The Relapse Rate of Inflammatory Bowel Disease (IBD) in Patients Who Discontinue Anti-TNF Therapy: A Systematic Review and Meta-Analysis
Abstract
Background: Inflammatory bowel disease (IBD) patients who cease anti-tumor necrosis factor (TNF) therapy are at risk of relapse, which is a matter of concern for the medical community. This study aimed to determine the relapse rate of IBD in patients who cease anti- TNF therapy.
Methods: A systematic search of international databases (Medline, Web of Sciences, Scopus, and EMBASE) was conducted until Mar 9th, 2022. The random effects model was used to calculate the IBD relapse rate, accompanied by a 95% confidence interval.
Results: The IBD relapse rate in patients who discontinued anti-TNF therapy was 44%. The pooled IBD-UC and IBD-CD relapse rate in patients who stopped anti-TNF therapy were 43% and 46%, respectively. The studies using infliximab (IFX) showed a pooled IBD relapse rate of 45%, and the IBD relapse rate in the IFX/ADA (Adalimumab) group was 42%. The IBD relapse rate for papers with treatment durations of less than or equal to 12 months was 51%, while for articles with treatment durations of more than 12 months, it was 30%.
Conclusion: This study emphasizes the need for careful evaluation and monitoring of IBD patients who cease anti-TNF therapy, as well as further investigation of alternative treatments for those who exhibit intolerance or inadequate response to anti-TNF therapy.
1. Ananthakrishnan AN, Kaplan GG, Ng SC (2020). Changing global epidemi-ology of inflammatory bowel diseases: sustaining health care delivery into the 21st century. Clin Gastroenterol Hepatol, 18 (6): 1252-60.
2. Chupin A, Perduca V, Meyer A, et al (2020). Systematic review with meta‐analysis: comparative risk of lymphoma with anti‐tumour necrosis factor agents and/or thiopurines in patients with inflammatory bowel disease. Aliment Pharmacol Ther, 52 (8): 1289-97.
3. Gomollón F, Dignass A, Annese V, et al. (2017). 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 1: diagnosis and medical management. J Crohns Colitis, 11 (1): 3-25.
4. Chen Y, Zhang G, Yang Y, et al (2023). The treatment of inflammatory bowel disease with monoclonal antibodies in Asia. Biomed Pharmacother, 157:114081.
5. Bots SJ, Kuin S, Ponsioen CY, et al (2019). Relapse rates and predictors for relapse in a real-life cohort of IBD patients after discontinuation of anti-TNF therapy. Scand J Gastroenterol, 54 (3): 281-8.
6. Torres J, Cravo M, Colombel JF (2016). Anti-TNF withdrawal in inflammatory bowel disease. GE Port J Gastroenterol, 23 (3): 153-61.
7. Stoker AM, Logghe L, van der Ende-van Loon MC, et al. (2023). Relapse rates after withdrawal versus maintaining biologic therapy in IBD patients with prolonged remission. Clin Exp Med, 23 (6): 2789-97.
8. Waugh A, Garg S, Matic K, et al (2010). Maintenance of clinical benefit in Crohn’s disease patients after discontinuation of infliximab: long‐term follow‐up of a single centre cohort. Aliment Pharmacol Ther, 32 (9): 1129-34.
9. Page MJ, McKenzie JE, Bossuyt PM, et al (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg, 88:105906.
10. Margulis AV, Pladevall M, Riera-Guardia N, et al (2014). Quality assessment of observational studies in a drug-safety systematic review, comparison of two tools: the Newcastle–Ottawa scale and the RTI item bank. Clin Epidemiol, 6: 359-68.
11. Moradi Y, Albatineh AN, Mahmoodi H, et al (2021). The relationship between depression and risk of metabolic syndrome: a meta‐analysis of observational studies. Clin Diabetes Endocrinol, 7 (1): 4.
12. Deeks JJ, Higgins JP, Altman DG, Group CSM (2019). Analysing data and undertaking meta‐analyses. Cochrane handbook for systematic reviews of interventions, pp: 241-84.
13. Deeks JJ, Macaskill P, Irwig L (2005). The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol, 58 (9): 882-93.
14. Brooks A, Sebastian S, Cross S, et al (2017). Outcome of elective withdrawal of anti-tumour necrosis factor-α therapy in patients with Crohn's disease in established remission. J Crohns Colitis, 11 (12): 1456-62.
15. Dart R, Griffin N, Taylor K, et al (2014). Reassessment of Crohn's disease treated with at least 12 months of anti-TNF therapy: how likely is treatment withdrawal? Frontline Gastroenterol, 5 (3): 176-82.
