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: Inflammatory bowel disease (IBD) needs early interventions and an individual specialist–patient relationship. Distance from a tertiary IBD center might affect patient’s disease course and outcome. We investigated whether the patient-to-specialist distance has an impact on the disease course using the well-defined patient collective of the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). Methods: Patient’s home address at diagnosis (postal zip code) was extracted from the SIBDCS database. Distance between each zip code and the nearest located IBD specialist center was calculated and classified into the following three sections based on proximity: <10 km (group 1); 10–35 km (group 2); >35 km (group 3). Results: Our study included in total 408 IBD patients [234 Crohn’s disease (CD), 154 ulcerative colitis (UC), 20 IBD unclassified (IBDU)]. Median age was lowest in group 2 at diagnosis (G1: 28 years; G2: 21 years, G3: 26 years, p < 0.01). The diagnostic delay did not differ between groups. CD patients in group 1 were treated more often with anti-tumor necrosis factor (TNF) agents (72% versus 56%, p = 0.04) and 5-aminosalicylates (44% versus 28%, p = 0.04) than in group 3. UC/IBDU patients in group 1 were treated more often with corticosteroids than patients in group 3 (83% versus 58%, p < 0.01). The occurrence of IBD-related surgeries did not differ between groups. Conclusions: Patient-to-specialist distance might affect drug treatment. However, disease course and the need for IBD-related surgery does not seem to be associated with a longer distance to specialist care in Switzerland.

Inflammatory bowel disease (IBD) affects patients during their peak reproductive years. This raises important questions, in both patients and healthcare providers, regarding conception, pregnancy, and breastfeeding. Lack of information and insufficient communication among healthcare providers can leave patients with limited information and even contradictory advice. Given the fact that pregnant and/or breastfeeding IBD patients are excluded from clinical studies the evidence on many questions related to pregnancy and postpartum period is limited. However, there exists increasing data from case series and cohort studies that allows to provide clinical guidance. The overarching concept is that optimizing the mother’s health is critical for optimizing the health of the unborn child and benefit of continuing medical therapy in IBD during pregnancy outweighs possible risks in most instances. This paper provides an up-to-date systematic review of the literature on IBD in pregnancy and proposes guidance to questions frequently encountered by healthcare professionals.

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: 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.

Biologics are effective and have a good safety profile in the treatment of inflammatory bowel disease. Biosimilars have recently become available as treatment option. They are biological agents that are highly similar to the original biologic compound in their structure, biological activity, efficacy and safety. This position paper summarises current knowledge on biosimilars and presents its statements on regulatory issues and clinical situation in order to provide clinicians adequate information for them to reach informed and appropriate shared decision-making with their patients.

Background/Aims Extraintestinal manifestations (EIM) involving joints, skin, eyes and liver represent an important problem in the treatment of IBD patients. The aim of this study was to identify factors that are associated with the occurrence of joint EIM and therefore allow an early diagnosis and guide medical treatment. Methods We studied clinical and epidemiological data from 3298 patients included in the Swiss IBD Cohort Study (SIBDCS), 1860 suffered from Crohn’s disease (CD) and 1438 from ulcerative colitis or IBD unclassified (UC/IBDU). Results We found female gender as well as a longer disease duration and activity (specified as CDAI or MTWAI, respectively) to be related to the appearance of arthritis/arthralgia, but also sacroiliitis/ankylosing spondylitis in IBD patients. IBD patients with arthritis/arthralgia or sacroiliitis/ankylosing spondylitis were more often treated with anti-TNF and patients with arthritis/arthralgia underwent more often IBD-related surgeries. We revealed that eye or skin EIM were more frequent in patients with arthritis/arthralgia or sacroiliitis/ankylosing spondylitis. In multivariate analysis, we confirmed female gender, longer disease duration, IBD-related surgery, presence of other EIM and treatment with anti-TNF to be independent risk factors for the onset of arthritis/arthralgia in CD and UC/IBDU patients. Conclusion In this study, we demonstrated that markers for a more severe disease course were associated with the onset of joint EIM in IBD patients. Our data suggest that in particular females under anti-TNF treatment and patients suffering from non-joint and/or IBD-related surgery should be close and carefully monitored for presence of arthritis or sacroiliitis/ankylosing spondylitis.

