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OBJECTIVES OF THE STUDY There is little guidance regarding the impact of alcohol and cannabis on the clinical course of inflammatory bowel disease. The aim of this study was to assess the prevalence, sociodemographic characteristics and impact of alcohol and cannabis use on the clinical course of the disease. METHODS We performed an analysis of prospectively collected data within the Swiss Inflammatory Bowel Disease Cohort Study with yearly follow-ups and substance-specific questionnaires. We analyzed the prevalence of use, the profile of users at risk for addiction and the impact of alcohol and cannabis on the course of the disease. RESULTS We collected data of 2828 patients included between 2006 and 2018 and analyzed it according to their completion of specific surveys on alcohol and cannabis use. The prevalence of patient-reported active use was 41.3% for alcohol and 6% for cannabis. Heavy drinkers were over-represented among retired, married smokers receiving mostly aminosalicylates and less immunosuppression. In ulcerative colitis patients, low-to-moderate drinking was associated with less extensive disease. Cannabis users were often students with ileal Crohn's disease. CONCLUSION A significant proportion of patients with inflammatory bowel disease consume alcohol or cannabis. Heavy alcohol consumption is most likely in male smokers >50 years, whereas young men with ileal disease rather use cannabis.

Background/Aims In patients receiving ustekinumab (UST) for treatment of Crohn’s disease, there is no proven strategy to enhance or re-capture response. We assessed the utility of UST intravenous (IV) reinduction (~6 mg/kg) to achieve clinical, biochemical and endoscopic response or remission, in patients with partial or loss of response to UST maintenance therapy. Methods A multicentre, retrospective cohort study was performed. Adults who received an IV reinduction dose of UST for either partial response or secondary loss of response to UST were assessed. The primary outcome was clinical remission off corticosteroids (Harvey Bradshaw Index Results Sixty-five patients (median age 38 years, 54.7% women) underwent IV UST reinduction between January 2017 and April 2019. Most patients (88.3%) were already on escalated maintenance dosing of UST 90 mg subcutaneous every 4 weeks. Clinical outcomes were assessed at a median of 14 weeks (IQR: 12–19) post-reinduction. The primary outcome of clinical remission off corticosteroids with biochemical and/or endoscopic response was achieved in 31.0% (n = 18). Pre-reinduction UST concentrations were ≥1 μg/mL in 88.6% (mean 3.2 ± 2.0 μg/mL). No serious adverse events were reported. Conclusions UST IV reinduction can be effective in patients with Crohn’s disease with partial or loss of response to UST maintenance therapy. Further studies evaluating this strategy are warranted.

Background Vedolizumab (VDZ), a humanised monoclonal antibody against a4ß7‐integrin, has shown efficacy in inflammatory bowel disease (IBD). It is of importance to assess the mid‐to long‐term efficacy of VDZ using real‐life data. Objective Our study aimed to determine the efficacy of VDZ in patients with IBD with and without prior exposure to anti‐tumour necrosis factor (TNF) treatments in a real‐life setting. Furthermore, we investigated confounding factors influencing the remission to VDZ. Methods Patients participating in the Swiss IBD Cohort Study were included in this study. Remission was defined as calprotectin less than 200 mg/kg stool and/or mucosal healing determined by endoscopy. End points were determined between Months 4 and 8 (T1) and between Months 12 and 16 (T2) after VDZ induction. Results Remission was reported in 50.5% (110/218) of patients in T1 (48.7% Crohn's disease [CD] and 52.5% ulcerative colitis [UC]) and 46.8% (102/218) in T2 (47% CD and 46.5% UC). In UC patients, a significantly higher remission rate was achieved in T2 among anti‐TNF‐naive patients (57.7%) compared to anti‐TNF‐experienced patients (34.7%; p = 0.02; odds ratio = 0.39, 95% confidence interval: 0.17–0.87). In patients with CD, no difference could be seen in either evaluation interval. Multivariable analysis showed that disease duration significantly influenced remission rates among UC patients. A late response to VDZ therapy with an achievement of remission in T2 was seen in a fifth of all patients (CD: 21.7%, UC: 20.8%). VDZ treatment was stopped in a third of all patients (31.8%) due to nonresponse, adverse events or aggravation of extra‐intestinal manifestations. Conclusion In a real‐life national cohort setting, VDZ induced remission in more than half of IBD patients. Previous treatment with anti‐TNF agents was associated with a significant lower efficacy of VDZ in UC but not in CD patients.

Background: Patients with inflammatory bowel disease (IBD) have a higher risk of infection and are frequently not up to date with their immunizations. Objectives: This study aims to review vaccination status and evaluate whether age, disease type, or treatment regimen could predict the absence of seroprotection against selected vaccine-preventable infection in adults with IBD. Methods: Cross-sectional study using questionnaire, immunization records review, and assessment of tetanus-specific, varicella-specific, and measles-specific immunoglobulin G concentrations. ClinicalTrials.gov: NCT01908283. Results: Among the 306 adults assessed (median age 42.7 years old, 70% with Crohn’s disease, 78% receiving immunosuppressive treatment), only 33% had an immunization record available. Absence of seroprotection against tetanus (6%) was associated with increasing age and absence of booster dose; absence of seroprotection against varicella (1%) or measles (3%) was exclusively observed in younger patients with Crohn’s disease. There was no statistically significant difference in immunoglobulin concentrations among treatment groups. Although vaccinations are strongly recommended in IBD patients, the frequencies of participants with at least 1 dose of vaccine recorded were low for nearly all antigens: tetanus 94%, diphtheria 87%, pertussis 54%, poliovirus 22%, measles-mumps-rubella 47%, varicella-zoster 0%, Streptococcus pneumoniae 5%, Neisseria meningitidis 12%, hepatitis A 41%, hepatitis B 48%, human papillomavirus 5%, and tick-borne encephalitis 6%. Conclusions: Although many guidelines recommend the vaccination of IBD patients, disease prevention through immunization is still often overlooked, including in Switzerland, increasing their risk of vaccine-preventable diseases. Serological testing should be standardized to monitor patients’ protection during follow-up as immunity may wane faster in this population.