16. Song JH, Kang EA, Park SK, et al (2021). Long-term outcomes after the discontinuation of anti-tumor necrosis factor-α therapy in patients with inflammatory bowel disease under clinical remission: a Korean Association for the Study of Intestinal Disease Multicenter Study. Gut Liver, 15 (5): 752-62.
17. Molander P, Färkkilä M, Salminen K, et al (2014). Outcome after discontinuation of TNFα-blocking therapy in patients with inflammatory bowel disease in deep remission. Inflamm Bowel Dis, 20 (6): 1021-28.
18. Sahu P, Vuyyuru SK, Kante B, et al (2020). Relapse rate following withdrawal of anti-TNF therapy in patients with inflammatory bowel disease: a real-life cohort from northern India. Indian J Gastroenterol, 39 (4): 388-97.
19. Chauvin A, Le Thuaut A, Belhassan M, et al (2014). Infliximab as a bridge to remission maintained by antimetabolite therapy in Crohn's disease: a retrospective study. Dig Liver Dis, 46 (8): 695-700
20. Lu C, Waugh A, Bailey RJ, et al (2012). Crohn’s disease genotypes of patients in remission vs relapses after infliximab discontinuation. World J Gastroenterol, 18 (36): 5058-64.
21. Wynands J, Belbouab R, Candon S, et al (2008). 12-month follow-up after successful infliximab therapy in pediatric crohn disease. J Pediatr Gastroenterol Nutr, 46 (3): 293-98.
22. Louis E, Mary JY, Vernier–Massouille G, et al (2012). Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology, 142 (1): 63-70.e5; quiz e31.
23. Crombé V, Salleron J, Savoye G, et al (2011). Long-term outcome of treatment with infliximab in pediatric-onset Crohn's disease: a population-based study. Inflamm Bowel Dis, 17 (10): 2144-52.
24. Guidi L, Ratto C, Semeraro S, et al (2008). Combined therapy with infliximab and seton drainage for perianal fistulizing Crohn’s disease with anal endosonographic monitoring: a single-centre experience. Tech Coloproctol, 12 (2):111-7.
25. Domenech E, Hinojosa J, Nos P, et al (2005). Clinical evolution of luminal and perianal Crohn's disease after in-ducing remission with infliximab: how long should patients be treated? Ali-ment Pharmacol Ther, 22(11-12): 1107-13.
26. Bortlik M, Duricova D, Machkova N, et al (2016). Discontinuation of anti-tumor necrosis factor therapy in inflammatory bowel disease patients: a prospective observation. Scand J Gastroenterol, 51 (2): 196-202.
27. Steenholdt C, Molazahi A, Ainsworth MA, et al (2012). Outcome after discontinuation of infliximab in patients with inflammatory bowel disease in clinical remission: an observational Danish single center study. Scand J Gastroenterol, 47 (5): 518-27.
28. Dai C, Liu W-X, Jiang M, Sun M-J (2014). Mucosal healing did not predict sustained clinical remission in patients with IBD after discontinuation of one-year infliximab therapy. PLoS One, 9 (10): 110797.
29. Farkas K, Lakatos PL, Nagy F, et al (2013). Predictors of relapse in patients with ulcerative colitis in remission after one-year of infliximab therapy. Scand J Gastroenterol, 48 (12): 1394-98.
30. Molnár T, Lakatos PL, Farkas K, et al (2013). Predictors of relapse in patients with Crohn's disease in remission after 1 year of biological therapy. Aliment Pharmacol Ther, 37 (2): 225-33.
31. Gisbert JP, Marin AC, Chaparro M (2016). The risk of relapse after anti-TNF discontinuation in inflammatory bowel disease: systematic review and meta-analysis Am J Gastroenterol, 111(5): 632-47.
32. Fiocchi C, Danese S (2006). Etiopathogenesis of inflammatory bowel diseases. World J Gastroenterol, 12 (30): 4807-12.
33. Jostins L, Ripke S, Weersma RK, et al (2012). Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature, 491 (7422): 119-24.
34. Luppino I, Spagnuolo R, Marasco R, et al (2013). P. 02.11 Withdrawal of infliximab (Ifx) after achieving remission: outcome in a cohort of inflammatory bowel disease (Ibd) patients. Dig Liver Dis, 45:S100-S101.
35. Colombel JF, Sandborn WJ, Reinisch W, et al (2010). Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med, 362 (15): 1383-95.
36. Kilby K, Mathias H, Boisvenue L, et al (2019). Micronutrient absorption and related outcomes in people with inflammatory bowel disease: a review. Nutrients, 11 (6):1388.
