Crohn's disease commonly affects women of childbearing age. Available data on Crohn's disease and pregnancy show that women with Crohn's disease can expect to conceive successfully, carry to term and ...deliver a healthy baby. Control of disease activity before conception and during pregnancy is critical, to optimize both maternal and fetal health. Generally speaking, pharmacological therapy for Crohn's disease during pregnancy is similar to pharmacological therapy for non-pregnant patients. Patients maintained in remission by way of pharmacological therapy should continue it throughout their pregnancy. Most drugs, including sulfasalazine, mesalazine, corticosteroids, and immunosuppressors such as azathioprine and 6-mercaptopurine, are safe, whereas methotrexate is contraindicated.
Abstract
Background
Vedolizumab (VDZ) a humanised monoclonal antibody against α4β7 integrin is used in Crohn’s disease (CD) and ulcerative colitis (UC). It is still unclear whether biologic-naive ...patients will respond better to VDZ than TNF-pre-treated patients in a real life setting. Our study aimed to determine the efficacy of VDZ among TNF-pre-treated compared with TNF-naive patients.
Methods
In total, 265 patients of the Swiss IBD cohort study were analysed, 17 patients were excluded due to incomplete data. Of the remaining 248 patients 130 suffered from CD and 118 patients from UC. Remission was defined as calprotectin < 200 mg/kg in faecal samples and/or mucosal healing determined by endoscopy. Endpoints were determined between month 4 and 8 and between month 12 and 16 after VDZ induction.
Results
In total, 112 patients (45%) (43% CD and 48% UC) achieved remission between month 4 and 8 and 130 patients (52%) at month 12 and 16. In patients with UC, significantly more TNF-naïve patients (60%) achieved remission compared with TNF-pre-treated patients (33%) (p = 0.01, OR 0.24, CI 0.09–0.65). In patients with CD however, we observed no significant difference between TNF-pre-treated and TNF-naive patients. Almost a third of all patients discontinued VDZ treatment (29.8%), the most frequent reason was non-response to VDZ (20%), followed by adverse events (6%) and exacerbation of extraintestinal manifestations (3%).
Conclusions
A significant proportion of patients TNF-naïve and TNF-pre-treated patients achieved remission. Previous anti-TNF failure was associated with a lower efficacy of VDZ in UC patients between month 4 and 8, whereas remission rates in anti-TNF–naïve vs. experienced CD patients were similar.
Abstract
Background
Reproduction is an essential part of life. Our aim was to obtain a global perspective on IBD management by gastroenterologists (GIs) during preconception, pregnancy, lactation and ...neonatal period.
Methods
An anonymous survey (75 questions) was developed to investigate different aspects of clinical practice concerning the management of pregnancy and breastfeeding in patients with IBD. A national representative from each European country, USA, Latin America, Australia and New Zealand was selected to distribute the survey among their GI colleagues who treat patients with IBD (irrespectively of their experience).
Results
A total of 856 GIs from 36 countries participated in the survey. Among the participants, 63% had over a decade of experience as GIs, and 61% identified themselves as IBD specialist (IBDologists). The most relevant survey results and sub-analyses based on expertise are presented in tables 1 and 2. In the management of pregnant patients in remission, treatment discontinuation occurred either consistently or occasionally as follows: 20% thiopurines, 37% vedolizumab, 31% ustekinumab, and 96% small molecules. Notably, 13% did not always discontinue small molecules in patients contemplating pregnancy. Safety was the main reason for discontinuing IBD therapy during pregnancy. Contrary to the recommendations in clinical practice guidelines, many GIs avoid starting oral or rectal budesonide, anti-TNF, vedolizumab or ustekinumab during a disease flare. Further, a third of GIs would start thiopurines for a flare during pregnancy. Moreover, 13% will never perform a colonoscopy in a pregnant patient to guide decision making. Half of GIs implemented a dedicated outpatient follow-up program for pregnant patients in remission, with 87% enrolling all pregnant patients in this program. Concerning breastfeeding, 14% believed that all drugs can be used while breastfeeding. Regarding offspring’s vaccination, about 20% recommend against the administration of non-live vaccines and only 50% recommended avoiding live vaccines during the first 12 months for children exposed to anti-TNF in-utero. Among those GIs who recommended delaying vaccines in such cases, only 41% recommended testing the infant for detectable anti-TNF levels if live vaccines were required. Among the surveyed GIs, only a minority had a referral obstetrician, and only 35% referred patients with active or complicated IBD, while 45% had a referral paediatrician with expertise in IBD.