Background: Treatment of Crohn’s disease (CD) patients is complex as therapy choices depend on a variety of factors, such as location and severity of inflammation, disease behavior (inflammatory, stricturing or penetrating) but also comorbidities, extra-intestinal manifestations, the patient’s age, and previous therapies. Subsequently, the choice of treatment should be tailored to the individual patient. Summary: This article gives the reader therapy algorithms as a guide through different CD scenarios to support the physician’s decision making. New compounds introduced in CD therapy in recent years justify such an update on standard approaches. Ustekinumab and vedolizumab and their positions within the treatment options are discussed. Fistulizing perianal disease and postoperative medical prophylaxis are depicted in separate chapters with own algorithms. Key Messages: In recent years, a variety of new drugs became available to treat patients with CD – especially those who are antitumor necrosis factor (TNF) experienced with ongoing inflammation. The definitive role of vedolizumab and ustekinumab is not yet fully clarified. However, with the advantage of good safety profiles over TNF-inhibitors, these drugs will be more frequently used in the near future, also as first-line biologicals, compared to TNF-inhibitors. Concerning treatment of fistulizing disease, the knowledge of the exact anatomy of the fistula is of major importance. An interdisciplinary discussion involving gastroenterologists, surgeons, and in some cases gynecologists may help to optimize the treatment plan. Regarding the postsurgical setting in CD patients, according to the very recent Cochrane Network meta-analysis, mesalazine should be at least positioned equivalent to thiopurines and TNF-inhibitors, as shown in our algorithm.

Background: Anti-tumour necrosis factor-alpha (anti-TNF) antagonists have been the mainstay in the treatment of inflammatory bowel diseases (IBDs) for over 20 years. Summary: This review article aimed to provide an update on recent advances in TNF antagonist therapy for IBDs. Key Messages: Their position in the treatment algorithm has evolved to “rapid step-up therapy” or “top-down therapy” according to disease severity and patients’ characteristics. Limitations of anti-TNF antagonists include loss of response in up to 30–50% of patients with or without the development of antibodies. Therapeutic drug monitoring should provide a tailored, personalized approach to this scenario. Recently, biosimilar agents have been approved for IBDs and are considered equivalent in efficacy to the originator.

Background and aims: Anxiety and depression are prevalent in patients with inflammatory bowel diseases (IBD), especially during IBD flares. IBD therapies can profoundly affect the mood of patients with IBD. We aimed to determine the long-term impact of anti-tumor necrosis factor (anti-TNF) and immunomodulators (IM) on anxiety and depressive symptoms in IBD patients. Methods: We compared three treatment groups with IM only (group A), anti-TNF ± IM (group B) and no such therapy (group C). Patients completed the hospital anxiety and depression scale (HADS) at 1 year, 3 years, and 5 years after start of treatment. Results: In total, 581 patients with IBD (42.9% Crohn’s disease, 57.1% ulcerative colitis/IBD unclassified) participated in this study. Effects of treatment were analyzed in a mixed effects model, with and without correction for confounders. Compared with group C, group B showed a significant treatment-related improvement in both anxiety and depressive symptoms within the first 2.5 years and also thereafter. Group A showed a significant long-term improvement of anxiety and both short-term and long-term improvement in depressive symptoms. The significance of these results was maintained after correction for confounders, including corticosteroid treatment. Additionally, both groups A and B showed a significant decrease in disease activity in the first 2.5 years after start of treatment and also thereafter. Anti-TNF and IM treatment were associated with a similarly significant decrease in anxiety and depressive symptoms over an observation period of up to 5 years. Conclusion: Besides a clear benefit for disease activity, anti-TNF and IM apparently improve the mood of patients with IBD.

Background: Long-standing ulcerative colitis has been associated with an increased risk of colorectal cancer (CRC). Current guidelines recommend endoscopic CRC screening after 8 years of disease duration. The objectives of our study were to assess the adherence to recommendations and the quality of endoscopic procedure in long-standing ulcerative colitis. Methods: This is a retrospective cohort study. We selected patients included in the Swiss IBD cohort with a disease duration of ≥8 years and an extension above the rectosigmoid junction. The complementary medical chart review focused on endoscopy and associated histological reports in 8 Swiss centers. Descriptive analyses focused on patients and their colonoscopies. Results: 309 colonoscopies were conducted among 116 patients with the following characteristics: women 47%, mean age at diagnosis 31 years, and pancolitis disease extent in 65.5% of cases; 38.8% of patients had a first screening colonoscopy 10 years. Cecal intubation was performed in 94.5% of cases, and bowel preparation was good to excellent in 61.5% of endoscopies. Chromoendoscopy was used in 7.4% of cases, and the mean withdrawal time was 16.4 min. Dysplasia was found in 6.2% of cases. Conclusion: Despite current international recommendations, a significant number of patients did not receive a proper endoscopic surveillance. An increased use of chromoendoscopy, monitoring of withdrawal time, and appropriate bowel preparation would increase the quality of CRC screening. The adherence to screening guidelines and endoscopic quality should be promoted and standardized.

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P, Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.

Primary varicella zoster virus [VZV] infection results in varicella [chickenpox] and its reactivation results in herpes zoster [HZ; shingles]. Patients with inflammatory bowel disease [IBD] are susceptible to complications of primary VZV infection and have an increased risk of HZ. Concerns of VZV and HZ infection in the IBD population have been highlighted by the emergence of JAK inhibitors and their safety profile in this patient population, as with tofacitinib for the treatment of ulcerative colitis [UC]. The current pipeline of emerging therapies includes novel molecules targeting multiple pathways, including JAK/signal transducer and cytokine signalling pathways, such as JAK/STAT. Hence VZV and HZ will be increasingly relevant for gastroenterologists treating IBD patients in light of these emerging therapies. This review will focus on the epidemiology, disease course, prevention, and management of these two distinct infections in patients with IBD.

