Physical Activity Is Inversely Associated with Clinical Exacerbation in Patients with Crohn’s Disease in Remission: A Prospective Cohort Study

Introduction: Diet can impact the clinical course of Crohn’s disease (CD). However, the importance of food processing level is uncertain. We aimed to evaluate whether ultra-processed foods (UPFs) are associated with an increased risk of relapse among patients with CD in clinical remission. Methods: In this prospective cohort study, adult patients with CD in clinical remission were followed for 1 year or until clinical relapse, as assessed by the Harvey Bradshaw index. Dietary intake was assessed using a food frequency questionnaire and a dedicated validated processed food questionnaire to evaluate UPF consumption. Multivariable Cox proportional hazard models were used to estimate the adjusted hazard ratio of disease relapse according to high or low UPF consumption. Results: A total of 111 patients with CD (mean age 37.9 ± 14.0 years) in clinical remission were followed. Over a median period of 12 months [interquartile range, 8–12], 24 patients (21.6%) experienced clinical relapse. Fecal calprotectin levels were increased at the relapse visit compared to baseline (193.0 μg/g [114.0–807.0] and 79.0 μg/g [17.0–274.5], respectively, p = 0.002). A higher intake of UPFs was associated with an increased risk of CD relapse (HR = 3.86; 95% CI 1.30–11.47). Ultra-processed breads and pastries, as well as oils and spreads, were the UPF subgroups with the strongest positive associations (HR = 3.27; 95% CI 1.26–8.45 and HR = 2.76; 95% CI 1.02–7.45, respectively). Conclusion: UPF consumption is associated with an increased risk of relapse in patients with CD in remission. This study, along with future research, can contribute to establishing nutritional guidelines aimed at reducing UPF consumption in this population.

FMT may increase the proportion of people with active UC who achieve clinical and endoscopic remission. The evidence was very uncertain about whether use of FMT in people with active UC impacted the risk of serious adverse events or improvement in quality of life. The evidence was also very uncertain about the use of FMT for maintenance of remission in people with UC, as well as induction and maintenance of remission in people with CD, and no conclusive statements could be made in this regard. Further studies are needed to address the beneficial effects and safety profile of FMT in adults and children with active UC and CD, as well as its potential to promote longer-term maintenance of remission in UC and CD.

P0540 Assessment of Metabolic-Associated Liver Disease in Patients with Crohn’s Disease in Long-Term Remission

Whether all Crohn's disease (CD) patients should maintain long-term azathioprine treatment in combination with infliximab remains controversial. We analyzed the predictive factors of infliximab failure after azathioprine withdrawal. This was an observational study from a single referral center. All patients with luminal CD in remission who stopped azathioprine after receiving infliximab in combination with azathioprine for at least 6 months were studied. Cumulative probabilities of infliximab failure-free survival were estimated by the Kaplan-Meier method from the date of azathioprine withdrawal to the date of infliximab failure or last known follow-up. Infliximab failure was defined by: (i) disease flare requiring shortening of the dosing interval or increasing the infliximab dose to 10 mg/kg, or switching to adalimumab; (ii) acute or delayed hypersensitivity reactions leading to infliximab discontinuation; or (iii) CD-related surgery. At last known follow-up, 35 out of 48 (73%) patients were infliximab failure free. The survival probabilities were 85% (+/-5%) at 12 months and 41% (+/-18%) at both 24 and 32 months. Cox proportional-hazards regression identified three predictors of infliximab failure: infliximab-azathioprine exposure duration of < or = 811 days (hazard ratio (HR)=7.46, P=0.01), C-reactive protein > 5 mg/l (HR=4.79, P=0.008), and platelet count > 298 10(9)/l (HR=4.75, P=0.02). In CD in clinical remission under azathioprine-infliximab combination therapy, azathioprine withdrawal is associated with a high risk of relapse in patients with a duration of combination therapy of < 27 months and/or the presence of biological inflammation.

Fecal transplantation for treatment of inflammatory bowel disease

Fecal transplantation for treatment of inflammatory bowel disease.

