Alcohol and cannabis consumption in patients with inflammatory bowel disease: prevalence, pattern of consumption and impact on the disease.

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.

Identification of a Potent, Selective, and Brain-Penetrant Rho Kinase Inhibitor and its Activity in a Mouse Model of Huntington's Disease.

The Rho kinase (ROCK) pathway is implicated in the pathogenesis of several conditions, including neurological diseases. In Huntington's disease (HD), ROCK is implicated in mutant huntingtin (HTT) aggregation and neurotoxicity, and members of the ROCK pathway are increased in HD mouse models and patients. To validate this mode of action as a potential treatment for HD, we sought a potent, selective, central nervous system (CNS)-penetrant ROCK inhibitor. Identifying a compound that could be dosed orally in mice with selectivity against other AGC kinases, including protein kinase G (PKG), whose inhibition could potentially activate the ROCK pathway, was paramount for the program. We describe the optimization of published ligands to identify a novel series of ROCK inhibitors based on a piperazine core. Morphing of the early series developed in-house by scaffold hopping enabled the identification of a compound exhibiting high potency and desired selectivity and demonstrating a robust pharmacodynamic (PD) effect by the inhibition of ROCK-mediated substrate (MYPT1) phosphorylation after oral dosing.

Effectiveness of golimumab in patients with ulcerative colitis: results of a real-life study in Switzerland.

BACKGROUND: Tumor necrosis factor (TNF) inhibitors have improved treatment of ulcerative colitis (UC), but loss of response remains a frequent problem. The anti-TNF agent, golimumab, was approved in Switzerland for the treatment of UC in 2014. This study aims to summarize the experience of golimumab in a real-world setting in Switzerland. METHODS: We analyzed real-world data from 1769 UC patients from the Swiss Inflammatory Bowel Disease Cohort (SIBDC) study and performed a chart review of golimumab-treated patients. We extracted the partial Mayo score at t0 (baseline), t1 (2-16 weeks), t2 (17-35 weeks), and t3 (36-89 weeks). The primary endpoint was clinical response at t1, defined as marked improvement in partial Mayo score and objective parameters. Clinical remission was defined as resolution of symptoms and normalization of objective parameters. RESULTS: Our chart review included 103 UC patients with golimumab treatment (5.8% of all SIBDC UC patients); only 16 (15.5%) were anti-TNF naïve. Sixty-three patients remained on golimumab (61.2%) after 180 days, 51 (44.7%) after 365 days, and 34 (33%) after 630 days after the start of treatment. Upon golimumab treatment, the partial Mayo score decreased from 4 [interquartile range (IQR): 2-6] at t0 to 2 (IQR: 0-4) at t1, 1 (IQR: 0-3.5) at t2, and 1 (IQR: 0-3) at t3 (p < 0.001 for all comparisons with t0). The primary endpoint, clinical response at t1, could be evaluated in 52 patients and was met in 15 individuals (28.8%). Clinical remission at t1 was observed in 8 out of 52 patients (15.4%). Golimumab was generally well tolerated, one patient developed meningitis. The most frequent reasons to stop treatment were primary and secondary non-response. CONCLUSION: Golimumab was used in 5.8% of Swiss UC patients, mainly in biologic-experienced individuals. Golimumab treatment was associated with a sustained reduction of symptoms and clinical response in approximately 30% of patients.[ClinicalTrials.gov identifier: NCT00488631].

Primary Hypogammaglobulinaemia with Inflammatory Bowel Disease-Like Features: An ECCO CONFER Multicentre Case Series.

BACKGROUND: Hypogammaglobulinaemia is a disorder characterized by low serum immunoglobulin levels and a high prevalence of gastrointestinal manifestations. In some cases, clinical and endoscopic features are indistinguishable from those of inflammatory bowel disease [IBD]. METHODS: This was a multicentre case series performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. RESULTS: This report includes 27 patients with primary hypogammaglobulinaemia and IBD-like features: 20 males and seven females, median age 45.6 years (interquartile range [IQR] 35.2-59). Crohn's disease-like features were noted in 23 patients, and four patients had ulcerative colitis-like features. The diagnosis of hypogammaglobulinaemia preceded a diagnosis of IBD-like features in 20 patients [median of 7 years prior, IQR 2.6-20.6 years], and followed the appearance of IBD-like features in seven cases [median of 1 year after, IQR 0.45-5.6 years]. Hypogammaglobulinaemia aetiologies were common variable immunodeficiency [66.6%], agammaglobulinaemia [7.4%], selective IgA-deficiency [11.1%], Good's syndrome [7.4%], IgG subclass deficiency with IgA deficiency [3.7%] and hyper-IgM [3.7%]. In addition to antibiotics and intravenous immunoglobulin [IVIG] for hypogammaglobulinaemia, 12 patients received IBD-related treatment including 5-aminosalicylate agents [two patients], corticosteroids [one patient], thiopurines [three patients], anti-tumour necrosis factor [four patients] and vedolizumab [two patients]. By the end of the follow-up (44.5 months [IQR 18-81]), 21/27 [77%] patients were in clinical remission. CONCLUSION: This case series describes IBD-like features in patients with hypogammaglobulinaemia. The diagnosis of IBD-like features mainly occurred after that of hypogammaglobulinaemia, with successful recovery in the majority of cases after appropriate treatment.