Background Many inflammatory bowel disease (IBD) patients follow a restrictive diet due to perceived positive effects on their symptoms. We assessed the prevalence of vegetarian (VD) and gluten-free diets (GFDs) in IBD patients, the reasons for following such a diet, and whether nutrition has an impact on disease activity and microbiota composition. Methods We included 1254 patients from the Swiss Inflammatory Bowel Disease Cohort Study with prospective acquisition of clinical data and psychosocial, disease-related and lifestyle factors between 2006 and 2015. Dietary habits were assessed through a self-report questionnaire. In 92 patients, we analysed intestinal mucosa-associated microbial composition using high-throughput sequencing. Results Overall, 4.1% (n = 52) of the patients reported following a VD and 4.7% (n = 54) a GFD. No differences regarding disease activity, fistula, hospitalization or surgery rates were observed. Patients on a VD or GFD had significantly higher levels of post-traumatic stress symptoms. Furthermore, GFD patients had significantly higher anxiety and depression symptom levels. The gut microbiota composition in IBD patients following a VD or GFD was significantly different compared to that of omnivores. Conclusions Although we did not identify a relevant impact of a specific diet on the course of the disease, there was a significant association with lower psychological well-being in VD and GFD patients.

Proton pump inhibitors (PPI) have long been considered as devoid of any toxicity, but recent studies have uncovered significant potential side effects related to long-term use. In addition, stopping treatment with PPI may cause a symptomatic rebound effect of acid production. This article reviews the current literature on strategies for rationalizing their use, limiting potential adverse effects and progressive discontinuation.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are predisposed to pneumococcal infections due to their underlying disease and iatrogenic immunosuppression. Vaccination with the 13-valent pneumococcal conjugated vaccine (PCV13) is recommended, but with poor take-up and few data available. We performed an open-label, phase IV, multicenter study to evaluate the safety and immunogenicity of PCV13 in adults with IBD and to analyze the influence of immunomodulating treatments on anti-pneumococcal seroresponses. METHODS: We enrolled 306 patients with IBD from March 2014 through February 2016, with the following exclusion criteria: current IBD flare, pregnancy, pneumococcal immunization in the previous 5 years, and influenza immunization in the previous 4 weeks. PCV13 was administered intramuscularly. Serotype-specific vaccine responses were evaluated using an opsonophagocytic assay. Adverse events were monitored by diary cards and standardized phone interviews. RESULTS: The median seroprotection rate increased significantly from 43.9% (95% confidence interval [CI], 42.3-45.5) at inclusion to 90.4% (95% CI, 89.5-91.3%; P < 0.001) after vaccination. Patients receiving anti-tumor necrosis factor agents achieved a slightly lower seroprotection rate (from 44.5% [95% CI, 42.3%-46.8%] to 86.6% [95% CI, 84.9%-88.1%]) than patients treated with other types of immunosuppressive regimens (thiopurine, methotrexate, oral corticosteroids; from 44.7% [95% CI, 41.7%-47.7%] to 93.8% [95% CI, 92.1%-95.2%]) or nonimmunosuppressive treatment (5-aminosalicylate, topical corticosteroids, vedolizumab; from 41.3% [95% CI, 37.9%-44.8%] to 95.2% [95% CI, 93.4%-96.6%]). There were no safety issues. DISCUSSION: Overall, the administration of PCV13 was highly immunogenic and well tolerated, irrespective of the baseline treatment, and should be encouraged in all adults with IBD.

