines in hospitalisation and intestinal resection rates in inflammatory bowel diseases: a population-based interrupted time series study. Gut. 2020;69(2):274–82. https://doi.org/10.1136/gutjnl-2019-318440 .
doi: 10.1136/gutjnl-2019-318440
pubmed: 31196874
Jenkinson PW, Plevris N, Siakavellas S, et al. Temporal trends in surgical resection rates and biologic prescribing in Crohn’s disease: a population-based cohort study. J Crohns Colitis. 2020;14(9):1241–7. https://doi.org/10.1093/ecco-jcc/jjaa044 .
doi: 10.1093/ecco-jcc/jjaa044
pubmed: 32840295
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med. 2007;4(10):e296. https://doi.org/10.1371/journal.pmed.0040296 .
doi: 10.1371/journal.pmed.0040296
Kornbluth A. Infliximab approved for use in Crohn’s disease: a report on the fda gi advisory committee conference. Inflamm Bowel Dis. 1998;4(4):328–9. https://doi.org/10.1002/ibd.3780040415 .
doi: 10.1002/ibd.3780040415
pubmed: 9836088
D’Haens G, Van Deventer S, Van Hogezand R, et al. Endoscopic and histological healing with infliximab anti–tumor necrosis factor antibodies in Crohn’s disease: a European multicenter trial. Gastroenterology. 1999;116(5):1029–34. https://doi.org/10.1016/S0016-5085(99)70005-3 .
doi: 10.1016/S0016-5085(99)70005-3
pubmed: 10220494
Leuven E, Sianesi B. PSMATCH2: Stata module to perform full Mahalanobis and propensity score matching, common support graphing, and covariate imbalance testing. Stat Softw Compon Boston Coll Dep Econ. 2018:S432001.
Gionchetti P, Dignass A, Danese S, et al. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 2: surgical management and special situations. J Crohns Colitis. 2017;11(2):135–49. https://doi.org/10.1093/ecco-jcc/jjw169 .
doi: 10.1093/ecco-jcc/jjw169
pubmed: 27660342
Rassen JA, Shelat AA, Myers J, Glynn RJ, Rothman KJ, Schneeweiss S. One-to-many propensity score matching in cohort studies. Pharmacoepidemiol Drug Saf. 2012;21:69–80. https://doi.org/10.1002/pds.3263 .
doi: 10.1002/pds.3263
pubmed: 22552982
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53(282):457–81. https://doi.org/10.1080/01621459.1958.10501452 .
doi: 10.1080/01621459.1958.10501452
Aksan A, Farrag K, Blumenstein I, Schröder O, Dignass AU, Stein J. Chronic intestinal failure and short bowel syndrome in Crohn’s disease. World J Gastroenterol. 2021;27(24):3440–65. https://doi.org/10.3748/wjg.v27.i24.3440 .
doi: 10.3748/wjg.v27.i24.3440
pubmed: 34239262
pmcid: 8240052
Massironi S, Cavalcoli F, Rausa E, Invernizzi P, Braga M, Vecchi M. Understanding short bowel syndrome: current status and future perspectives. Dig Liver Dis. 2020;52(3):253–61. https://doi.org/10.1016/j.dld.2019.11.013 .
doi: 10.1016/j.dld.2019.11.013
pubmed: 31892505
Limketkai BN, Parian AM, Shah ND, Colombel JF. Short bowel syndrome and intestinal failure in Crohn’s disease. Inflamm Bowel Dis. 2016;22(5):1209–18. https://doi.org/10.1097/MIB.0000000000000698 .
doi: 10.1097/MIB.0000000000000698
pubmed: 26818425
Regueiro M, Schraut W, Baidoo L, et al. Infliximab prevents Crohn’s disease recurrence after Ileal resection. Gastroenterology. 2009;136(2):441–450.e1. https://doi.org/10.1053/j.gastro.2008.10.051 .
doi: 10.1053/j.gastro.2008.10.051
pubmed: 19109962
Sorrentino D, Terrosu G, Paviotti A, et al. Early diagnosis and treatment of postoperative endoscopic recurrence of Crohn’s disease: partial benefit by infiximab - a pilot study. Dig Dis Sci. 2012;57(5):1341–8. https://doi.org/10.1007/s10620-011-2025-z .
doi: 10.1007/s10620-011-2025-z
pubmed: 22252267
Savarino E, Bodini G, Dulbecco P, et al. Adalimumab is more effective than azathioprine and mesalamine at preventing postoperative recurrence of Crohn’s disease: a randomized controlled trial. Am J Gastroenterol. 2013;108(11):1731–42. https://doi.org/10.1038/ajg.2013.287 .
doi: 10.1038/ajg.2013.287
pubmed: 24019080
Sorrentino D. State-of-the-art medical prevention of postoperative recurrence of Crohn’s disease. Nat Rev Gastroenterol Hepatol. 2013;10(7):413–22. https://doi.org/10.1038/nrgastro.2013.69 .
doi: 10.1038/nrgastro.2013.69
pubmed: 23648935
Frolkis AD, Dykeman J, Negrón ME, et al. Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and Meta-analysis of population-based studies. Gastroenterology. 2013;145(5):996–1006. https://doi.org/10.1053/j.gastro.2013.07.041 .
doi: 10.1053/j.gastro.2013.07.041
pubmed: 23896172
Frolkis AD, Lipton DS, Fiest KM, et al. Cumulative incidence of second intestinal resection in Crohn’s disease: a systematic review and meta-analysis of population-based studies. Am J Gastroenterol. 2014;109(11):1739–48. https://doi.org/10.1038/ajg.2014.297 .
doi: 10.1038/ajg.2014.297
pubmed: 25331349