Background Evidence for second-line therapy in patients with microscopic colitis [MC] failing budesonide is scarce, although anti-tumour necrosis factors [anti-TNFs], methotrexate and azathioprine have been reported to be effective in small cohort studies. Vedolizumab, a monoclonal antibody targeting α4β7-integrin, prevents homing of T-cells to the gut. We evaluated clinical remission with vedolizumab in budesonide-refractory MC patients. Methods We solicited gastroenterologists in Europe and Canada for cases of MC treated with vedolizumab. Vedolizumab 300 mg IV was administered at weeks 0, 2 and 6, and then every 8 weeks. Clinical remission and histological remission were defined as less than three stools per day and normalization of histology, respectively, after induction treatment. Results Eleven cases were retrieved (nine females, lymphocytic colitis [LC] n = 5, collagenous colitis [CC] n = 6). Median [interquartile range] disease duration at vedolizumab initiation was 51 [29-70] months. Nine of 11 patients had failed one immunosuppressant and ten of 11 at least one anti-TNF agent. After three infusions of vedolizumab, clinical remission was observed in 5/11 patients [two LC and three CC] of whom three remained well with maintenance therapy [median duration of 13 months]. Biopsies were obtained from 9/11 patients. Histological remission was observed in 3/4 patients with clinical remission [2/3 CC, 1/1 LC] and 0/5 patients without clinical improvement. Conclusion In a series of highly refractory MC patients, vedolizumab induced clinical remission in 5/11 subjects, of whom 75% showed normalized histology. Larger randomized trials are needed to assess the efficacy of vedolizumab in patients with MC.

Background Long-term outcome of ustekinumab in Crohn's disease (CD) has not been evaluated. Aim To evaluate the long-term efficacy and safety of ustekinumab and identify the predictive factors of ustekinumab failure-free persistence in a cohort of anti-TNF refractory CD patients. Methods We performed a retrospective multicentre cohort study including all consecutive CD patients who began subcutaneous ustekinumab and presented a clinical response (defined as a significant improvement of CD-related clinical symptoms assessed by the patient's physician leading to continued ustekinumab) during the first year of treatment. Primary outcome was treatment failure defined as withdrawal of treatment due to loss of response, intolerance or need for surgery. Results Eighty-eight of the 122 (72%) CD patients beginning ustekinumab from March 2011 to December 2014, responded to ustekinumab and were followed up until November 2016. Median time on ustekinumab was 26.6 (13.4-34.4) months. Forty-seven patients (54%) continued ustekinumab with a clinical response and 38 (43%) stopped treatment (32 for failure, five for remission and one for pregnancy). Endoscopic response was observed in 82% of patients with endoscopic evaluation and mucosal healing in 39%. Ustekinumab failure-free persistence rates were 78% at 12 months, 66% at 24 months and 55% at 36 months. No predictive factor of ustekinumab failure-free persistence was identified. One severe adverse event was observed (anal adenocarcinoma). Conclusion In this cohort of refractory CD patients receiving long-term ustekinumab therapy, more than 50% of patients continued ustekinumab treatment with no loss of response, intolerance or surgery and with a good safety profile.

Background: Long-term data of certolizumab pegol (CZP) in Crohn's disease (CD) from pivotal registry trials are limited. We therefore aimed to evaluate the long-term efficacy of CZP in clinical practice in Switzerland. Methods: In the First Approved Certolizumab Therapeutic Experience in Switzerland-III phase IV multicenter cohort, patients receiving CZP were prospectively included all over Switzerland in (non-) academic hospitals and private practice. Results: We included 104 CD patients (52 male; only 22.1% anti-tumor necrosis factor (TNF) naïve, CZP as third anti-TNF agent in 46.2%) with follow-up time between 6 weeks up to 5 years. During treatment with CZP, we observed a significant decrease of the Harvey Bradshaw Index from a median of 7 at baseline (interquartile range 4-11) to 4, 5, 4, 3, 3, and 2 at weeks 6, 26, 52, 78, 104, and 156, respectively. While anti-TNF naïve patients showed a significantly better response at the end of induction, during CZP maintenance therapy response was similar as compared to anti-TNF experienced patients as well as between patients with a short (0-5 years) vs. long duration of disease (>5 years). Conclusions: CZP is an effective long-term treatment option, including CD patients with long disease duration and prior treatment with 1 or 2 anti-TNF agents.

Background Environmental factors, including sleep disturbances, have been associated with the risk of flare in inflammatory bowel disease (IBD). Symptoms, treatment side effects and pro-inflammatory status have been shown to have an effect on sleep quality and duration. Previous studies showed that around 44% of IBD patients suffer from sleep disorders. We aimed at determining the prevalence of sleep disturbances in IBD patients, as compared with normal controls, and factors associated with disturbances. Methods We conducted a cross-sectional study on adult patients included in the Swiss IBD cohort study. We excluded pregnant women and night workers. We used the HypnoLaus cohort as a control population. Demographics, clinical, treatments, SF-36 and IBDQ (bowel, emotional, social and systemic sub-scores) quality of life data were extracted from the SIBDCS. We sent patients a questionnaire comprising the Pittsburgh Sleep Quality Index (PSQI), Epworth score (ESS), and Restless Leg Syndrome (RLS) Score. We assessed differences regarding those scores between IBD and controls. We performed logistic regression analyses to evaluate factors associated with sleep disturbances in the IBD population. Results A total of 1139 patients answered to the questionnaire: 613 CD, 526 UC, 47% males, mean (SD) age: 50(15) years, median (IQR) disease duration: 15 (15) years. One out of five patients had extraintestinal manifestations (EIM). Forty-one percent were receiving biologic treatment (UC: 27.6%, CD: 53.0%). We found 906 age-sex-BMI matched controls who answered the PSQI, ESS and RLS. A significantly higher proportion of IBD patients had impaired sleep quality (PSQI) as compared with the control population (61.3% vs. 33.9%; p < .001). The proportion of IBD patients with ESS sleep deficiency (incl. daytime sleepness) was significantly higher as compared with controls (32.5% vs. 23.4%; p < .001). We also found a higher prevalence of RLS in IBD than in controls (27.8% vs. 13.0%; p < .001). Factors associated with impaired sleep quality were female gender (OR=1.37; p = .048), IBDQ bowel (OR=1.03; p = .033) and IBDQ systemic (OR=0.83; p < .001). ESS sleep deficiency was associated with IBDQ emotional (OR=1.02, p = .050) and social (OR=0.95; p = .046). RLS was associated with increased age (OR=1.02, p < .001), being a smoker (OR=1.54; p = 0.035), prior steroid use (OR=2.17, p = .001) and IBDQ emotional (OR=0.95, p = .005). Conclusion Sleep disturbances are highly prevalent in IBD patients compared with the control population. In IBD, sleep disturbances were associated with IBD-specific quality of life, but not with disease activity and EIM. Future studies should address whether early detection and active management of sleep disorders might influence disease control and long-term outcomes.