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, and immune response modulation is the main treatment strategy to induce remission in active CD. Certolizumab pegol (CZP) is a tumor necrosis factor-alfa (TNF-α) inhibitor which regulates impaired immune response. The primary objectives were to evaluate the efficacy and safety of CZP for the induction of remission in CD. We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD group specialized register, trials registers and other sources from inception to 28 January 2019. Moreover, we contacted the pharmaceutical company that manufactures CZP. We included randomized controlled trials comparing CZP with placebo or no treatment in active CD patients. We used standard Cochrane methodological procedures. The main outcomes selected for GRADE analysis were clinical remission at week 8 (Crohn's Disease Activity Index [CDAI] ≤150), clinical response at week 8 (CDAI reduction ≥ 100 or clinical remission), and serious adverse events. The Mantel-Haenszel random-effects method was applied for the statistical analyses. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). Four studies involving 1485 participants with moderate to severe CD met the inclusion criteria and were used in the meta-analyses. All studies included active CD patients with CDAI ranging from 220 to 450. Most patients were adults over 18 years of age. One study was identified as high risk of bias due to a non-identical placebo while the other studies were judged to be at low risk of bias.CZP (100 mg to 400 mg every 2 to 4 weeks) was shown to be superior to placebo for achieving clinical remission at week 8 (RR 1.36, 95% CI 1.11 to 1.66; moderate certainty evidence). The raw numbers of participants achieving clinical remission at week 8 were 26.9% (225/835) and 19.8% (129/650) in the CZP and the placebo groups, respectively.CZP was shown to be superior to placebo for achieving clinical response at week 8 (RR 1.29, 95% CI 1.09 to 1.53; moderate certainty evidence). In raw numbers, clinical response at week 8 was achieved in 40.2% (336/835) and 30.9% (201/650) of participants in the CZP and the placebo groups, respectively.In raw numbers, serious adverse events were observed in 8.7% (73/835) and 6.2% (40/650) of participants in the CZP and the placebo groups, respectively (RR 1.35, 95% CI 0.93 to 1.97; moderate certainty evidence). Serious adverse events included worsening Crohn's disease, infections, and malignancy. Moderate certainty evidence suggests that CZP is effective for induction of clinical remission and clinical response in participants with active CD patients. It is uncertain whether the risk of serious adverse events differs between CZP and placebo as the 95% CI includes the possibility of a small decrease or doubling of events. Future studies are needed to evaluate the long-term efficacy and safety of CZP in CD patients.

Diet and clinical remission in patients with inflammatory bowel disease: A multicenter cross-sectional study.

Objectives: Patients with Crohn’s disease (CD) often report food hypersensitivities with gastrointestinal (GI) symptoms despite being in clinical remission. We aimed to identify the most frequent symptoms and dietary triggers in such patients, and also explored whether a strict elimination diet may reduce their GI symptoms.Methods: We assessed GI symptoms and dietary triggers in 16 patients with CD in clinical remission. Of these, 12 patients subsequently participated in a dietary intervention trial: two weeks on a habitual diet including wheat and dairy products followed by two weeks of a strict elimination diet. The severity of seven symptoms (overall symptoms, abdominal pain, bloating, abnormal feces, wind, fatigue, and musculoskeletal pain) was measured by using visual analog scales throughout the four weeks intervention period.Main results: The most common symptoms were abdominal pain, wind, bloating, odorous wind/feces, and diarrhea. Dairy and wheat products were reported as the most frequent dietary symptom triggers. All symptoms improved (p < .05) during the elimination diet period, especially in patients with small intestinal affection.Conclusion: Our exploratory study suggests that dietary interventions such as an elimination diet may reduce GI symptoms in patients with CD in remission.

Understanding the Role of PUFAs in Crohn’s Disease

There is no known cure for Crohn’s disease (CD), but a better understanding of the evidence base of both established treatments (such as enteral nutrition, corticosteroids, 5-aminosalicylates and immunosuppressive agents)...