BACKGROUND:Extraintestinal manifestations (EIM) contribute significantly to the burden of disease in inflammatory bowel disease (IBD). Pain is a leading symptom in IBD and could be seen as an EIM itself. Treatment of IBD associated pain is challenging and insufficiently studied. A better knowledge on the association of pain and IBD specific treatment is warranted to improve the management of IBD patients.METHODS:All patients of the Swiss IBD Cohort Study (SIBDCS) (n = 2152) received a questionnaire regarding pain localization, pain character, and the use of IBD specific medication.RESULTS:1263 completed questionnaires were received. Twenty-one out of 184 patients (10%) receiving anti-TNF treatment compared to 142 out of 678 patients (21%) not receiving anti-TNF medication reported elbow pain (p = 0.002) while 28 out of 198 patients (14%) receiving steroid treatment significantly more often reported elbow pain compared to 59 from 696 patients (8%) not receiving steroids (p = 0.021). Furthermore, we found significantly more female patients under anti-TNF treatment to report knee/ lower leg pain and ankle/ foot pain compared to their male counterparts (36% vs. 20% and 22% vs. 10%, respectively, p = 0.015 for both comparisons). The frequency of knee, lower leg, ankle and foot pain was especially low in male patients under anti-TNF treatment, indicating a high benefit of male patients from anti-TNF therapy regarding EIM.CONCLUSIONS:The frequency of elbow pain was lower in IBD patients treated with anti-TNF but higher in patients treated with steroids.

BackgroundThe frequency of upper gastrointestinal [GI] tract involvement in Crohn`s disease [CD] has been reported with a large variation. Risk factors and disease course of patients with upper GI tract involvement remain largely elusive.MethodsData on CD patients in the Swiss Inflammatory Bowel Disease Cohort were analysed. Patients with upper GI tract involvement were compared with controls. Logistic regression models for prediction of upper GI tract involvement and Cox proportional hazard models for occurrence of complications were computed.ResultsWe included 1638 CD patients, of whom 107 [6.5%] presented with upper GI tract involvement at the time of diagnosis and 214 [13.1%] at any time. Prevalence of such involvement at diagnosis increased over time [5.1% for 1955-95 versus 11.3% for 2009-16]. In a multivariate logistic regression model, male sex and diagnosis between 2009 and 2016 [versus before 1995] were independent predictors for presence of upper GI tract involvement at CD diagnosis (odds ratio [OR] 1.600, p = 0.021 and OR 2.686, p < 0.001, respectively), whereas adult age was a negative predictor [OR 0.388, p = 0.001]. Patients with upper GI tract involvement showed a disease course similar to control patients (hazard ratio [HR] for any complications 0.887, (95% confidence interval [CI] 0.409-1.920), and a trend towards occurrence of fewer intestinal fistulas [log-rank test p = 0.054].ConclusionsPrevalence of upper GI tract involvement has been increasing over the past decades. Male sex and young age at diagnosis were identified as the main predictive factors for such involvement at CD diagnosis. Involvement of upper GI tract did not result in a worse outcome.

at two institutions.The efficacy of infliximab maintenance treatment was evaluated by the rate of sustained clinical benefit, which was estimated using the Kaplan-Meier method.Sustained clinical benefit was defined as the lack of treatment failure.Treatment failure was defined as the discontinuation of infliximab, dose escalation, or surgery for Crohn's disease.Combination therapy with infliximab and IM was defined as the initiation of IM within 6 weeks from the first administration of infliximab and continuation until 14 weeks.Combination therapy was divided into IM naïve and IM exposed group.IM naïve and IM exposed group were defined as receiving IM treatment for less and more than 3 months prior to infliximab administration, respectively.Sustained clinical benefits of infliximab according to the type of IM treatment were investigated using the log-rank test.Results: A total of 341 patients were included in this study (median age, 29.7 years), 90 were female.Of these, 243 patients received combination therapy.Of the 243 patients, 211 and 32 patients were administered azathioprine (AZA) and 6-mercaptopurine (6-MP), respectively.Of these, 83 and 126 patients were treated with 25 and 50 mg of AZA once a day, respectively.In addition, 23 patients were treated with 30 mg of 6-MP once a day.There were 190 patients in the IM naïve group and 53 patients in the IM exposed group.The 5 and 10year cumulative sustained clinical benefit rates in all patients were 49% and 39%, respectively.Sustained clinical benefit rates were significantly higher in patients receiving a combination of infliximab and AZA than in those receiving infliximab monotherapy.Whereas, there was no significant difference in sustained clinical benefit rates between patients receiving a combination of infliximab and 6-MP and infliximab monotherapy.Patients receiving a combination of infliximab and AZA in IM naïve, but not IM exposed group achieved a significantly higher clinical benefit than those receiving infliximab monotherapy.Sustained clinical benefit in patients receiving a combination of infliximab and either 25 or 50 mg of AZA was significantly higher than that in patients treated with infliximab monotherapy (Figure 1).Conclusions: Our data suggested that the combination of infliximab and low dose AZA (25 or 50 mg) as early as possible resulted in the better clinical outcome in Japanese patients with Crohn's disease.