Background This study aimed to evaluate the clinical outcomes for adults diagnosed with Crohn’s disease (CD) who started biologic treatments within 2 years of diagnosis (early initiation) compared with those who started biologics >2 years after diagnosis or who did not receive any biologic treatment during the period of observation (late/no biologic initiation). Methods We conducted a retrospective analysis using 10 years of follow-up data from patients included in a national cohort study. We used propensity score methods to match patients in the early vs. late/no biologic initiation groups based on key baseline patient and clinical characteristics. Kaplan–Meier time-to-event models were used to evaluate the risks of intestinal resection surgery, fistula, stricture, and disease flares for each group. In addition, a subgroup analysis was performed stratifying patients known to have initiated biologic treatments into early (≤2 years after diagnosis) vs. late (>2 years after diagnosis) initiation groups. Results In total, 411 patients were matched in the early initiation (n = 230) vs. late/no initiation (n = 181) groups. Two years after diagnosis, early biologic initiators had a 12% lower probability of intestinal resection surgery, a 9% higher probability of disease flares and fistulae, and a 5% higher probability of strictures compared with the late/no biologic initiators (Figure 1). After 10 years, the overall difference in the cumulative probability for each event were not statistically significant between the two groups. In the subgroup analysis, patients who initiated biologics early had a lower overall probability of stricture (p < 0.01), disease flares (p < 0.01), and intestinal resection surgery (p = 0.72), and a higher probability of fistula (p = 0.74) 10 years after diagnosis when compared with the group of patients who initiated biologics late. Conclusion This study found no significant differences in the long-term cumulative probabilities of intestinal resection surgery, fistula, stricture, and disease flares amongst CD patients who initiated biologic treatment early compared with similar patients who initiated biologic therapy late or who had not started any biologic treatments. However, in a subgroup of patients known to receive biologic treatments, early initiation was associated with significantly lower overall risks of strictures and disease flares. These results highlighted the need for more individualised care in CD in order to target aggressive treatment approaches to patients who show early signs of a complicated disease course.

Background: Loss of response is frequently encountered in patients with inflammatory bowel disease (IBD) treated with antitumor necrosis factor (TNF) agents. Therapeutic drug monitoring (TDM) and antidrug antibody measurement are increasingly used in this setting. Methods: To establish a consensus on the use of TDM in the context of loss of response to anti-TNFs, we performed a vote using a Delphi-style process followed by an expert panel discussion among 8 IBD specialists practicing in Switzerland, Europe. Statements were rated on an even Likert-scale ranging from 1 (strong disagreement) to 4 (strong agreement), based on expert opinion and the available literature. Results: The experts agreed on the following statements: (i) loss of response is associated with inadequate drug levels in both Crohn’s disease and ulcerative colitis; (ii) best timepoint for measuring drug levels is prior to the next application (= trough levels) with different thresholds for anti-TNF agents (infliximab 5 μg/mL, adalimumab 8 μg/mL, certolizumab pegol 10 μg/mL); (iii) antidrug antibodies are predictive for loss of response; and (iv) antidrug-antibody titers and drug trough levels are key determinants in the treatment algorithm. Data about non-anti-TNF biologics were considered too limited to propose recommendations. Conclusion: A Delphi-style consensus among 8 IBD experts shows that TDM and measurement of antidrug-antibody titers are useful in the context of loss of response to anti-TNF. Optimal cutoff levels depend on the type of anti-TNF. These values are critical in the decision making process. More studies are needed to address the value of such measurements for non-anti-TNF biologics.

The relevance of azathioprine and 6-mercaptopurine therapy in inflammatory bowel disease, Crohn's disease, and ulcerative colitis, has been challenged in recent publications. In this article, a panel of experts gives advice, based on the relevant literature, on indications and practical use of azathioprine/6-mercaptopurine, prevention, and management of drug adverse reactions and special situations such as vaccination, pregnancy, and lactation.

Background & Aims Inflammatory bowel disease (IBD) scoring systems combine patient-reported data with physicians’ observations to determine patient outcomes, but these systems are believed to have limitations. We used real-world data from a large IBD cohort in Switzerland to compare results between patients and healthcare professionals from scoring systems for Crohn’s disease (CD) and ulcerative colitis (UC). Methods We collected data from the Swiss IBD cohort, beginning in 2006, using 2453 reports for 1385 patients (52% female, 58% with CD). During office visits, physicians asked patients about signs and symptoms and recorded their answers (health care professional-reported outcomes). On a later date, patients received a questionnaire at home (independently of the medical visit), complete it, and sent it back to the data center. Patients also completed the short form 36 and IBD quality of life (QoL) questionnaires. We calculated Cohen’s kappa (κ) statistics to assess the level of agreement in scores between patients and health care professionals (Δt between reports collected less than 2 months apart). We used Spearman correlation coefficients (ρ) to compare general well-being (GWB) and QoL scores determined by patients vs health care professionals. Our primary aim was to investigate the overall and individual level of agreement on signs and symptoms reported by health care professionals vs patients. Results The best level of agreement (although moderate) was observed for number of stools last week in patients with CD (κ = 0.47), and nocturnal diarrhea in patients with UC (κ = 0.52). Agreement was low on level of abdominal pain (κ = 0.31 for patients with CD and κ = 0.37 for patients with UC) and GWB (κ = 0.23 for patients with CD and κ = 0.26 for patients with UC). Patients reported less severe abdominal pain and worse GWB (CD) or better GWB (UC) than that determined by health care professionals. Patient self-rated GWB correlated with IBD quality of life (ρ = 0.68 for patients with CD and ρ = 0.70 for patients with UC) and SF-36 physical scores (ρ = 0.55 for patients with CD and ρ = 0.60 for patients with UC); there was no correlation between health care professional-rated GWB and QoL. Conclusions In a comparison of patient vs health care provider-reported outcomes in a Swiss IBD cohort, we found that health care professionals seem to misinterpret patients’ complaints. Patients self-rated GWB correlated with QoL scores, indicating that reporting GWB in a single question is possible and relevant, but can vary based on how the data are collected.