Acute Lower Gastrointestinal Bleeding in an Emergency Department and Performance of the SHA2PE Score: A Retrospective Observational Study.

Lower gastrointestinal bleeding (LGIB) is a frequent cause of emergency department (ED) consultation, leading to investigations but rarely to urgent therapeutic interventions. The SHA2PE score aims to predict the risk of hospital-based intervention, but has never been externally validated. The aim of our single-center retrospective study was to describe patients consulting our ED for LGIB and to test the validity of the SHA2PE score. We included 251 adult patients who consulted in 2017 for hematochezia of <24 h duration; 53% were male, and the median age was 54 years. The most frequent cause of LGIB was unknown (38%), followed by diverticular disease and hemorrhoids (14%); 20% had an intervention. Compared with the no-intervention group, the intervention group was 26.5 years older, had more frequent bleeding in the ED (47% vs. 8%) and more frequent hypotension (8.2% vs. 1.1%), more often received antiplatelet drugs (43% vs. 18%) and anticoagulation therapy (28% vs. 9.5%), more often had a hemoglobin level of <10.5 g/dl (49% vs. 6.2%) on admission, and had greater in-hospital mortality (8.2% vs. 0.5%) (all p < 0.05). The interventions included transfusion (65%), endoscopic hemostasis (47%), embolization (8.2%), and surgery (4%). The SHA2PE score predicted an intervention with sensitivity of 71% (95% confidence interval: 66-83%), specificity of 81% (74-86%), and positive and negative predictive values of 53% (40-65%) and 90% (84-95%), respectively. SHA2PE performance was inferior to that in the original study, with a 1 in 10 chance of erroneously discharging a patient for outpatient intervention. Larger prospective validation studies are needed before the SHA2PE score can be recommended to guide LGIB patient management in the ED.

Risk of Vaccine-Preventable Infections in Swiss Adults with Inflammatory Bowel Disease.

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.

Adherence to Recommendations and Quality of Endoscopic Colorectal Cancer Surveillance in Long-Standing Ulcerative Colitis.

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 <8 years, 13.8% between 8 and 10 years, and 47.4% >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.

Evaluation of 5-(Trifluoromethyl)-1,2,4-oxadiazole-Based Class IIa HDAC Inhibitors for Huntington's Disease.

Using an iterative structure-activity relationship driven approach, we identified a CNS-penetrant 5-(trifluoromethyl)-1,2,4-oxadiazole (TFMO, 12) with a pharmacokinetic profile suitable for probing class IIa histone deacetylase (HDAC) inhibition in vivo. Given the lack of understanding of endogenous class IIa HDAC substrates, we developed a surrogate readout to measure compound effects in vivo, by exploiting the >100-fold selectivity compound 12 exhibits over class I/IIb HDACs. We achieved adequate brain exposure with compound 12 in mice to estimate a class I/IIb deacetylation EC50, using class I substrate H4K12 acetylation and global acetylation levels as a pharmacodynamic readout. We observed excellent correlation between the compound 12 in vivo pharmacodynamic response and in vitro class I/IIb cellular activity. Applying the same relationship to class IIa HDAC inhibition, we estimated the compound 12 dose required to inhibit class IIa HDAC activity, for use in preclinical models of Huntington's disease.

Varicella zoster virus in inflammatory bowel disease patients: what every gastroenterologist should know.

Primary Varicella Zoster virus (VZV) infection results in varicella (chickenpox) while 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 has been highlighted by the emergence of JAK-inhibitors and their safety profile in this patient population such as tofacitinib for the treatment of ulcerative colitis (UC). The current pipeline of emerging therapies include 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.

