Intest Res.  2021 Jul;19(3):255-264. 10.5217/ir.2020.00029.

Correlation of serum levels of anti-tumor necrosis factor agents with perianal fistula healing in Crohn’s disease: a narrative review

Affiliations
  • 1Colorectal Surgery Unit, IBD Outpatient Clinics, Catholic University of Paraná (PUCPR), Curitiba, Brazil
  • 2IBD Outpatient Clinics, Hospital Nossa Senhora das Graças, Curitiba, Brazil

Abstract

With the overspread use of measurement of serum levels of anti-tumor necrosis factor (TNF) agents (therapeutic drug monitoring, TDM), new therapeutic strategies have been used in the management of Crohn’s disease (CD). Different targets are correlated with increased levels of circulating drugs. Recent evidence demonstrated that higher serum levels of anti-TNF agents may be associated to better outcomes in perianal fistulizing CD (PFCD). Overall, patients with healed fistulas had higher serum levels of infliximab and adalimumab as compared to those with active drainage. This was demonstrated in some cohort studies, in induction and maintenance, in adults and children with PFCD. In this narrative review, authors summarize current evidence on the use of serum level measurement of anti-TNF agents and its correlation with perianal fistula healing in CD patients. Data on the use of TDM in PFCD is discussed in detail. The retrospective design of the studies and the lack of objective parameters to measure fistula healing are the main limitations of published data. Prospective studies, with central reading of objective radiological parameters, such as pelvic magnetic resonance imaging scores, can improve the level of evidence on the possible advantages of TDM in perianal fistula in CD and are warranted.