Background: A medical intervention with sequential rescue treatments among patients with steroid refractory ulcerative colitis showed encouraging results, with lower adverse events (AE) risk than previously reported. Despite the potential risk, many patients like to have additional rescue therapies to avoid colectomy. Our recent study showed that a second or even third line rescue therapy in steroid-refractory UC patients might reduce the colectomy rate at one year. Still, it is unknown whether sequential therapies will only postpone colectomy and what percentage of patients will remain in a long- term remission. Aim: To evaluate two-year outcome of the cohort of patients with refractory UC treated either with single or sequential rescue therapies. Methods: The outcome after two years follow up of the cohort of 108 patients with steroid-refractory moderate to severe ulcerative colitis treated with a single or sequential rescue treatments with Infliximab (5mg/kg intravenously at week 0, 2, 6 and then every 8 weeks), Cyclosporine (iv CsA 2mg/kg/daily and then oral CsA 5mg/kg/daily) or Tacrolimus (0.05mg/kg divided in 2 doses, aiming for serum trough levels of 7–12 ng/mL) was retrospectively evaluated. The primary endpoint was two-year colectomy rate; the secondary endpoint was corticosteroid free remission rate. Results: Out of 108 patients in the primary cohort, 103 patients (95%) were followed at least 2 years; 74/76 patients treated with single, 23/26 patients with double and all 6 patients on triple rescue treatment. Five patients were lost to follow up (FUP). Two-year colectomy rate was non-significantly increased to 25% (26/103) compared to 18% (19/108) after first year (p=0.121, OR 1.69; 95% CI 0.87–3.30). During the 2nd year of FUP no new colectomy was observed among the group of patients with triple rescue treatments (3/6 after 1st year), while among the patients on the double rescue treatments only 1 new colectomy was identified. Steroid free remission rate slightly decreased from 39% (42/108) after first year to 30% (31/103) [p=0.118 OR 1.59 CI 0.89–2.86]. The AE rate in the 2nd year of follow up was 13.6% (14/103). Additionally, 14.5% (15/103) of patients were withdrawn from the last rescue agent during 2nd year of FUP. Conclusions: Considering our results, it seems that second and third line rescue therapies in steroid refractory UC have prolonged beneficial effects in avoiding colectomy even two years after the induction. Still, further follow up and adverse effects analysis will be necessary for the estimation of future role of sequential rescue therapies in UC patients.

En 1996, la Société Suisse de Gastroentérologie édite pour la première fois des recommandations consensuelles suisses de suivi postpolypectomie colique et de suivi des cancers colorectaux après opération curative. Ces recommandations ont trouvé une large approbation. En 2014, la Société Suisse de Gastroentérologie a entrepris la quatrième révision.

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.

1996 schuf die damalige Fachgesellschaft der Schweizerischen Gastroenterologen erstmals Empfehlungen zur Nachsorge nach koloskopischer Polypektomie und nach kurativer Operation des kolorektalen Karzinoms. Diese Empfehlungen haben eine breite Akzeptanz gefunden. 2014 ist nun die vierte Revision erfolgt.