[Management of gastrointestinal and hepatic diseases during the COVID-19 outbreak]. / Prise en charge des patients avec maladies digestives et hépatiques durant la pandémie COVID-19.

The current epidemic of SARS-CoV-2 infection poses new challenges in the management of patients with gastrointestinal or liver disease. Consultations with patients with chronic diseases should ideally be done via telemedicine and treatments administered at home if possible. The latter should be maintained in non-infected subjects to limit the risk of decompensation of their underlying disease. In the event of proven infection, immunomodulatory or biological treatments will tend to be reduced or discontinued unless the disease is in a severely active phase. Elective endoscopy should be postponed, and urgent procedures should be performed with appropriate personal protective equipment.

L'épidémie actuelle d'infection par le SARS-CoV-2 pose de nouveaux défis dans la prise en charge des patients avec pathologies gastroentérologique ou hépatologique. Les consultations avec les patients atteints de maladies chroniques devraient se faire idéalement par télémédecine et les traitements administrés à domicile si possible. Ces derniers doivent être maintenus chez les sujets non infectés pour limiter le risque de décompensation de leur maladie de base. En cas d'infection avérée, on aura tendance à diminuer voire interrompre les traitements immunomodulateurs ou biologiques sauf si la maladie est en phase sévèrement active. Les examens endoscopiques électifs doivent être reportés. Les interventions urgentes doivent être effectuées en appliquant des mesures de protection adéquates.

Toll-Interacting Protein Regulates Immune Cell Infiltration and Promotes Colitis-Associated Cancer.

Expression of Toll-interacting protein (Tollip), a potent TLR modulator, decreases in patients with inflammatory bowel diseases (IBD), whereas Tollip-/- mice are susceptible to colitis. Tollip expression was shown to be reduced in sporadic adenoma. In contrast, we found variable Tollip expression in patients with colitis-associated adenomas. In Tollip-/- mice challenged to develop colitis-associated cancer (CAC), tumor formation was significantly reduced owing to decreased mucosal proliferative and apoptotic indexes. This protection was associated with blunt inflammatory responses without significant changes in microbial composition. mRNA expression of Cd62l and Ccr5 homing receptors was reduced in colons of untreated Tollip-/- mice, whereas CD62L+ CD8+ T cells accumulated in the periphery. In Tollip-deficient adenomas Ctla-4 mRNA expression and tumor-infiltrating CD4+ Foxp3+ regulatory T cell (Treg) were decreased. Our data show that protection from CAC in Tollip-deficient mice is associated with defects in lymphocyte accumulation and composition in colitis-associated adenomas.

Vaccination in Patients with Inflammatory Bowel Diseases.

During the course of disease, a majority of inflammatory bowel disease (IBD) patients requires long-term immunosuppressive therapy with either immunomodulatory agents, biologics, or newer immunosuppressive therapies such as Vedolizumab, a selective α4ß7 inhibitor, Ustekinumab, an IL 12/23 p40 inhibitor, or the Janus kinase inhibitor Tofacitinib. Due to this, they are at increased risk for infectious diseases, many of which are possible to prevent by vaccination. This review focuses on recommended vaccinations in IBD patients and stresses special issues which have to be paid attention to. The aim of the review is to increase gastroenterologists' awareness of the importance of vaccination and to stress why especially the gastroenterologist should assess the vaccination status of the patient and initiate vaccination as soon as diagnosis is established.

Treatment Algorithm for Mild and Moderate-to-Severe Ulcerative Colitis: An Update.

BACKGROUND: Patient care in ulcerative colitis (UC) remains challenging despite an array of established treatment options and emerging new therapies. The management of UC therapy should be guided by the endoscopic extent of inflammation, disease severity, and prognostic factors of poor outcome. Complete remission, defined as durable symptomatic and endoscopic remission without corticosteroid therapy, is the desired treatment goal. SUMMARY: This review focuses on treatment recommendations for different clinical scenarios in moderate-to-severe UC: Active UC of any extent not responding to aminosalicylates, steroid-dependent UC, steroid-refractory UC, immunomodulator-refractory UC, and acute severe UC. Comprehensive treatment algorithms for daily clinical practice were developed based on published guidelines and current literature. Key Messages: While current treatment options including a number of biologicals and small molecules have evolved UC treatment to achieve sustained remission in a majority of patients, upcoming treatment options with different molecular pathways and different modes of actions will further increase the need for personalized medicine.

