Intest Res.  2018 Jan;16(1):62-68. 10.5217/ir.2018.16.1.62.

Comparison of time until elective intestinal resection regarding previous anti-tumor necrosis factor exposure: a Brazilian study on patients with Crohn's disease

• Kotze PG
• Magro DO
• Saab B
• Saab MP
• Pinheiro L
• Olandoski
• Ayrizono M
• Martinez C
• Coy CS

• KMID: 2402648
• DOI: http://doi.org/10.5217/ir.2018.16.1.62

Abstract

BACKGROUND/AIMS
The use of anti-tumor necrosis factor (anti-TNF) agents seems to reduce surgical rates and delay surgical procedures in prospective trials and population-based studies in the management of Crohn's disease (CD). This study aimed to identify whether preoperative anti-TNF agents influence the time from diagnosis to surgery.
METHODS
An observational retrospective cohort study was conducted on patients with CD submitted to intestinal resections due to complications or medical therapy failure in a period of 7 years. The patients were allocated into 2 groups according to their previous exposure to anti-TNF agents in the preoperative period. Epidemiological aspects regarding age at diagnosis, smoking, perianal disease, and preoperative conventional therapy were considered. A Kaplan-Meier survival analysis was used to outline possible differences between the groups regarding the time to surgery.
RESULTS
A total of 123 patients were included (71 and 52 with and without previous exposure to biologics, respectively). The overall time to surgery was 108±6.9 months (maximum, 276 months). The survival estimation revealed no difference in the mean time to intestinal resection between the groups (99.78±10.62 months in the patients without and 114.01±9.07 months in those with previous anti-TNF use) (log-rank P=0.35). There was no significant difference in the time to surgery regarding perianal CD (P=0.49), smoking (P=0.63), preoperative azathioprine (P=0.073) and steroid use (P=0.58).
CONCLUSIONS
The time from diagnosis to surgery was not influenced by the preoperative use of anti-TNF therapy in this cohort of patients.

Keyword

Crohn disease; Tumor necrosis factor-alpha; Surgical procedures, operative; Survival analysis

MeSH Terms

Azathioprine
Biological Products
Cohort Studies
Crohn Disease*
Diagnosis
Humans
Necrosis*
Preoperative Period
Prospective Studies
Retrospective Studies
Smoke
Smoking
Surgical Procedures, Operative
Survival Analysis
Tumor Necrosis Factor-alpha
Azathioprine
Biological Products
Smoke
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 Study flowchart and group definition. TNF, tumor necrosis factor.

• 

  Fig. 2 Kaplan-Meier curves demonstrating different analyses. (A) Time between diagnosis and surgery according to the use of anti-tumor necrosis factor (anti-TNF) agents ([−], without; [+], with) (log-rank P=0.35). (B) Time from diagnosis to surgery between the 2 different anti-TNF agents (infliximab [IFX] and adalimumab [ADA]). The patients under ADA therapy have longer disease durations until surgery (log-rank P=0.034). (C) Time interval until surgery between the patients under ADA and conventional therapy (log-rank P=0.69). (D) Time from diagnosis to surgery between the patients with and without previous exposure to azathioprine (AZA) ([−], without; [+], with) (log-rank P=0.073). (E) Time interval until surgery between the patients with and without preoperative exposure to steroids ([−], without; [+], with) (log-rank P=0.58). (F) Time from diagnosis to surgery between the patients under preoperative monotherapy and combotherapy (log-rank P=0.35).

Reference

1. Khanna R, Bressler B, Levesque BG, et al. Early combined immunosuppression for the management of Crohn's disease (REACT): a cluster randomised controlled trial. Lancet. 2015; 386:1825–1834. PMID: 26342731.

2. Pariente B, Cosnes J, Danese S, et al. Development of the Crohn's disease digestive damage score, the Lemann score. Inflamm Bowel Dis. 2011; 17:1415–1422. PMID: 21560202.

3. Kotze PG, Saab MP, Saab B, et al. Tumor necrosis factor alpha inhibitors did not influence postoperative morbidity after elective surgical resections in Crohn's disease. Dig Dis Sci. 2017; 62:456–464. PMID: 27933472.