Crohn's disease (CD) evolution is characterized by increasing proportions of patients developing complications such as strictures, abscesses and fistulas that require surgical management. After resection of a diseased intestinal segment, CD recurrence concerns up to 60% of patients within a year post surgery. The mucosa just above the site of the intestinal anastomosis is at particularly high risk of relapse. Prophylactic medical therapy to prevent recurrence has been shown to be effective with a variety of medications, but the recurrence rate remains high, demanding that a better risk stratification of patients be achieved. Recognized risk factors for postsurgical CD recurrence include young age at diagnosis and at surgery, smoking, need for repeated surgeries and penetrating disease. These patients require full dose immunosuppressive or anti-tumor necrosis factor (anti-TNF) therapy, which should be initiated in the immediate postoperative period, to prevent the onset of an inflammatory activity in the bowel. Systematic follow-up by endoscopy to monitor treatment benefit should also be part of the management, as endoscopic recurrence heralds clinical relapse in these patients. The role of noninvasive markers of mucosal inflammation, such as stool calprotectin levels, show promise to complete this monitoring. Although the efficacy of mesalazine and imidazole antibiotics has been long recognized, more aggressive approaches, such as thiopurines and anti-TNF antibodies, have shown higher efficacies in direct comparison trials. The potential place of anti-homing agents is not yet defined, but these agents should in principle be of interest for this prophylactic indication due to their mode of action and interesting side-effect profile. The current recommendations are based on a step-up approach that includes immunosuppressors and/or imidazole antibiotics, followed by an anti-TNF agent, such as infliximab and adalimumab, both already tested in randomized trials in this indication. When endoscopic recurrence is identified during follow-up, upscaling to anti-TNF or dose escalation is advocated.

Background: Appropriateness criteria for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC) have been developed by expert panels. Little is known about the acceptance of such recommendations by care providers. The aim was to explore how treatment decisions of practicing gastroenterologists differ from those of experts, using a vignette case study and a focus group. Methods: Seventeen clinical vignettes were drawn from clinical indications evaluated by the expert panel. A vignette case questionnaire asking for treatment options in 9 or 10 clinical situations was submitted to 26 practicing gastroenterologists. For each vignette case, practitioners’ answers on treatments deemed appropriate were compared with panel decisions. Qualitative analysis was performed on focus group discussion to explore acceptance and divergence reasons. Results: Two hundred thirty-nine clinical vignettes were completed, 98 for CD and 141 for UC. Divergence between proposed treatments and panel recommendations was more frequent for CD (34%) than for UC (27%). Among UC clinical vignettes, the main divergences with the panel were linked to 5-aminosalicylate (5-ASA) failure assessment and to situations in which stopping treatment was the main decision. For CD, the propositions of care providers diverged from the panel in mild to moderate active disease, for which practitioners were more prone to an accelerated step-up than the panel’s recommendations. Conclusions: In about one-third of vignette cases, inflammatory bowel disease treatment propositions made by practicing gastroenterologists diverged from expert recommendations. Practicing gastroenterologists may experience difficulty in applying recommendations in daily practice.

Background and Aims: The prospective, observational Swiss Eosinophilic Esophagitis Cohort Study (SEECS) was set up in 2015 with the following goals in mind: (1) to provide up-to-date epidemiologic data; (2) to assess the appropriateness of care; (3) to evaluate the psychosocial impact; and (4) to foster translational research projects. Data capture relies on validated instruments to assess disease activity and focuses on epidemiologic variables and biosamples (esophageal biopsies and blood specimens). An annual inclusion of 70 new patients with eosinophilic esophagitis (EoE) or proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is intended. We herein describe the SEECS cohort profile. Methods: The SEECS includes adult patients (age ≥18 years) with EoE or PPI-REE diagnosed according to published criteria. After inclusion, the patients are typically seen once a year for a clinical and endoscopic/histologic follow-up examination. Data are captured using validated questionnaires. Biosamples from patients with gastroesophageal reflux disease (GERD) and controls with a healthy esophagus are collected as well. Results: From January 2016 to July 2017, a total of 111 patients with EoE and 10 patients with PPI-REE were recruited. In addition, esophageal biopsies and blood samples from 11 patients with GERD and 20 controls with a healthy esophagus were collected. The mean age of the patients with EoE and those with PPI-REE was 39.6 ± 12.9 and 44.6 ± 15.6 years, respectively. A male predominance was found among both the patients with EoE (77.5%) and those with PPI-REE (70%). Concomitant allergic disorders were found in 79.3% of the patients with EoE and 90% of the patients with PPI-REE. At inclusion, the EoE patients were treated with the following therapeutic regimens: no therapy (0.9%), PPI (36%), swallowed topical corticosteroids (82.9%), elimination diets (15.3%), and esophageal dilation (19.8%). Conclusions: The SEECS is the first national cohort study of patients with EoE or PPI-REE. The SEECS will provide up-to-date epidemiologic data and foster translational research projects.