Keyword

Crohn disease; Fistula; Tumor necrosis factor-alpha

Reference

1. Gomollón F, Dignass A, Annese V, et al. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 1: diagnosis and medical management. J Crohns Colitis. 2017; 11:3–25.
Article
2. Peyrin-Biroulet L, Loftus EV Jr, Colombel JF, Sandborn WJ. The natural history of adult Crohn’s disease in populationbased cohorts. Am J Gastroenterol. 2010; 105:289–297.
Article
3. Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2018; 390:2769–2778.
Article
4. Tang LY, Rawsthorne P, Bernstein CN. Are perineal and luminal fistulas associated in Crohn’s disease? A population-based study. Clin Gastroenterol Hepatol. 2006; 4:1130–1134.
Article
5. Tozer PJ, Burling D, Gupta A, Phillips RK, Hart AL. Review article: medical, surgical and radiological management of perianal Crohn’s fistulas. Aliment Pharmacol Ther. 2011; 33:5–22.
Article
6. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 1999; 340:1398–1405.
Article
7. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004; 350:876–885.
Article
8. Fu YM, Chen M, Liao AJ. A meta-analysis of adalimumab for fistula in Crohn’s disease. Gastroenterol Res Pract. 2017; 2017:1745692.
Article
9. Colombel JF, Schwartz DA, Sandborn WJ, et al. Adalimumab for the treatment of fistulas in patients with Crohn’s disease. Gut. 2009; 58:940–948.
Article
10. Castaño-Milla C, Chaparro M, Saro C, et al. Effectiveness of adalimumab in perianal fistulas in Crohn’s disease patients naive to anti-TNF therapy. J Clin Gastroenterol. 2015; 49:34–40.
Article
11. Schreiber S, Lawrance IC, Thomsen OØ, Hanauer SB, Bloomfield R, Sandborn WJ. Randomised clinical trial: certolizumab pegol for fistulas in Crohn’s disease: subgroup results from a placebo-controlled study. Aliment Pharmacol Ther. 2011; 33:185–193.
Article
12. Quaresma AB, Coy CSR, Damião AOMC, Kaplan GG, Kotze PG. Biological therapy penetration for inflammatory bowel disease in Latin America: current status and future challenges. Arq Gastroenterol. 2019; 56:318–322.
Article
13. Regueiro M, Mardini H. Treatment of perianal fistulizing Crohn’s disease with infliximab alone or as an adjunct to exam under anesthesia with seton placement. Inflamm Bowel Dis. 2003; 9:98–103.
Article
14. Maser EA, Villela R, Silverberg MS, Greenberg GR. Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn’s disease. Clin Gastroenterol Hepatol. 2006; 4:1248–1254.
Article
15. Ungar B, Levy I, Yavne Y, et al. Optimizing anti-TNF-α therapy: serum levels of infliximab and adalimumab are associated with mucosal healing in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2016; 14:550–557.
16. Chaparro M, Guerra I, Muñoz-Linares P, Gisbert JP. Systematic review: antibodies and anti-TNF-α levels in inflammatory bowel disease. Aliment Pharmacol Ther. 2012; 35:971–986.
Article
17. Billiet T, Cleynen I, Ballet V, et al. Prognostic factors for longterm infliximab treatment in Crohn’s disease patients: a 20- year single centre experience. Aliment Pharmacol Ther. 2016; 44:673–683.
Article
18. Feuerstein JD, Nguyen GC, Kupfer SS, Falck-Ytter Y, Singh S; American Gastroenterological Association Institute Clinical Guidelines Committee. American Gastroenterological Association Institute Guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology. 2017; 153:827–834.
Article
19. Davidov Y, Ungar B, Bar-Yoseph H, et al. Association of induction infliximab levels with clinical response in perianal Crohn’s disease. J Crohns Colitis. 2017; 11:549–555.
Article
20. Yarur AJ, Kanagala V, Stein DJ, et al. Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn’s disease. Aliment Pharmacol Ther. 2017; 45:933–940.
Article
21. Strik AS, Löwenberg M, Buskens CJ, et al. Higher anti-TNF serum levels are associated with perianal fistula closure in Crohn’s disease patients. Scand J Gastroenterol. 2019; 54:453–458.
Article
22. El-Matary W, Walters TD, Huynh HQ, et al. Higher postinduction infliximab serum trough levels are associated with healing of fistulizing perianal Crohn’s disease in children. Inflamm Bowel Dis. 2019; 25:150–155.
Article
23. Ruemmele FM, Rosh J, Faubion WA, et al. Efficacy of adalimumab for treatment of perianal fistula in children with moderately to severely active Crohn’s disease: results from IMAgINE 1 and IMAgINE 2. J Crohns Colitis. 2018; 12:1249–1254.
Article
24. Plevris N, Lyons M, Jenkinson PW, et al. Higher adalimumab drug levels during maintenance therapy for Crohn’s disease are associated with biologic remission. Inflamm Bowel Dis. 2019; 25:1036–1043.
Article
25. Denson LA, Curran M, McGovern DPB, et al. Challenges in IBD research: precision medicine. Inflamm Bowel Dis. 2019; 25(Suppl 2):S31–S39.
Article
26. Digby-Bell JL, Atreya R, Monteleone G, Powell N. Interrogating host immunity to predict treatment response in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2020; 17:9–20.
Article
27. Dreesen E, Bossuyt P, Mulleman D, Gils A, Pascual-Salcedo D. Practical recommendations for the use of therapeutic drug monitoring of biopharmaceuticals in inflammatory diseases. Clin Pharmacol. 2017; 9:101–111.
Article
28. Papamichael K, Rakowsky S, Rivera C, Cheifetz AS, Osterman MT. Association between serum infliximab trough concentrations during maintenance therapy and biochemical, endoscopic, and histologic remission in Crohn’s disease. Inflamm Bowel Dis. 2018; 24:2266–2271.
Article
