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
1
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Background/Aims: Our study aimed to evaluate the long-term outcomes and risk factors for relapse after anti-tumor necrosis factor (TNF)-α cessation in inflammatory bowel disease (IBD) patients because they are not well established. Methods: A retrospective multicenter cohort study was conducted involving patients with Crohn’s disease (CD) or ulcerative colitis (UC) from 10 referral hospitals in Korea who discontinued firstline anti-TNF therapy after achieving clinical remission. Results: A total of 109 IBD patients (71 CD and 38 UC) with a median follow-up duration of 56 months were analyzed. The cumulative relapse rates at 1, 3, and 5 years were 11.3%, 46.7%, and 62.5% for CD patients and 28.9%, 45.3%, and 60.9% for UC patients. Multivariable Cox analysis revealed that discontinuation owing to the clinician’s decision was associated with lower risk of relapse (vs patient’s preference: hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04 to 0.48; p=0.002) and adalimumab use was associated with higher risk of relapse (vs infliximab: HR, 4.42; 95% CI, 1.24 to 17.74; p=0.022) in CD patients. Mucosal healing was associated with lower risk of relapse (vs nonmucosal healing: HR, 0.12; 95% CI, 0.02 to 0.83; p=0.031) in UC patients. Anti-TNF re-induction was provided to 52 patients, and a response was obtained in 50 patients. However, 25 of them discontinued retreatment owing to a loss of response (n=15), the patient’s preference (n=6), and other factors (n=4). Conclusions: More than 60% of IBD patients in remission under anti-TNF therapy relapsed within 5 years of treatment cessation. Anti-TNF re-induction was effective. However, half of the patients discontinued anti-TNF therapy, and 50% of these patients discontinued treatment owing to loss of response.
Abstract
Background/Aims: Our study aimed to evaluate the long-term outcomes and risk factors for relapse after anti-tumor necrosis factor (TNF)-α cessation in inflammatory bowel disease (IBD) patients because they are not well established. Methods: A retrospective multicenter cohort study was conducted involving patients with Crohn’s disease (CD) or ulcerative colitis (UC) from 10 referral hospitals in Korea who discontinued firstline anti-TNF therapy after achieving clinical remission. Results: A total of 109 IBD patients (71 CD and 38 UC) with a median follow-up duration of 56 months were analyzed. The cumulative relapse rates at 1, 3, and 5 years were 11.3%, 46.7%, and 62.5% for CD patients and 28.9%, 45.3%, and 60.9% for UC patients. Multivariable Cox analysis revealed that discontinuation owing to the clinician’s decision was associated with lower risk of relapse (vs patient’s preference: hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04 to 0.48; p=0.002) and adalimumab use was associated with higher risk of relapse (vs infliximab: HR, 4.42; 95% CI, 1.24 to 17.74; p=0.022) in CD patients. Mucosal healing was associated with lower risk of relapse (vs nonmucosal healing: HR, 0.12; 95% CI, 0.02 to 0.83; p=0.031) in UC patients. Anti-TNF re-induction was provided to 52 patients, and a response was obtained in 50 patients. However, 25 of them discontinued retreatment owing to a loss of response (n=15), the patient’s preference (n=6), and other factors (n=4). Conclusions: More than 60% of IBD patients in remission under anti-TNF therapy relapsed within 5 years of treatment cessation. Anti-TNF re-induction was effective. However, half of the patients discontinued anti-TNF therapy, and 50% of these patients discontinued treatment owing to loss of response.