Ulcerative colitis (UC) has a prevalence of 1 in 1000 inhabitants in Switzerland. The diagnosis of UC is based on a typical clinical presentation that involves bloody diarrhea, characteristic endoscopic features with continuous inflammation involving the rectum, and compatible histology. UC develops in genetically susceptible individuals with a dysregulated mucosal immune system. This article highlights latest insights into the pathogenesis, diagnosis, and therapy of UC.La rectocolite ulcéro-hémorragique (RCUH) représente une maladie fréquente en Suisse avec une prévalence de 1 sur 1000 habitants. Le diagnostic se base sur la présentation clinique typique avec des diarrhées sanglantes, une image endoscopique caractéristique avec une inflammation continue qui touche pratiquement toujours le rectum, et une image histologique compatible. La RCUH se développe chez des individus avec prédisposition génétique et une dérégulation du système immunitaire colique. Cet article fait le point sur la pathogenèse, le diagnostic et les approches thérapeutiques de cette maladie.

Background/Aims: Evidence for the effectiveness of methotrexate (MTX) in treating inflammatory bowel disease (IBD) is still incomplete. This study assessed the effectiveness, safety and mucosal healing in IBD patients treated with MTX in the Swiss IBD Cohort. Methods: Efficacy was defined by physician assessment or by CD activity index Results: MTX was administered to 341 patients (262 CD; 79 UC) out of 2,660 patients. MTX effectiveness was 59.5% (128/215) in CD and 40.0% (24/60) in UC (chi2 = 7.2409, p = 0.007). Among patients on MTX therapy at the time of analysis, remission was obtained in 87.4% (76/87) and 69.2% (9/13) for CD and UC patients respectively. The median duration of MTX therapy was 40 months for CD and 15 months for UC. Occurrence of adverse events was the first reason for treatment discontinuation (39.4% of all cases). The rate of mucosal healing with MTX was 9.5% for CD and 25% for UC patients respectively. Conclusion: MTX therapy was effective for the induction and maintenance therapy in IBD patients, with only a modest mucosal healing ability.

BACKGROUND Extraintestinal manifestations (EIMs) in patients with inflammatory bowel disease (IBD) are frequently observed. Little is known about the efficacy of anti-tumor necrosis factor (TNF) in EIM management. We assessed the effect of 3 anti-TNF agents (infliximab, adalimumab, and certolizumab pegol) on EIM evolution. METHODS Data on 1249 patients from the Swiss IBD Cohort Study (SIBDCS) were analyzed. All EIMs were diagnosed by relevant specialists. Response was classified into improvement, stable disease, and clinical worsening based on the physician's interpretation. RESULTS Of the 366 patients with at least 1 EIM, 213 (58.2%) were ever treated with an anti-TNF. A total of 299 treatments were started for 355 EIMs. Patients with EIM were significantly more often treated with anti-TNF compared with those without EIM (58.2% versus 21.0%, P < 0.001). Infliximab was the most frequently used drug (63.2%). In more than 71.8%, a clinical response of the underlying EIM to anti-TNF therapy was observed. In 92 patients (43.2%), anti-TNF treatments were started for the purpose of treating EIM rather than IBD. Response rates to anti-TNF were generally good and best for psoriasis, aphthous stomatitis, uveitis, and peripheral arthritis. In 11 patients, 14 EIM occurred under anti-TNF treatment. CONCLUSIONS Anti-TNF was frequently used among patients with EIM. In more than 40%, anti-TNF treatments are started to treat EIM rather than IBD. Given the good response rates, anti-TNF seems to be a valuable option in the treatment of EIM, whereas appearance of EIM under anti-TNF does not seem to be a source of considerable concern.

Background Patient-reported disease perceptions are important components to be considered within a holistic model of quality of care. Gender may have an influence on these perceptions. We aimed to explore gender-specific concerns of patients included in a national bilingual inflammatory bowel disease cohort. Methods Following a qualitative study, we built a questionnaire comprising 37 items of concern. Answers were collected on a visual analog scale ranging from 0 to 100. Principal axis factor analysis was used to explore concern domains. Linear multiple regressions were conducted to assess associations with patient characteristics. Results Of 1102 patients who replied to the survey, 54% were female and 54% had Crohn’s disease. We identified six domains of concern: socialization and stigmatization, disease-related constraints and uncertainty, symptoms and their impact on body and mind, loss of body control (including sexuality), disease transmission, and long-term impact of the disease. Cancer concerns were among the highest scored by all patients (median 61.8). Severity of symptoms was the only factor associated with concerns, unrelated to dimension and gender (p40 years decreased disease-related constraints and uncertainty concerns, and being at home or unemployed increased them. Treatments were associated with increased socialization and stigmatization and with increased disease-related constraints and uncertainty concerns in men. Overall, psychosomatic characteristics were highly associated with concerns for both men and women. Depending on the concern dimensions, increased levels of concern were associated with the highest signs of anxiety in women or depression in men, as well as lower health-related quality of life in men. Conclusions Patients have numerous concerns related to their illness that need to be reassessed regularly. Concerns differ between men and women, suggesting that information and communication about the disease should take gender differences and subjective perceptions of quality of life into consideration.

BACKGROUND The onset of inflammatory bowel disease (IBD) during childhood/adolescence compromises peak bone mass acquisition and predisposes to fractures later in life. However, the structural basis for bone fragility in young adults with IBD remains unknown. METHODS One hundred two young subjects from the Swiss IBD cohort were included. Areal bone mineral density (aBMD) at distal radius, hip, and spine as well as morphometric vertebral fractures were assessed using dual-energy x-ray absorptiometry technique. Volumetric (v)BMD, trabecular, and cortical bone microstructure at the distal radius and tibia were assessed by high-resolution peripheral quantitative computed tomography. Areal, vBMD, and microstructure were compared between patients with IBD and healthy matched controls (n = 389). Multiple regression analysis was used to evaluate variables associated with bone microarchitecture and fractures. RESULTS Clinical fractures were reported in 37 IBD subjects (mean age 23 yrs), mostly of the forearm; 5 subjects had morphometric vertebral fractures. After adjusting for age, sex, and height, tibia trabecular (Tb)vBMD, thickness, and distribution were significantly associated with fractures, whereas aBMD was not. After adjusting for aBMD, radius Tb distribution and tibia (Tb)vBMD and trabecular thickness still remained associated with fractures. Compared with healthy controls, patients with IBD had significantly lower aBMD at all sites, as well as alteration in (Tb)vBMD and trabecular microstructure at the distal radius and tibia, and these alterations were correlated with disease severity. CONCLUSIONS Young patients with IBD have low aBMD and altered trabecular bone microarchitecture compared with healthy controls. The latter is independently associated with fractures and may predispose increased susceptibility to fragility fractures throughout life.