29. Vande Casteele N, Khanna R, Levesque BG, et al. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn’s disease. Gut. 2015; 64:1539–1545.
Article
30. Roblin X, Marotte H, Rinaudo M, et al. Association between pharmacokinetics of adalimumab and mucosal healing in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2014; 12:80–84.
Article
31. Carlsen A, Omdal R, Leitao KØ, et al. Subtherapeutic concentrations of infliximab and adalimumab are associated with increased disease activity in Crohn’s disease. Therap Adv Gastroenterol. 2018; 11:1756284818759930.
Article
32. Vermeire S, Dreesen E, Papamichael K, Dubinsky MC. How, when, and for whom should we perform therapeutic drug monitoring? Clin Gastroenterol Hepatol. 2020; 18:1291–1299.
Article
33. Kelly OB, Donnell SO, Stempak JM, Steinhart AH, Silverberg MS. Therapeutic drug monitoring to guide infliximab dose adjustment is associated with better endoscopic outcomes than clinical decision making alone in active inflammatory bowel disease. Inflamm Bowel Dis. 2017; 23:1202–1209.
Article
34. Guidi L, Pugliese D, Tonucci TP, et al. Therapeutic drug monitoring is more cost-effective than a clinically based approach in the management of loss of response to infliximab in inflammatory bowel disease: an observational multicentre study. J Crohns Colitis. 2018; 12:1079–1088.
Article
35. Vande Casteele N, Ferrante M, Van Assche G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015; 148:1320–1329.
Article
36. D’Haens G, Vermeire S, Lambrecht G, et al. Increasing infliximab dose based on symptoms, biomarkers, and serum drug concentrations does not increase clinical, endoscopic, and corticosteroid-free remission in patients with active luminal Crohn’s disease. Gastroenterology. 2018; 154:1343–1351.
Article
37. Assa A, Matar M, Turner D, et al. Proactive monitoring of adalimumab trough concentration associated with increased clinical remission in children with Crohn’s disease compared with reactive monitoring. Gastroenterology. 2019; 157:985–996.
Article
38. Papamichael K, Vajravelu RK, Vaughn BP, Osterman MT, Cheifetz AS. Proactive infliximab monitoring following reactive testing is associated with better clinical outcomes than reactive testing alone in patients with inflammatory bowel disease. J Crohns Colitis. 2018; 12:804–810.
Article
39. Fernandes SR, Bernardo S, Simões C, et al. Proactive infliximab drug monitoring is superior to conventional management in inflammatory bowel disease. Inflamm Bowel Dis. 2020; 26:263–270.
Article
40. Dreesen E, D’Haens GR, Baert FJ, et al. Infliximab exposure predicts superior endoscopic outcomes in patients with active Crohn’s disease: pharmacokinetic-pharmacodynamic analysis of TAILORIX. J Crohns Colitis. 2018; 12(Supple 1):S063–S064.
41. Negoescu DM, Enns EA, Swanhorst B, et al. Proactive vs reactive therapeutic drug monitoring of infliximab in Crohn’s disease: a cost-effectiveness analysis in a simulated cohort. Inflamm Bowel Dis. 2020; 26:103–111.
Article
42. Pérez I, Fernández L, Sánchez-Ramón S, et al. Reliability evaluation of four different assays for therapeutic drug monitoring of infliximab levels. Therap Adv Gastroenterol. 2018; 11:1756284818783613.
Article
43. Vande Casteele N, Gils A. Pharmacokinetics of anti-TNF monoclonal antibodies in inflammatory bowel disease: adding value to current practice. J Clin Pharmacol. 2015; 55–Suppl 3:S39-S50.
Article
44. Vande Casteele N, Baert F, Bian S, et al. Subcutaneous absorption contributes to observed interindividual variability in adalimumab serum concentrations in Crohn’s disease: a prospective multicentre study. J Crohns Colitis. 2019; 13:1248–1256.
Article
45. Vermeire S, Gils A, Accossato P, Lula S, Marren A. Immunogenicity of biologics in inflammatory bowel disease. Therap Adv Gastroenterol. 2018; 11:1756283–X17750355.
Article
46. Van Stappen T, Vande Casteele N, Van Assche G, Ferrante M, Vermeire S, Gils A. Clinical relevance of detecting anti-infliximab antibodies with a drug-tolerant assay: post hoc analysis of the TAXIT trial. Gut. 2018; 67:818–826.
Article
47. Papamichael K, Cheifetz AS, Melmed GY, et al. Appropriate therapeutic drug monitoring of biologic agents for patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2019; 17:1655–1668.
Article
48. Yarur AJ, Jain A, Sussman DA, et al. The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: the ATLAS study. Gut. 2016; 65:249–255.
Article
49. Bemelman WA, Warusavitarne J, Sampietro GM, et al. ECCOESCP consensus on surgery for Crohn’s disease. J Crohns Colitis. 2018; 12:1–16.
Article
50. Kotze PG, Shen B, Lightner A, et al. Modern management of perianal fistulas in Crohn’s disease: future directions. Gut. 2018; 67:1181–1194.
Article
51. De Groof EJ, Sahami S, Lucas C, Ponsioen CY, Bemelman WA, Buskens CJ. Treatment of perianal fistula in Crohn’s disease: a systematic review and meta-analysis comparing seton drainage and anti-tumour necrosis factor treatment. Colorectal Dis. 2016; 18:667–675.
Article
52. Van Rijn KL, Lansdorp CA, Tielbeek JAW, et al. Evaluation of the modified van Assche index for assessing response to antiTNF therapy with MRI in perianal fistulizing Crohn’s disease. Clin Imaging. 2020; 59:179–187.
Article
53. Tandon P, Rhee GG, Schwartz D, McCurdy JD. Strategies to optimize anti-tumor necrosis factor therapy for perianal fistulizing Crohn’s disease: a systematic review. Dig Dis Sci. 2019; 64:3066–3077.
Article
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