참고문헌 (36)
- Ford AC, "Efficacy of biological therapies in inflammatory bowel disease : systematic review and meta-analysis", Am J Gastroenterol, 106, pp.644~659 (2011)
- Tomohiro Fukuda, "Current new challenges in the management of ulcerative colitis", Intestinal research, 17(1), pp.36~44 (2019), 대한장연구학회[DOI]
- Lichtenstein GR, "Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn’s disease", Gastroenterology, 128, pp.862~869 (2005)
- Louis E, "Maintenance of remission among patients with Crohn’s disease on antimetabolite therapy after infliximab therapy is stopped", Gastroenterology, 142, pp.63~70 (2012)
- Hong SN, "Risk of incident Mycobacterium tuberculosis infection in patients with inflammatory bowel disease : a nationwide populationbased study in South Korea", Aliment Pharmacol Ther, 45, pp.253~263 (2017)
- Kirchgesner J, "Risk of serious and opportunistic infections associated with treatment of inflammatory bowel diseases", Gastroenterology, 155, pp.337~346 (2018)
- Rahier JF, "The European (ECCO) Consensus on infection in IBD: what does it change for the clinician?", Gut, 58, pp.1313~1315 (2009)
- Long MD, "Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease", Gastroenterology, 143, pp.390~399 (2012)
- Mocci G, "Dermatological adverse reactions during anti-TNF treatments : focus on inflammatory bowel disease", J Crohns Colitis, 7, pp.769~779 (2013)
- van der Valk ME, "Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFα therapy : results from the COIN study", Gut, 63, pp.72~79 (2014)
- Ben-Horin S, "Discontinuation of biological treatments in inflammatory bowel disease : a concise pragmatic review", J Clin Gastroenterol, 52, pp.6~12 (2018)
- Casanova MJ, "Evolution after anti-TNF discontinuation in patients with inflammatory bowel disease : a multicenter long-term follow-up study", Am J Gastroenterol, 112, pp.120~131 (2017)
- Reenaers C, "Outcomes 7 years after infliximab withdrawal for patients with Crohn’s disease in sustained remission", Clin Gastroenterol Hepatol, 16, pp.234~243 (2018)
- Gisbert JP, "The risk of relapse after anti-TNF discontinuation in inflammatory bowel disease : systematic review and meta-analysis", Am J Gastroenterol, 111, pp.632~647 (2016)
- Papamichael K, "Long-term outcome of patients with Crohn’s disease who discontinued infliximab therapy upon clinical remission", Clin Gastroenterol Hepatol, 13, pp.1103~1110 (2015)
- Molander P, "Outcome after discontinuation of TNFα-blocking therapy in patients with inflammatory bowel disease in deep remission", Inflamm Bowel Dis, 20, pp.1021~1028 (2014)
- Clarke K, "Stopping immunomodulators and biologics in inflammatory bowel disease patients in remission", Inflamm Bowel Dis, 18, pp.174~179 (2012)
- Farkas K, "Predictors of relapse in patients with ulcerative colitis in remission after one-year of infliximab therapy", Scand J Gastroenterol, 48, pp.1394~1398 (2013)
- D’Haens GR, "The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn’s and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response?", Am J Gastroenterol, 106, pp.199~212 (2011)
- Dignass A, "The second European evidence-based consensus on the diagnosis and management of Crohn’s disease : current management", J Crohns Colitis, 4, pp.28~62 (2010)
- Dignass A, "Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2 : current management", J Crohns Colitis, 6, pp.991~1030 (2012)
- Hanauer SB, "Maintenance infliximab for Crohn’s disease : the ACCENT I randomised trial", Lancet, 359, pp.1541~1549 (2002)
- Colombel JF, "Infliximab, azathioprine, or combination therapy for Crohn’s disease", N Engl J Med, 362, pp.1383~1395 (2010)
- Colombel JF, "Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease : the CHARM trial", Gastroenterology, 132, pp.52~65 (2007)
- Roda G, "Loss of response to anti-TNFs : definition, epidemiology, and management", Clin Transl Gastroenterol, 7, pp.e135~ (2016)
- Kopylov U, "Therapeutic drug monitoring in inflammatory bowel disease", Ann Gastroenterol, 27, pp.304~312 (2014)
- Torres J, "Systematic review of effects of withdrawal of immunomodulators or biologic agents from patients with inflammatory bowel disease", Gastroenterology, 149, pp.1716~1730 (2015)
- Bortlik M, "Discontinuation of anti-tumor necrosis factor therapy in inflammatory bowel disease patients : a prospective observation", Scand J Gastroenterol, 51, pp.196~202 (2016)
- Steenholdt C, "Outcome after discontinuation of infliximab in patients with inflammatory bowel disease in clinical remission : an observational Danish single center study", Scand J Gastroenterol, 47, pp.518~527 (2012)
- Molnár T, "Predictors of relapse in patients with Crohn’s disease in remission after 1 year of biological therapy", Aliment Pharmacol Ther, 37, pp.225~233 (2013)
- Choon Jin Ooi, "Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn’s disease in Asia", Intestinal research, 17(3), pp.285~310 (2019), 대한장연구학회[DOI]
- Gisbert JP, "Systematic review : factors associated with relapse of inflammatory bowel disease after discontinuation of anti-TNF therapy", Aliment Pharmacol Ther, 42, pp.391~405 (2015)
- Ben-Horin S, "Review article : loss of response to anti-TNF treatments in Crohn’s disease", Aliment Pharmacol Ther, 33, pp.987~995 (2011)
- Casanova MJ, "Effectiveness and safety of the sequential use of a second and third anti-TNF agent in patients with inflammatory bowel disease : results from the Eneida Registry", Inflamm Bowel Dis, 26, pp.606~616 (2020)
- Song JH, "C-reactive protein reduction rate following initiation of anti-tumor necrosis factor α induction therapy predicts secondary loss of response in patients with Crohn’s disease", Scand J Gastroenterol, 54, pp.876~885 (2019)
- Gisbert JP, "Systematic review with meta-analysis : the efficacy of a second antiTNF in patients with inflammatory bowel disease whose previous anti-TNF treatment has failed", Aliment Pharmacol Ther, 41, pp.613~623 (2015)