Background Anti-TNFα agents are commonly used for ulcerative colitis (UC) therapy in the event of non-response to conventional strategies or as colon-salvaging therapy. The objectives were to assess the appropriateness of biological therapies for UC patients and to study treatment discontinuation over time, according to appropriateness of treatment, as a measure of outcome. Methods We selected adult ulcerative colitis patients from the Swiss IBD cohort who had been treated with anti-TNFα agents. Appropriateness of the first-line anti-TNFα treatment was assessed using detailed criteria developed during the European Panel on the Appropriateness of Therapy for UC. Treatment discontinuation as an outcome was assessed for categories of appropriateness. Results Appropriateness of the first-line biological treatment was determined in 186 UC patients. For 64% of them, this treatment was considered appropriate. During follow-up, 37% of all patients discontinued biological treatment, 17% specifically because of failure. Time-to-failure of treatment was significantly different among patients on an appropriate biological treatment compared to those for whom the treatment was considered not appropriate (p = 0.0007). Discontinuation rate after 2 years was 26% compared to 54% between those two groups. Patients on inappropriate biological treatment were more likely to have severe disease, concomitant steroids and/or immunomodulators. They were also consistently more likely to suffer a failure of efficacy and to stop therapy during follow-up. Conclusion Appropriateness of first-line anti-TNFα therapy results in a greater likelihood of continuing with the therapy. In situations where biological treatment is uncertain or inappropriate, physicians should consider other options instead of prescribing anti-TNFα agents.

Objective: Macrophages play a critical role in intestinal wound repair. However, the molecular pathways that regulate macrophage wound repair activities remain poorly understood. The aim of this study was to evaluate the role of GM-CSF receptor signaling in the wound repair activities of macrophages. Methods: Murine macrophages were differentiated from bone marrow cells and human macrophages from monocytes isolated from peripheral blood mononuclear cells of Crohn's disease (CD) patients. In vitro models were used to study the repair activities of macrophages. Results: We provide evidence that GM-CSF receptor signaling is required for murine macrophages to promote epithelial repair. In addition, we demonstrate that the deficient repair properties of macrophages from CD patients with active disease can be recovered via GM-CSF therapy. Conclusion: Our data support a critical role of the GM-CSF signaling pathway in the pro-repair activities of mouse and human macrophages.

Background: The knowledge about risk factors for the onset of uveitis manifestations in patients with inflammatory bowel disease (IBD) is still limited. Here, we aimed to provide an overview of the clinical factors associated with the onset of uveitis in the Swiss IBD Cohort Study (SIBDCS). Methods: We included epidemiological and clinical data from 1840 patients with Crohn’s disease (CD) and 1426 patients with ulcerative colitis (UC) followed up in the SIBDCS between 2006 and 2018. Associations between disease characteristics and uveitis were assessed in univariate and multivariate analyses. Results: Overall, we identified 285 patients with uveitis. Uveitis was more frequent in patients with CD (11.1%; 205 of 1635) than UC (5.6%; 80 of 1346; odds ratio 2.11, p Conclusions: Our data demonstrate that uveitis in IBD occurs more often in CD as well as in women and is associated with a more severe disease course. This might guide physicians’ awareness in at-risk patients to the presence of uveitis extraintestinal manifestations and help to improve patient care.

Background Safety and economic issues have increasingly raised concerns about the long term use of immunomodulators or biologics as maintenance therapies for Crohn's disease (CD). Despite emerging evidence suggesting that stopping therapy might be an option for low risk patients, criteria identifying target groups for this strategy are missing, and there is a lack of recommendations regarding this question. Methods Multidisciplinary European expert panel (EPACT-II Update) rated the appropriateness of stopping therapy in CD patients in remission. We used the RAND/UCLA Appropriateness Method, and included the following variables: presence of clinical and/or endoscopic remission, CRP level, fecal calprotectin level, prior surgery for CD, and duration of remission (1, 2 or 4 years). Results Before considering withdrawing therapy, the prerequisites of a C-reactive protein (CRP) and fecal calprotectin measurement were rated as “appropriate” by the panellists, whereas a radiological evaluation was considered as being of “uncertain” appropriateness. Ileo-colonoscopy was considered appropriate 1 year after surgery or after 4 years in the absence of prior surgery. Stopping azathioprine, 6-mercaptopurine or methotrexate mono-therapy was judged appropriate after 4 years of clinical remission. Withdrawing anti-TNF mono-therapy was judged appropriate after 2 years in case of clinical and endoscopic remission, and after 4 years of clinical remission. In case of combined therapy, anti-TNF withdrawal, while continuing the immunomodulator, was considered appropriate after two years of clinical remission. Conclusion A multidisciplinary European expert panel proposed for the first time treatment stopping rules for patients in clinical and/or endoscopic remission, with normal CRP and fecal calprotectin levels.

BackgroundIron deficiency is a common and undertreated problem in inflammatory bowel disease (IBD).AimTo develop an online tool to support treatment choice at the patient-specific level.MethodsUsing the RAND/UCLA Appropriateness Method (RUAM), a European expert panel assessed the appropriateness of treatment regimens for a variety of clinical scenarios in patients with non-anaemic iron deficiency (NAID) and iron deficiency anaemia (IDA). Treatment options included adjustment of IBD medication only, oral iron supplementation, high-/low-dose intravenous (IV) regimens, IV iron plus erythropoietin-stimulating agent (ESA), and blood transfusion. The panel process consisted of two individual rating rounds (1148 treatment indications; 9-point scale) and three plenary discussion meetings.ResultsThe panel reached agreement on 71% of treatment indications. ‘No treatment’ was never considered appropriate, and repeat treatment after previous failure was generally discouraged. For 98% of scenarios, at least one treatment was appropriate. Adjustment of IBD medication was deemed appropriate in all patients with active disease. Use of oral iron was mainly considered an option in NAID and mildly anaemic patients without disease activity. IV regimens were often judged appropriate, with high-dose IV iron being the preferred option in 77% of IDA scenarios. Blood transfusion and IV+ESA were indicated in exceptional cases only.ConclusionsThe RUAM revealed high agreement amongst experts on the management of iron deficiency in patients with IBD. High-dose IV iron was more often considered appropriate than other options. To facilitate dissemination of the recommendations, panel outcomes were embedded in an online tool, accessible via http://ferroscope.com/.