Conclusion
The management of IBD during pregnancy, lactation, and neonatal period is notably suboptimal, even among GIs specifically dedicated to IBD. It is crucial to address this current need and implement urgent educational measures in this area.
Abstract
Background
Knowledge on the impact of stoma formation surgery on course of disease, psychological well-being, quality of life (QoL) and working capacity in patients with IBD is scarce.
...Methods
To investigate this, we analysed prospectively followed-up patients from the Swiss inflammatory bowel disease cohort study (SIBDCS), comparing ulcerative colitis (UC) and Crohn’s disease (CD) with vs without stoma surgery, for both temporary and permanent stoma formation.
Results
From a total of, 3825 SIBDCS patients, 352 patients were included in our analysis -, 176 with stoma surgery (52.8% and, 47.2% with CD and UC, respectively) - amongst these, 111 with permanent and, 65 with temporary stoma - matched with, 176 patients without stoma. Mean and maximal disease activity was lower in patients with vs. without stoma overall in CD but not in UC (Fig., 1, A/B). However, in UC, disease activity was lower in permanent vs. temporary stoma patients (Fig., 1, C/D).
Figure, 1 A-D: Average disease activity with mean Crohn’s disease activity index (CDAI; A) in CD and Modified Truelove & Witts activity index (MTWAI; B) and UC for patients with vs. without stoma as well as (within the stoma group) permanents vs. closed ostomy (C,D).
Furthermore, active EIM as well as need for steroids, immuno-modulators and biologics were lower in stoma vs. control patients. Amongst stoma patients, quality of life and psychological wellbeing was similar in permanent vs. closed stoma (Inflammatory Bowel Disease Quality of Life questionnaire Total score (IBDQ); Hospital Anxiety and Depression Scale Total Score (HADS); Posttraumatic Diagnostic Scale Total Score (PDS); and effort-reward ratio – all mean values obtained during prospective SIBDCS follow-up). However, we found a significantly lower (i.e. more favourable) PDS avoidance score in permanent vs. closed ostomy (Fig., 2A). Working capacity was lower in permanent vs. closed stoma patients (Fig. 2B).
Figure, 2 A,B: IBDQ, HADS total, PDS total and Effort-Reward ratio (A), Working status, absentism from work and need for disability insurance (B) in permanent vs. closed IBD patients with stoma.
Conclusion
In CD patients with stoma surgery disease activity was significantly reduced after ostomy. Moreover, in UC we observed a benefit of patients with permanent compared to their counter-parts with temporary stoma to control disease activity. We found no differences in psychological functioning and QoL between temporary and closed stoma, with the exception of higher avoidance indicative of posttraumatic stress in the latter. In contrast, working capacity revealed to be higher closed vs. permanent ostomy.
Abstract
Background
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 a retrospective 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, profile of users at risk for addiction and the impact of alcohol and cannabis on the course of 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. A logistic regression analysis confirmed a risk of alcohol consumption in male workers > 50 years, whereas cannabis use was only associated with nicotine consumption. Female gender, retirement and being married were protective factors regarding cannabis consumption.
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.
Abstract
Background
Alterations in gut microbial community of IBD patients still present inconsistency among the published studies and importantly did not completely allow for the unique ...identification of microbial signatures of CD and UC. We aimed molecularly to profile the intestinal microbiota of phenotypically and genotypically well-characterised Swiss IBD cohort (SIBDC) patients as well as newly recruited IBD patients in Bern as a local replica set including non-IBD subjects.
Methods
We deeply characterised the microbiota of UC and CD from 941 biopsy samples of 346 patients from the SIBDCS Cohort and 1254 of biopsy samples of total 397 IBD patients and non-IBD subjects from the Bern cohort, thus building one of the largest cohorts covering sequence data generated. The microbiota composition at the site of biopsy was determined by 16S Amplicon sequencing on the Iontorrent platform. Data were analysed using the QIIME pipeline and correlated with the extensive long-term longitudinal clinical data (patients’ disease trajectory) of the Swiss IBD cohort study.
Results
In PCoA plots, CD and UC disease groups clustered into two distinct groups mostly characterised by altered bacterial composition and lower diversity in CD patients compared with UC patients and non-IBD subjects. Significant differences in taxa representation between the disease groups of each cohort were identified using multivariate association with linear models. This microbial “fingerprint” based on the Swiss IBD cohort and Bern cohort data could then be used in a machine learning algorithm process to correctly predict the CD and UC disease groups with more than 83% success rate. Disease status, disease location/behaviour, and stool consistency were the critically important variables that have effects on shaping the gut microbiota of IBD patients, as assessed in both cohort. Steroids and Anti-TNF agents’ responses, as well of surgery also induced several taxonomic changes, but not the response to thiopurines, methotrexate or 5-ASA.
