Prediction of Relapse After Anti-Tumor Necrosis Factor Cessation in Crohn's Disease: Individual Participant Data Meta-analysis of 1317 Patients From 14 Studies.

BACKGROUND & AIMS: Tools for stratification of relapse risk of Crohn's disease (CD) after anti-tumor necrosis factor (TNF) therapy cessation are needed. We aimed to validate a previously developed prediction model from the diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressants (STORI) trial, and to develop an updated model. METHODS: Cohort studies were selected that reported on anti-TNF cessation in 30 or more CD patients in remission. Individual participant data were requested for luminal CD patients and anti-TNF treatment duration of 6 months or longer. The discriminative ability (concordance-statistic [C-statistic]) and calibration (agreement between observed and predicted risks) were explored for the STORI model. Next, an updated prognostic model was constructed, with performance assessment by cross-validation. RESULTS: This individual participant data meta-analysis included 1317 patients from 14 studies in 11 countries. Relapses after anti-TNF cessation occurred in 632 of 1317 patients after a median of 13 months. The pooled 1-year relapse rate was 38%. The STORI prediction model showed poor discriminative ability (C-statistic, 0.51). The updated model reached a moderate discriminative ability (C-statistic, 0.59), and included clinical symptoms at cessation (hazard ratio [HR], 2.2; 95% CI, 1.2-4), younger age at diagnosis (HR, 1.5 for A1 (age at diagnosis ≤16 years) vs A2 (age at diagnosis 17 - 40 years); 95% CI, 1.11-1.89), no concomitant immunosuppressants (HR, 1.4; 95% CI, 1.18-172), smoking (HR, 1.4; 95% CI, 1.15-1.67), second line anti-TNF (HR, 1.3; 95% CI, 1.01-1.69), upper gastrointestinal tract involvement (HR, 1.3 for L4 vs non-L4; 95% CI, 0.96-1.79), adalimumab (HR, 1.22 vs infliximab; 95% CI, 0.99-1.50), age at cessation (HR, 1.2 per 10 years younger; 95% CI, 1-1.33), C-reactive protein (HR, 1.04 per doubling; 95% CI, 1.00-1.08), and longer disease duration (HR, 1.07 per 5 years; 95% CI, 0.98-1.17). In subanalysis, the discriminative ability of the model improved by adding fecal calprotectin (C-statistic, 0.63). CONCLUSIONS: This updated prediction model showed a reasonable discriminative ability, exceeding the performance of a previously published model. It might be useful to guide clinical decisions on anti-TNF therapy cessation in CD patients after further validation.

Factors associated with depression in people with inflammatory bowel disease: The relationship between active disease and biases in neurocognitive processing.

BACKGROUND: Depression is common among people with inflammatory bowel disease (IBD), though the causes remain unclear. We conducted a cross-sectional study to investigate the role of emotional processing biases in contributing to depression among people with IBD. MATERIALS AND METHODS: One hundred and twenty outpatients with IBD were recruited and: (a) completed questionnaires to record: age, sex, social support, socioeconomic status, anxiety and depression (n = 104), (b) underwent assessments of biases in emotional recognition (n = 112), emotional memory and reinforcement learning (c) had recorded from clinical records: type of IBD, duration of IBD, IBD activity and (d) provided blood for high-sensitivity C-reactive protein levels (n = 99). KEY RESULTS: Sixty-eight participants had Crohn's disease and 49 had ulcerative colitis. Of these, 35 had active disease and 26 had depression. Those with depression were more likely to be female, lack social support, have active disease, be taking corticosteroids but not TNF-alpha inhibitors and exhibit less positive emotional recognition bias. On multivariable regression analysis, depression was associated independently with lack of social support (unstandardized regression coefficient (B) = -1.40, P = 0.02) and increased disease activity (B = 1.29, P = 0.03). Causal steps analysis was consistent with less positive emotional recognition bias partially mediating the effects of disease activity on depression. CONCLUSIONS AND INFERENCES: This is the first study to demonstrate links between disease activity and less positive biases in emotional recognition that could explain higher rates of depression among people with active IBD. Future prospective studies are required to confirm the effects of emotional processing biases in depression and allow stronger causal inferences to be drawn.

Nationwide linkage analysis in Scotland-Has mortality following hospital admission for Crohn's disease changed in the early 21st century?

BACKGROUND: National Scottish data were used to compare 3-year mortality in patients hospitalized for Crohn's disease (CD) between 1998-2000 and 2007-2009. METHODS: The linked Scottish Morbidity Records database was used to identify patients admitted with CD during two periods: Period 1 (1998-2000) and Period 2 (2007-2009). 3-year mortality and standardized mortality ratio (SMR) were determined and multivariable logistic regression analysis of associated factors was performed. Mortality was determined following four admission types: surgery-elective, surgery-emergency, medical-elective and medical-emergency. 3-year mortality was compared between study periods using age-standardized rates. RESULTS: The number of patients per 100,000 population hospitalized with CD per year was unchanged (15.7 [Period 1]; 14.4 [Period 2]). Overall crude and adjusted 3-year mortality rates were also unchanged (crude mortality 9.0%-9.1%, adjusted mortality odds ratio [OR]=0.87, 95% confidence interval [CI] 0.65-1.17; p=0.36). The adjusted 3-year mortality increased following elective surgery (Period 1: 1/303 [0.3%]; Period 2: 9/261 [3.4%]); OR=13.5 [CI 1.66-109.99]) and decreased following emergency medical admission (Period 1: 99/779 [12.7%]; Period 2:86/802 [10.7%]; OR=0.68 [CI 0.47-0.97]). Directly age-standardized mortality rates were similar (Period 1:338/10,000 person years [CI 282-394]; Period 2:333/10,000 person years [CI 276-390], p=0.2). On multivariable regression, age, deprivation status, comorbidity and the length of hospital stay were associated with mortality in both periods. High 3-year mortality was observed during both periods in patients between 50 and 64years (Period 1: 33/298 [11.1%, SMR=4.8 [CI 3.44-6.63], Period 2: 33/296 [11.1%, SMR=5.9 [4.14-8.22]) and over 65years(Period 1: 94/275 [34.2%, SMR=2.78 [CI 2.42-3.62], Period 2: 78/251 [31.1%, SMR=3.31 [2.64-4.11]). CONCLUSION: Nationwide linkage data demonstrate that overall 3-year mortality after hospitalization for CD is high, especially in patients over 50years, and has not altered between the time periods 1998-2000 and 2007-2009.