Crohn's disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural damage to the bowel, which may predict long-term disability, is needed. The aim of this article is to outline the methods to develop an instrument that can measure cumulative bowel damage. The project is being conducted by the International Program to develop New Indexes in Crohn's disease (IPNIC) group. This instrument, called the Crohn's Disease Digestive Damage Score (the Lemann score), should take into account damage location, severity, extent, progression, and reversibility, as measured by diagnostic imaging modalities and the history of surgical resection. It should not be "diagnostic modality driven": for each lesion and location, a modality appropriate for the anatomic site (for example: computed tomography or magnetic resonance imaging enterography, and colonoscopy) will be used. A total of 24 centers from 15 countries will be involved in a cross-sectional study, which will include up to 240 patients with stratification according to disease location and duration. At least 120 additional patients will be included in the study to validate the score. The Lemann score is expected to be able to portray a patient's disease course on a double-axis graph, with time as the x-axis, bowel damage severity as the y-axis, and the slope of the line connecting data points as a measure of disease progression. This instrument could be used to assess the effect of various medical therapies on the progression of bowel damage. RI Loftus, Edward/E-8304-2011; Schreiber, Stefan/B-6748-2008

Background: In 2013, a ECCO survey showed that a minority of IBD specialists was aware and confident about the benefits and issues of biosimilars. We aimed to look at the evolution of IBD specialists' thinking about biosimilars one year after they had become available in the European Union. Methods: A 14-question anonymous survey was posted on the ECCO website. Members voluntarily responded in response to ECCO office invitations to participate in their surveys. Information on gender, job position, country, and experience with biologics also were collected. Results: Out of the 118 responders, only 17% of responders had no access to biosimilars. Most responders regarded cost-sparing [92.4%] as the main advantage of biosimilars, considered immunogenicity [69%] to be their main concern, and estimated that post-marketing pharmacovigilance, well-designed randomized clinical trials and further studies of risk profile were needed [30.5%, 27%, 32.2%, respectively, a 30-40% reduction since 2013]. Only 35% of physicians think biosimilars should carry distinct International Nonproprietary Names, as compared with 66% in 2013, and 89.8% disagreed with automatic substitution of the originator with a biosimilar by a pharmacist. The originator and biosimilar were considered interchangeable by 44.4% of responders, as compared with 6% in 2013. Only 32.2% were against the extrapolation across indications, and only 25% would not extrapolate data across IBD. Finally, only 19.5% felt little or no confidence in the use of biosimilars, as compared with 63% in 2013. Conclusion: IBD specialists are generally well informed and educated about biosimilars. Compared with in 2013, there are now fewer concerns and more confidence about their use in clinical practice.

Background Perceptions of appropriateness of treatments may differ between gastroenterologists (GIs) and inflammatory bowel disease (IBD) patients. The aim of this study was to explore and compare GIs' and patients' perceptions of risks and benefits of treatments and prioritization of expected outcomes. Methods Four vignette cases were drawn from clinical situations and used in three independent focus groups with GIs (n = 7), ulcerative colitis (UC-p, n = 8) and Crohn's disease patients (CD-p, n = 6). Content analysis was performed based on the conversation transcripts. Results UC-p agreed more often with GIs' treatment choices than CD-p. CD-p often considered 5-ASA as a placebo. UC-p saw topical 5-ASA as a temporary solution, neither comfortable nor practical when professionally active. Azathioprine was considered as the treatment for which the risks versus benefits were perceived as the highest. The main risk perceived by patients on anti-TNFs was a potential loss of response. Divergences were observed on 1) stop of treatment: UC-p did not easily concur with stopping a treatment, which differed from GIs' expectation of patients' perceptions; CD-p were more prone to consider stopping treatment than GIs, 2) perception of outcomes: physicians had a focus on long-term objective goals. Patients' expectations were of shorter term and mainly concerned stress management, nutritional advice, and information on the treatments effects. Conclusions Overall, patients and GIs agreed on perceptions of IBD treatments. GIs seemed more concerned about objective and scientific measures of remission whereas patients focused on quality of life and social outcomes when it came to evaluating a therapy.

BACKGROUND: Inflammatory Bowel Disease (IBD) patients are confronted with needs and concerns related to their disease. AIM: To explore information expectations of patients included in a national bilingual IBD cohort in Switzerland (SIBDC). METHODS: This is a mixed-methods study, comprising 1) a semi-narrative survey sent to 1506 patients from the SIBDC and 2) two focus groups conducted with 14 patients to explore and assess the relevance of the survey's findings. Data collected within the framework of the SIBDC was used to characterize survey's responders. RESULTS: 728 patients (48%) replied to the survey: 52.5% females, 56% Crohn's disease (CD), 87% secondary/tertiary level educated, 70% full/part-time employed. On average, 47% of patients sought for information, regardless of the disease stage; 27% of them were dissatisfied with information received at the time of first symptoms. During flares, 43% were concerned about drugs and therapies; in remission, 57% had concerns on research and developments; 27% searched for information linked to daily disease management. Information-seeking increased when active disease, for CD with high levels of perceived stress (OR = 2.47; p = 0.003), and for all with higher posttraumatic stress symptoms. The focus groups confirmed a perceived lack of information about general functioning, disease course, treatments and their risks, extra-intestinal symptoms and manifestations. CONCLUSIONS: Information remains insufficient for IBD patients. Lack of information in specific domains can potentially cause stress and hinder detection of symptoms. Better information should be considered as a potentially important component in improving patients' outcomes in IBD.