Therapeutic Drug Monitoring to Guide Clinical Decision Making in Inflammatory Bowel Disease Patients with Loss of Response to Anti-TNF: A Delphi Technique-Based Consensus.

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.

Evaluating the Cost-Effectiveness of Early Compared with Late or No Biologic Treatment to Manage Crohn's Disease using Real-World Data.

BACKGROUND AND AIMS: We evaluated the cost-effectiveness of early [≤2 years after diagnosis] compared with late or no biologic initiation [starting biologics >2 years after diagnosis or no biologic use] for adults with Crohn's disease in Switzerland. METHODS: We developed a Markov cohort model over the patient's lifetime, from the health system and societal perspectives. Transition probabilities, quality of life, and costs were estimated using real-world data. Propensity score matching was used to ensure comparability between patients in the early [intervention] and late/no [comparator] biologic initiation strategies. The incremental cost-effectiveness ratio [ICER] per quality-adjusted life year [QALY] gained is reported in Swiss francs [CHF]. Sensitivity and scenario analyses were performed. RESULTS: Total costs and QALYs were higher for the intervention [CHF384 607; 16.84 QALYs] compared with the comparator [CHF340 800; 16.75 QALYs] strategy, resulting in high ICERs [health system: CHF887 450 per QALY; societal: CHF449 130 per QALY]. In probabilistic sensitivity analysis, assuming a threshold of CHF100 000 per QALY, the probability that the intervention strategy was cost-effective was 0.1 and 0.25 from the health system and societal perspectives, respectively. In addition, ICERs improved when we assumed a 30% reduction in biologic prices [health system: CHF134 502 per QALY; societal: intervention dominant]. CONCLUSIONS: Early biologic use was not cost-effective, considering a threshold of CHF100 000 per QALY compared with late/no biologic use. However, early identification of patients likely to need biologics and future drug price reductions through increased availability of biosimilars may improve the cost-effectiveness of an early treatment approach.

Position statement on the use of biosimilars in inflammatory bowel disease.

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.

High Immunogenicity of the Pneumococcal Conjugated Vaccine in Immunocompromised Adults With Inflammatory Bowel Disease.

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.

Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance.

Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities. Owing to the growing use of ICIs in oncology, clinicians will increasingly be confronted with common but also rare irAEs; hence, awareness needs to be raised regarding the clinical presentation, diagnosis and management of these toxicities. In this Review, we provide an overview of the various types of irAEs that have emerged to date. We discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. We also highlight the most important aspects of the management of irAEs.

Publisher Correction: Microbial network disturbances in relapsing refractory Crohn's disease.

Owing to an error during typesetting, a number of references were deleted from the Methods reference list. This altered all of the references in the Methods section and some of the references in Extended Data Fig. 5, making them inaccurate. References 121-134 were added back into the Methods reference list, and the references in the Methods section and in Extended Data Fig. 5 were renumbered accordingly. The error has been corrected in the PDF and HTML versions of this article.

The Evolution of Health Care Utilisation and Costs for Inflammatory Bowel Disease Over Ten Years.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] places an economic strain on health systems due to expensive pharmaceutical therapy, risk of hospitalisation and surgery, and long-term monitoring. The evolving treatment guidelines advocate rapid scale-up to biologic agents in order to improve health outcomes and quality of life. This study evaluated changes in health care utilisation and expenditures for IBD in Switzerland over time. METHODS: We extracted clinical, patient, and resource consumption data from the Swiss IBD Cohort Study between 2006 and 2016. Average unit costs for IBD-related events were derived from Swiss claims data and pharmaceutical price lists. We used multivariate regression, controlling for patient-level characteristics, to estimate trends and determinants of direct and indirect costs and resource utilisation. RESULTS: We included 2365 adults diagnosed with Crohn's disease [CD; N = 1353] and ulcerative colitis [UC; N = 1012]. From 2006-16, mean health care expenditures per patient per year were 9504 euros [70% drugs, 23% inpatient, 7% outpatient] for CD and 5704 euros [68% drugs, 22% inpatient, 10% outpatient] for UC. Health care costs increased by 7% [CD] and 10% [UC] per year, largely due to rising pharmaceutical expenditures driven by increased biologic agent use. Inpatient, outpatient, and indirect costs fluctuated and did not offset increased pharmaceutical costs. Disease characteristics were important predictors of costs. CONCLUSIONS: Increased expenditure for IBD was marked by a shift towards greater pharmaceutical management over the past decade. This study highlights the need to identify cost-effective treatment strategies in the face of increased uptake and expenditures associated with innovative treatments.