Introduction: Crohn’s disease (CD) is a chronic inflammatory bowel disease characterized by a relapsing-remitting course with trans-mural inflammation of potentially any section of the digestive tract. Adalimumab (ADA) is a subcutaneously administered, recombinant, fully human, IgG1 monoclonal antibody that binds with high affinity and specificity to human TNF-alpha, thus modulating its biologic functions and its proinflammatory effects.Aims: To review the available data on ADA in CD for biological properties, efficacy, and safety.Methods:Electronic searches were conducted using the Pubmed and SCOPUS databases from the earliest records to April 2008. The search terms used were “adalimumab”, “anti-TNF”, “TNF-alpha”, “biologicals”, “inflammatory bowel disease”, and “Crohn’s disease”. Reference lists of all relevant articles were searched for further studies.Results:Available studies suggest that ADA has the potential to induce and maintain clinical response and remission in moderate-severe CD, both in anti-TNF-naïve patients and in subjects who lost their response and/or became intolerant to infliximab (IFX). ADA seems also effective in maintaining corticosteroid-free remission and obtaining complete fistula closure (although no specific randomized trials are available). No concomitant immunosuppressors seem to be necessary. Side effects appear similar to IFX, while site-injection reactions are frequent and specific. Data on immunogenicity and its clinical impact are uncertain.Conclusions:ADA appears to be effective in inducing and maintain clinical remission in CD, including patients not manageable with IFX. Successive clinical practice and further on going trials will confirm a positive role for ADA as a new anti-TNF treatment in CD. The impact on clinical management or on resources should be more studied.

Combined azithromycin and metronidazole therapy is effective in inducing remission in pediatric Crohn's disease

Children with Crohn's disease (CD) may report abdominal pain despite clinical remission, suggesting that functional abdominal pain (FAP) may be playing a role. The aim of this study was to explore the presence and impact of FAP in children with CD in remission. Children, aged 9 to 17 years, with CD were enrolled. Demographic information, the Pediatric Crohn's Disease Activity Index, and the Children's Depression Inventory were obtained. Disease remission was defined by physician global assessment, normal laboratories findings, absence of 3 or more stools a day, nocturnal stooling, bloody diarrhea, concurrent steroid therapy, strictures, or disease flare within 6 months. FAP was defined as patients with abdominal pain and CD remission. Rates of depression (Children's Depression Inventory >9) were compared. Of 307 children, 139 reported abdominal pain. Of this group, 18 of 139 (13%) children met the criteria for FAP. Despite clinical remission, 8 of 18 patients with CD having FAP were classified with active disease by Pediatric Crohn's Disease Activity Index. These patients had a higher rate of depression than patients with CD in remission with no abdominal pain (55.6% versus 29.9%; P = 0.03), similar to patients with abdominal pain from active CD (55.6% versus 44.8%; P = 0.62). A proportion of children with CD in remission have FAP. These children are at significant risk of depression. Future studies are needed to determine whether depression contributes to functional pain development or if pain itself leads to depression. Especially given that functional pain may exaggerate disease activity, clinicians caring for children with CD and FAP should consider evaluating for depressive disorders before escalating therapy.

Patients with Crohn's disease (CD) in clinical remission with elevated C-reactive protein (CRP) have been labeled "silent CD" and have increased 2-year hospitalization rates when compared with asymptomatic patients with no biochemical evidence of inflammation. The risk of cumulative bowel damage in patients with silent CD is unknown. Observational study of patients with CD prospectively followed in a tertiary referral natural history registry. Consecutive patients with CD in clinical remission (Harvey-Bradshaw Index ≤ 4) with good quality of life (short inflammatory bowel disease questionnaire score ≥ 50), and same day CRP measurement at first encounter, followed for a minimum of 4 years formed the study population. Disease trajectory was determined using change in Lémann Index as a measure of bowel damage. A total of 185 patients with CD (median age 42 years; 51.4% men) were included in the study. CRP elevation was observed in 43 (23%) patients (Silent CD cohort). Majority of them showed worsening disease trajectories based on change in Lémann Index when compared with asymptomatic patients with normal CRP (65% versus 36%, P < 0.0001). Multinomial logistic regression analysis demonstrated that elevated CRP was independently associated with 7-fold higher odds (odds ratio = 6.93, P < 0.0001) of having worse disease trajectories when compared with stable disease trajectories. Two-thirds of patients with CD in clinical remission, while demonstrating elevated CRP, will develop bowel damage over the ensuing years, despite feeling well. These patients with silent CD are an "at-risk" group who warrant further investigation to prevent development of disease-related complications.