Conclusions
Our findings revealed that CD and UC are two distinct intestinal disorders at the microbiome level, which could be differentiate based on the microbial profile. A loss of beneficial microorganisms is more associated with CD. However, the observed bacterial dysbiosis in IBD patients is not only associated with disease status itself, it is also directly linked to several clinical parameters associated with the disease trajectory of patients.
Abstract
Background
The mechanism of loss of response of anti-tumour necrosis factor alpha (TNFα) agents in inflammatory bowel disease (IBD) patients is poorly understood and long-term prognostic ...markers of therapeutic efficacy are required for ensuring successful clinical treatment.
Methods
An in vitro blood assay was developed to predict patient response to the anti-TNFα agent infliximab. Crohn’s disease (CD) and ulcerative colitis (UC) patients were then classified according to the shedding of an L-selectin (CD62L) from the surface of granulocytes in whole- blood. CD62L shedding was quantified by flow cytometry before and after infliximab administration. A 5-year (June 2015 to August 2017), prospective clinical study, comprised of blinded infliximab management, hospitalisation, complication and surgery, was aimed at validating the long-term predictive value of this test.
Results
We identified 62 patients eligible for the study over a 2-month cycle of infliximab maintenance therapy at our infusion centre at Bern University Hospital. 33 IBD patients, who consented to the study with at least one valid testing (fresh blood), were included. According to the in vitro test, 22 (17 CD and 5 UC) were predicted as responders (PR) and whereas 11 (8 CD and 3 UC) were predicted as non-responders (NR). Five years after study initiation, 72% of PR were still treated with infliximab (suggesting a stable response to infliximab treatment), whereas only 27% of NR remained on treatment (p < 0.05), respectively. The median time spent under Infliximab therapy after CD62L shedding quantification was 45 (IQR 34.25–48.5) and 12 (IQR 3.5–35) months (p = 0.019), in PR and NR respectively. Seven patients (4 in the PR and 3 in the NR group) were lost to follow-up. Thirty-five medico-surgical events occurred, 70% during the first 3 years. Median time to first event was 3 vs. 30 months (p = 0.023), respectively (Kaplan–Meier survival curve).
KM curves of time to first event in months, stratified by response prediction via the anti TNF Assay. P value calculated using the log-rank test. NR, predicted non-responders; PR, predicted responders.
Our assay was a better independent predictor of staying long-term on infliximab (p = 0.056) than any other clinical or biological patients’ characteristics.
Conclusions
An assay-based in vitro test for functional blockade of TNFα (CD62L shedding) provides an excellent long-term (3–5 years) independent predictor of infliximab response in inflammatory bowel disease patients. Testing patients at the beginning of the infliximab maintenance phase could help therapeutic decision making to avoid complications, hospitalisation and surgeries.
Abstract
Background
Tumour necrosis factor (TNF)-inhibitors have markedly improved treatment of ulcerative colitis (UC), but loss of response in the long-term remains a frequent problem. A novel ...anti-TNF agent, golimumab, has been introduced in Switzerland for UC in 2014.
Methods
We aimed for real-word data from 1536 UC patients from the Swiss IBD cohort study (SIBDC). UC patients treated with golimumab from 2014 to 2018 were compared with the remaining SIBDC patients with UC. We also performed a chart review of a subgroup of patients to assess response to golimumab.
Results
Among 90 patients (5.9% of all SIBDCS patients with UC) treated with golimumab, extensive disease (E3) was more frequent compared with the non-golimumab group (n = 1409); (E3: 61% vs. 54%, E2: 37% vs. 33% and E1: 2% vs. 12%, p = 0.005). They had more active disease (average modified Truelove and Witts activity index MTWAI 8 IQR: 4–10 vs. 4 IQR: 2–8, p < 0.001) and more extraintestinal manifestations (56/90 62% vs. 615/1446 43%, p < 0.001). In the golimumab group, previous treatment with infliximab, adalimumab, certolizumab or vedolizumab was common (26 patients ~29% with 0 biologics, 44 patients ~49% with 1, 17 ~19% with 2, 3 3% with 3 biologics) and the rate of prior anti-TNF failure was higher than in the non-golimumab group (p ≤ 0.001 for each biologic). Chart review for 57 patients showed a drop of MTWAI from 7 (IQR: 4–11) at baseline to 3 (IQR: 2–6.5) at 6 months (p = 0.0006) and to 2 (IQR: 1–5) at 12 months (p < 0.0001) upon golimumab therapy (Figure). Similarly, the partial Mayo score decreased from 3 (IQR: 1.75–5.25) to 0.5 (IQR: 0–4, p = 0.0002) and 1 (IQR: 0–3.5, p = 0.001) at 6 and 12 months, respectively. The partial Mayo score was normal for 17/35 patients (30% of original cohort) at 6 months and for 14/28 patients (25% of original cohort) at 12 months, respectively. Golimumab was continued in 23/57 patients beyond 12 months. The most frequent reason for stopping was golimumab failure (21 patients).
