The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Background and Aims To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®. Methods Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The ‘switch cohort’ [SC] comprised patients who made the switch from Remicade® to CT-P13, and the ‘non-switch’ cohort [NC] patients remained under Remicade®. Results A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2–6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05]. Conclusions Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe.

Impaired innate inflammatory response has a key role in the Crohn's disease (CD) pathogenesis. The aim of this study was to investigate the possible role of the TLR10-TLR1-TLR6 gene cluster in CD susceptibility. A total of 508 CD patients (284, cohort 1 and 224, cohort 2) and 576 controls were included. TLR10-TLR1-TLR6 cluster single-nucleotide polymorphisms genotyping, NOD2 mutations and TLR10 mRNA quantification were performed using TaqMan assays. Nucleotide-binding oligomerization domain containing 2 (NOD2) and Toll-like receptor (TLR) loci interaction was analyzed by logistic regression and multifactor-dimensionality reduction (MDR). Entropy-based analysis was used to interpret combination effects. One TLR10 haplotype (TLR10 GGGG ) was found associated with CD susceptibility in both cohorts, individuals with two copies had approximately twofold more risk of CD susceptibility than individuals having no copies (odds ratio ¼ 1.89, P-value ¼ 0.0002). No differences in the mRNA levels were observed among the genotypes. The strongest model for predicting CD risk according to the MDR analysis was a two-locus model including NOD2 mutations and TLR10 GGGG haplotype (P c o0.0001). The interaction gain attributed to the combination of both genes was negative (IG ¼ À2.36%), indicating redundancy or independent effects. Our results support association of the TLR10 gene with CD susceptibility. The effect of TLR10 would be independent of NOD2, suggesting different signaling pathways for both genes.

Background Post-marketing data are required to confirm the durability and the long-term benefit and safety of UST in CD in clinical practice. Our aims were: (1) to evaluate the retention rate of UST in CD patients and to identify predictive factors of UST discontinuation; (2) to assess UST short-term effectiveness; (3) to analyse the durability of the response to UST in the long-term; and (4) to evaluate the safety of UST in clinical practice. Methods Retrospective, multicentre study (&gt;60 centres). Patients with active CD [(Harvey–Bradshaw (HBI) &gt;4)] that received at least one dose of UST intravenously before July 2018 were included. Clinical activity plus biochemical parameters were assessed at every UST administration. Clinical remission was defined as HBI score ≤4, and clinical response as a decrease in HBI ≥3 points. Loss of efficacy was defined as reappearance of symptoms that led to intensify the treatment dose, add another medication to control CD, switching or surgery in patients with short-term remission. The retention rate of UST treatment and the cumulative incidence of loss of efficacy were evaluated by survival curves, and predictive factors were assessed by Cox-regression. The short-term response was evaluated at week 8 and after the induction (week 16). Factors associated with short-term remission were assessed by multivariate analysis. Adverse events were recorded. Data quality was assured by remote monitoring. Results 331 CD patients have been included up to date (Table 1). The incidence rate of UST discontinuation was 15% per patient-year of follow-up: 8%, 13% and 20% at 6, 12 and 18 months (Figure 1). Previous surgery was the only factor associated with a higher risk of UST discontinuation [Hazard ratio (HR) = 2.03, 95% confidence interval (CI) = 1.1–3.6]. Short-term efficacy is shown in Figure 2. Previous surgery (OR = 0.3, 95% CI = 0.2–0.6) and higher HBI score at baseline (OR = 0.8, 95% CI=0.8–0.9) were associated with an impaired response to UST at week 16. The cumulative incidence of loss of response was 32% per-patient-year of follow-up (Figure 3); A higher HBI score at baseline was associated with a higher risk of losing response (HR = 1.2, 95% CI = 1.1–1.3). Neither the concomitant treatment with immunosuppressants nor the number of previous biologics were associated with UST short- and long-term benefit. Thirty adverse events were reported in 25 (7%) patients (Table 2). Conclusion Sustain is the largest real clinical practice study of UST to treat CD patients with the longest follow-up reported to date. UST was demonstrated to be effective in real-world use in the short and long run. Safety was consistent with the known profile of UST.

BACKGROUND & AIMS: Q8Tools 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 Q9 vs A2;