Discontinuation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn's Disease:Individual Participant Data Meta-Analysis of 309 Patients from 12 Studies

BACKGROUND: The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk. METHODS: A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis. RESULTS: In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8-32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25-48%) and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%. CONCLUSIONS: This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup.</p

Discontinuation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn's Disease

The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk.A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual Participant Data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as (co)indication for start of anti-TNF therapy, >3 doses, and remission of luminal and pCD at anti-TNF discontinuation. Primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to retreatment and risk factors associated with relapse as assessed by Cox regression analysis.309 patients from 12 studies in 10 countries were included. Median duration of anti-TNF treatment was 14 months [IQR 5.8 - 32.5]. Most patients were treated for pCD without active luminal disease [89%], received first line anti-TNF therapy [87%] and continued immunomodulatory following anti-TNF discontinuation [78%]. Overall cumulative incidence of relapse was 36% [95% CI 25-48%] and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation. Risk factors for relapse included smoking [HR 1.5 (1.0, 2.1)] and history of proctitis [HR 1.7 (1.1, 2.5)]. Overall retreatment response rate was 82%.This IPD-MA, on predominantly patients with pCD without active luminal disease and first line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup

Global Hospitalization Trends for Crohn’s Disease and Ulcerative Colitis in the 21st Century: A Systematic Review With Temporal Analyses

The evolving epidemiologic patterns of inflammatory bowel disease (IBD) throughout the world, in conjunction with advances in therapeutic treatments, may influence hospitalization rates of IBD. We performed a systematic review with temporal analysis of hospitalization rates for IBD across the world in the 21st century. We systematically reviewed Medline and Embase for population-based studies reporting hospitalization rates for IBD, Crohn’s disease (CD), or ulcerative colitis (UC) in the 21st century. Log-linear models were used to calculate the average annual percentage change (AAPC) with associated 95% CIs. Random-effects meta-analysis pooled country-level AAPCs. Data were stratified by the epidemiologic stage of a region: compounding prevalence (stage 3) in North America, Western Europe, and Oceania vs acceleration of incidence (stage 2) in Asia, Eastern Europe, and Latin America vs emergence (stage 1) in developing countries. Hospitalization rates for a primary diagnosis of IBD were stable in countries in stage 3 (AAPC, −0.13%; 95% CI, −0.72 to 0.97), CD (AAPC, 0.20%; 95% CI, −1.78 to 2.17), and UC (AAPC, 0.02%; 95% CI, −0.91 to 0.94). In contrast, hospitalization rates for a primary diagnosis were increasing in countries in stage 2 for IBD (AAPC, 4.44%; 95% CI, 2.75–6.14), CD (AAPC, 8.34%; 95% CI, 4.38–12.29), and UC (AAPC, 3.90; 95% CI, 1.29–6.52). No population-based studies were available for developing regions in stage 1 (emergence). Hospitalization rates for IBD are stabilizing in countries in stage 3, whereas newly industrialized countries in stage 2 have rapidly increasing hospitalization rates, contributing to an increasing burden on global health care systems. [Display omitted