Figure. Time course for decrease in disease activity scores upon golimumab therapy. Statistics: Mann–Whitney U test. MTWAI, Modified Truelove and Witts activity index.
Conclusions
Golimumab has been used in Switzerland mainly for UC patients with severe and extensive disease and failure of prior biologic therapy. A quarter of this difficult to treat (70% with ≥ 1 biological treatment failure) patient population could be successfully treated with normalisation of the partial Mayo score at 12 months.
Abstract
Background
The diversity and compositional stability of the gut microbiota over time has repetitively shown to be reduced in patients with IBD. Furthermore, distinctive alterations in ...microbial composition are not only considered a key pathogenic factor promoting intestinal inflammation, but might also affect the gut–brain axis, thereby ultimately impacting psychological well-being. In IBD patients, depressive symptoms and anxiety are frequent co-morbidities. Therefore, we aimed to elucidate a potential interplay between microbial composition and validated psychological outcome measurements in Swiss IBD patients.
Methods
Study participants were 171 patients with available microbial sampling of the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS) who were in clinical remission (to exclude a potential impact of disease activity). All patients completed the Hospitality Anxiety and Depression Scale (HADS), the Perceived Stress Questionnaire (PSQ), the 36-item Short Form Health Survey (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). Mucosa-associated intestinal microbiota composition from intestinal biopsies were sequenced via 16S rRNA high-throughput sequencing.
Results
Regarding α diversity, we found significantly lower diversity in patients with higher perceived stress and no substantial differences in patients with high vs. low levels of anxiety and depressive symptoms, respectively. Beta diversity was significantly different in IBD patients with vs. without depression or anxiety (Figure 1).
Principal component analysis of microbial β diversity according to severity (1 = moderately increased, 2 = severe vs. normal anxiety and depression) of psychological alteration (no UC patients with severe depression in our sample).
Looking at specific OTUs, we found several alterations across groups (overview in Figure 2),
Significant results of the quantitative abundance of specific microbes in correlation with extent of psychological distress (– indicating a negative correlation; q-values: corrected; p value, according to Benjamini and Hochberg false discovery rate).
Including, for instance, significant increases in represents of Proteobacteria, such as Desulfovibrio (p = 0.001) in UC and decreases in numerous genus of Firmicutes, such Lachnospiraceae (p < 0.001) in CD and UC patients with depression or decreases in Lactobacillales (Streptopcoccaceae) in CD patients with anxiety (p < 0.001).
Conclusions
We found significant alterations in the intestinal mucosa-associated microbiome composition in IBD patients in remission in relation to psychological well-being and quality of life. Further studies are warranted to gain more insight into the direction of this link and to investigate whether intestinal inflammation subsequent to microbial alterations or microbial metabolites itself may impair psychological well-being.
Introduction: Intravenous iron formulations have been approved in Europe and North America for the treatment of iron deficiency if oral iron is not tolerated or not efficacious. Recently-developed ...intravenous iron formulations exhibit specific physicochemical and immunological properties, with distinct bioavailability, efficacy and safety profiles. Area of Interest: intravenous iron formulations safety and tolerability were reviewed in the framework of a Swiss expert meeting. This work focused on the specificity of each compound with emphasis on the practical aspects of its use. Expert Opinion: Adverse reactions in response to iv formulations can be categorized into two main types: hypophosphataemia and hypersensitivity. Hypophosphatemia follows administration of ferric carboxymaltose at a higher rate in comparison to other formulations, but is mostly mild, transient and asymptomatic. However, the decrease in serum phosphate following repeated administration of iron preparations can affect bone health, particularly in patients at risk for osteomalacia. Severe hypersensitivity reactions are the most lifethreatening adverse reactions to intravenous iron supplementation. Iron (III)- isomaltoside 1000 seems to induce severe hypersensitivity more often (RR 5.6 - 16.2) than ferric carboxymaltose. Further studies are needed to address issues of long-term safety in high dose and prolonged administration of intravenous iron preparations in case of chronic diseases.
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