4. Ramadas AV, Gunesh S, Thomas GA, Williams GT, Hawthorne AB. Natural history of Crohn's disease in a population-based cohort from Cardiff (1986-2003): a study of changes in medical treatment and surgical resection rates. Gut. 2010; 59:1200–1206. PMID: 20650924.

5. Rungoe C, Langholz E, Andersson M, et al. Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979-2011. Gut. 2014; 63:1607–1616. PMID: 24056767.

6. Olivera P, Spinelli A, Gower-Rousseau C, Danese S, Peyrin-Biroulet L. Surgical rates in the era of biological therapy: up, down or unchanged? Curr Opin Gastroenterol. 2017; 33:246–253. PMID: 28463854.

7. Feagan BG, Panaccione R, Sandborn WJ, et al. Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn's disease: results from the CHARM study. Gastroenterology. 2008; 135:1493–1499. PMID: 18848553.

8. Mao EJ, Hazlewood GS, Kaplan GG, Peyrin-Biroulet L, Ananthakrishnan AN. Systematic review with meta-analysis: comparative efficacy of immunosuppressants and biologics for reducing hospitalisation and surgery in Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther. 2017; 45:3–13. PMID: 27862107.

9. Szamosi T, Banai J, Lakatos L, et al. Early azathioprine/biological therapy is associated with decreased risk for first surgery and delays time to surgery but not reoperation in both smokers and nonsmokers with Crohn's disease, while smoking decreases the risk of colectomy in ulcerative colitis. Eur J Gastroenterol Hepatol. 2010; 22:872–879. PMID: 19648821.

10. Sakatani A, Fujiya M, Ito T, et al. Infliximab extends the duration until the first surgery in patients with Crohn's disease. Biomed Res Int. 2013; 2013:879491. PMID: 24371835.

11. Ma C, Beilman CL, Huang VW, et al. Anti-TNF therapy within 2 years of Crohn's disease diagnosis improves patient outcomes: a retrospective cohort study. Inflamm Bowel Dis. 2016; 22:870–879. PMID: 26818419.

12. Gonzalez-Lama Y, Suarez C, Gonzalez-Partida I, et al. Timing of thiopurine or anti-TNF initiation is associated with the risk of major abdominal surgery in Crohn's disease: a retrospective cohort study. J Crohns Colitis. 2016; 10:55–60. PMID: 26520164.

13. Kuenzig ME, Lee SM, Eksteen B, et al. Smoking influences the need for surgery in patients with the inflammatory bowel diseases: a systematic review and meta-analysis incorporating disease duration. BMC Gastroenterol. 2016; 16:143. PMID: 28003021.

14. Lichtenstein GR, Yan S, Bala M, Blank M, Sands BE. Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn's disease. Gastroenterology. 2005; 128:862–869. PMID: 15825070.

15. Cosnes J, Nion-Larmurier I, Beaugerie L, Afchain P, Tiret E, Gendre JP. Impact of the increasing use of immunosuppressants in Crohn's disease on the need for intestinal surgery. Gut. 2005; 54:237–241. PMID: 15647188.

16. Chatu S, Saxena S, Subramanian V, et al. The impact of timing and duration of thiopurine treatment on first intestinal resection in Crohn's disease: national UK population-based study 1989-2010. Am J Gastroenterol. 2014; 109:409–416. PMID: 24469612.

17. Panes J, Lopez-Sanroman A, Bermejo F, et al. Early azathioprine therapy is no more effective than placebo for newly diagnosed Crohn';s disease. Gastroenterology. 2013; 145:766–774.e1. PMID: 23770132.

18. Cosnes J, Bourrier A, Laharie D, et al. Early administration of azathioprine vs conventional management of Crohn's disease: a randomized controlled trial. Gastroenterology. 2013; 145:758–765.e2. PMID: 23644079.

19. Bemelman WA, Warusavitarne J, Sampietro GM, et al. ECCO-ESCP consensus on surgery for Crohn's disease. J Crohns Colitis. [published online ahead of print May 11, 2017]. DOI: 10.1093/ecco-jcc/jjx061.