37. Sands BE, Sandborn WJ, Panaccione R, et al (2019). Ustekinumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med, 381(13): 1201-1214.
38. Torres J, Boyapati RK, Kennedy NA, et al (2015). Systematic review of effects of withdrawal of immunomodulators or biologic agents from patients with inflammatory bowel disease. Gastroenterology, 149 (7): 1716-30.
39. Klaudia Farkas, Péter László Lakatos, Nagy F, et al (2013). Predictors of early relapse in patients with ulcerative colitis in remission after 1 year of infliximab therapy. Scand J Gastroenterol, 48 (12): 1394-98.
2. Chupin A, Perduca V, Meyer A, et al (2020). Systematic review with meta‐analysis: comparative risk of lymphoma with anti‐tumour necrosis factor agents and/or thiopurines in patients with inflammatory bowel disease. Aliment Pharmacol Ther, 52 (8): 1289-97.
3. Gomollón F, Dignass A, Annese V, et al. (2017). 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 1: diagnosis and medical management. J Crohns Colitis, 11 (1): 3-25.
4. Chen Y, Zhang G, Yang Y, et al (2023). The treatment of inflammatory bowel disease with monoclonal antibodies in Asia. Biomed Pharmacother, 157:114081.
5. Bots SJ, Kuin S, Ponsioen CY, et al (2019). Relapse rates and predictors for relapse in a real-life cohort of IBD patients after discontinuation of anti-TNF therapy. Scand J Gastroenterol, 54 (3): 281-8.
6. Torres J, Cravo M, Colombel JF (2016). Anti-TNF withdrawal in inflammatory bowel disease. GE Port J Gastroenterol, 23 (3): 153-61.
7. Stoker AM, Logghe L, van der Ende-van Loon MC, et al. (2023). Relapse rates after withdrawal versus maintaining biologic therapy in IBD patients with prolonged remission. Clin Exp Med, 23 (6): 2789-97.
8. Waugh A, Garg S, Matic K, et al (2010). Maintenance of clinical benefit in Crohn’s disease patients after discontinuation of infliximab: long‐term follow‐up of a single centre cohort. Aliment Pharmacol Ther, 32 (9): 1129-34.
9. Page MJ, McKenzie JE, Bossuyt PM, et al (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg, 88:105906.
10. Margulis AV, Pladevall M, Riera-Guardia N, et al (2014). Quality assessment of observational studies in a drug-safety systematic review, comparison of two tools: the Newcastle–Ottawa scale and the RTI item bank. Clin Epidemiol, 6: 359-68.
11. Moradi Y, Albatineh AN, Mahmoodi H, et al (2021). The relationship between depression and risk of metabolic syndrome: a meta‐analysis of observational studies. Clin Diabetes Endocrinol, 7 (1): 4.
12. Deeks JJ, Higgins JP, Altman DG, Group CSM (2019). Analysing data and undertaking meta‐analyses. Cochrane handbook for systematic reviews of interventions, pp: 241-84.
13. Deeks JJ, Macaskill P, Irwig L (2005). The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol, 58 (9): 882-93.
14. Brooks A, Sebastian S, Cross S, et al (2017). Outcome of elective withdrawal of anti-tumour necrosis factor-α therapy in patients with Crohn's disease in established remission. J Crohns Colitis, 11 (12): 1456-62.
15. Dart R, Griffin N, Taylor K, et al (2014). Reassessment of Crohn's disease treated with at least 12 months of anti-TNF therapy: how likely is treatment withdrawal? Frontline Gastroenterol, 5 (3): 176-82.
16. Song JH, Kang EA, Park SK, et al (2021). Long-term outcomes after the discontinuation of anti-tumor necrosis factor-α therapy in patients with inflammatory bowel disease under clinical remission: a Korean Association for the Study of Intestinal Disease Multicenter Study. Gut Liver, 15 (5): 752-62.
17. Molander P, Färkkilä M, Salminen K, et al (2014). Outcome after discontinuation of TNFα-blocking therapy in patients with inflammatory bowel disease in deep remission. Inflamm Bowel Dis, 20 (6): 1021-28.
18. Sahu P, Vuyyuru SK, Kante B, et al (2020). Relapse rate following withdrawal of anti-TNF therapy in patients with inflammatory bowel disease: a real-life cohort from northern India. Indian J Gastroenterol, 39 (4): 388-97.
19. Chauvin A, Le Thuaut A, Belhassan M, et al (2014). Infliximab as a bridge to remission maintained by antimetabolite therapy in Crohn's disease: a retrospective study. Dig Liver Dis, 46 (8): 695-700
20. Lu C, Waugh A, Bailey RJ, et al (2012). Crohn’s disease genotypes of patients in remission vs relapses after infliximab discontinuation. World J Gastroenterol, 18 (36): 5058-64.
21. Wynands J, Belbouab R, Candon S, et al (2008). 12-month follow-up after successful infliximab therapy in pediatric crohn disease. J Pediatr Gastroenterol Nutr, 46 (3): 293-98.
22. Louis E, Mary JY, Vernier–Massouille G, et al (2012). Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology, 142 (1): 63-70.e5; quiz e31.
23. Crombé V, Salleron J, Savoye G, et al (2011). Long-term outcome of treatment with infliximab in pediatric-onset Crohn's disease: a population-based study. Inflamm Bowel Dis, 17 (10): 2144-52.
24. Guidi L, Ratto C, Semeraro S, et al (2008). Combined therapy with infliximab and seton drainage for perianal fistulizing Crohn’s disease with anal endosonographic monitoring: a single-centre experience. Tech Coloproctol, 12 (2):111-7.
25. Domenech E, Hinojosa J, Nos P, et al (2005). Clinical evolution of luminal and perianal Crohn's disease after in-ducing remission with infliximab: how long should patients be treated? Ali-ment Pharmacol Ther, 22(11-12): 1107-13.
26. Bortlik M, Duricova D, Machkova N, et al (2016). Discontinuation of anti-tumor necrosis factor therapy in inflammatory bowel disease patients: a prospective observation. Scand J Gastroenterol, 51 (2): 196-202.
27. Steenholdt C, Molazahi A, Ainsworth MA, et al (2012). Outcome after discontinuation of infliximab in patients with inflammatory bowel disease in clinical remission: an observational Danish single center study. Scand J Gastroenterol, 47 (5): 518-27.
28. Dai C, Liu W-X, Jiang M, Sun M-J (2014). Mucosal healing did not predict sustained clinical remission in patients with IBD after discontinuation of one-year infliximab therapy. PLoS One, 9 (10): 110797.
29. Farkas K, Lakatos PL, Nagy F, et al (2013). Predictors of relapse in patients with ulcerative colitis in remission after one-year of infliximab therapy. Scand J Gastroenterol, 48 (12): 1394-98.
30. Molnár T, Lakatos PL, Farkas K, et al (2013). Predictors of relapse in patients with Crohn's disease in remission after 1 year of biological therapy. Aliment Pharmacol Ther, 37 (2): 225-33.
31. Gisbert JP, Marin AC, Chaparro M (2016). The risk of relapse after anti-TNF discontinuation in inflammatory bowel disease: systematic review and meta-analysis Am J Gastroenterol, 111(5): 632-47.
32. Fiocchi C, Danese S (2006). Etiopathogenesis of inflammatory bowel diseases. World J Gastroenterol, 12 (30): 4807-12.
33. Jostins L, Ripke S, Weersma RK, et al (2012). Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature, 491 (7422): 119-24.
34. Luppino I, Spagnuolo R, Marasco R, et al (2013). P. 02.11 Withdrawal of infliximab (Ifx) after achieving remission: outcome in a cohort of inflammatory bowel disease (Ibd) patients. Dig Liver Dis, 45:S100-S101.
35. Colombel JF, Sandborn WJ, Reinisch W, et al (2010). Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med, 362 (15): 1383-95.
36. Kilby K, Mathias H, Boisvenue L, et al (2019). Micronutrient absorption and related outcomes in people with inflammatory bowel disease: a review. Nutrients, 11 (6):1388.
37. Sands BE, Sandborn WJ, Panaccione R, et al (2019). Ustekinumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med, 381(13): 1201-1214.
38. Torres J, Boyapati RK, Kennedy NA, et al (2015). Systematic review of effects of withdrawal of immunomodulators or biologic agents from patients with inflammatory bowel disease. Gastroenterology, 149 (7): 1716-30.
39. Klaudia Farkas, Péter László Lakatos, Nagy F, et al (2013). Predictors of early relapse in patients with ulcerative colitis in remission after 1 year of infliximab therapy. Scand J Gastroenterol, 48 (12): 1394-98.
| Files | ||
| Issue | Vol 53 No 9 (2024) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v53i9.16452 | |
| Keywords | ||
| Inflammatory bowel diseases Treatment discontinuation Relapse Tumor necrosis factor Anti-TNF | ||
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How to Cite
1.
Ebrahimi F, Torkian S, Zare-Farashbandi E, Tamizifar B. The Relapse Rate of Inflammatory Bowel Disease (IBD) in Patients Who Discontinue Anti-TNF Therapy: A Systematic Review and Meta-Analysis. Iran J Public Health. 2024;53(9):1976-1991.
