Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease.

OBJECTIVE: Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date. DESIGN: We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry. RESULTS: We demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix. CONCLUSION: HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.

[Cost of illness of inflammatory bowel disease in Germany]. / Krankheitskosten chronisch entzündlicher Darmerkrankungen in Deutschland.

INTRODUCTION: The prevalence of inflammatory bowel disease (IBD) in Germany is rising. Due to a disease onset at a young age, direct and indirect costs are important. The aim of the present study is to provide a comprehensive presentation of existing healthcare costs for these diseases in Germany and to compare them by inflation adjustments for 2018. MATERIAL AND METHODS: Performing a systematic literature search, monetary costs were extracted from German and English literature. Quality and relevance of the studies were assessed with a checklist. RESULTS: The average outpatient cost for inflammatory bowel disease amounts between 18 and 87 Euro/pat/30 days, the average inpatient cost was between 1026 and 9083 Euro/case. Depending on the type of calculation, biologicals cause different amounts of cost. Few data are available for direct medical 82 and 618 Euro/pat/30 days, direct non-medical 63 and 84 Euro/pat/30 days and indirect costs 463 and 3493 Euro/pat/30 days. The total costs are about 533 Euro/pat/30 days, related to one year 6485 Euro/pat. CONCLUSION: For the first time, it is possible to compare existing medical costs for IBD in Germany. Current studies feature very heterogeneous methods and study populations of IBD. Depending on the collective, the total costs are up to 6485 Euro/patient/year.

Thumb sucking or nail biting in childhood and adolescence is associated with an increased risk of Crohn's disease: results from a large case-control study.

BACKGROUND: The hygiene hypothesis suggests that a reduction in microbial exposure contributes to an impaired immune response later in life and increases the incidence of immune-mediated diseases such as inflammatory bowel diseases (IBD). Thumb sucking and nail biting are two early habits that modulate the oral microbiota composition and antigen load. OBJECTIVE: We hypothesized a lower risk of Crohn's disease (CD) and ulcerative colitis (UC) in adults with prior thumb sucking and nail biting. METHODS: 918 IBD cases and their 918 siblings without IBD were asked to fill out a survey containing 32 questions on environmental factors in childhood and early adulthood. Prevalence of thumb sucking and/or nail biting at the usually well-remembered time of (1) school enrollment and (2) coming-of-age ceremonies was the predefined combined risk factor of this study. RESULTS: 65% of the patients were female and 57% suffered from CD. About 49% of IBD patients but only 44% of their siblings reported thumb sucking/nail biting at the time of school enrollment or coming-of-age (p = .007). Sensitivity analysis revealed that this difference was observed in patients with CD (50% versus 41%; RR= 1.22; 95% CI 1.09-1.37, p = .001) but not in patients with UC (49% versus 48%; RR= 1.02; 95% CI 0.90-1.17; p = .83). CONCLUSION: Contrary to our expectation and challenging the hygiene hypothesis, we found that common oral habits are not protective against IBD. Instead, nail biting at the time of school enrollment and coming-of-age was a statistically significant risk factor for CD in our cohort. Key summary Evidence available before this study: The hygiene hypothesis suggests that a reduction in microbial exposure due to improved health activities has contributed to an immunological imbalance in the intestine and an increased incidence of allergic and autoimmune diseases. A population-based birth cohort study has demonstrated that thumb-sucking and nail biting in children lead to a reduction of the risk of atopic sensitization, asthma, and hay fever. Added value of this study: Contrary to the hypothesis, thumb sucking and nail biting were not associated with a reduced risk of IBD. Instead, thumb sucking and/or nail biting at the usually well-remembered points in time of school enrollment and of religious or secular coming-of-age ceremonies was associated with a higher risk of Crohn's disease but not of ulcerative colitis. Our data did not support the hygiene hypothesis, one pathogenic concept in the context of IBD.

Combination Treatment with Antibiotics and Glucocorticosteroids for Severe Ischemic Colitis.

BACKGROUND/AIMS: Ischemic colitis (IC) is most common in the elderly and patients with multiple comorbidities. It carries significant mortality. As yet no evidence-based therapeutic management exists. Aim of the study was to test therapeutic efficacy of a combination of prednisolone and antibiotics. METHODS: Prospective cohort study with retrospective analysis performed in a single teaching hospital in Germany. Consecutive patients with strict diagnostic criteria of severe IC, including colonoscopy, histology, and laboratory tests, were recruited. Main outcome measures were in-hospital mortality and number of operations counted within the hospital stay. Severity scores were calculated and biomarkers determined during the course of the hospital stay. RESULTS: A total of 342 patients with an International Classification of Diseases of IC were identified. About 151 patients met the diagnostic criteria and a total of 44 patients fulfilled all inclusion and exclusion criteria of severe IC and constituted the group of patients eligible for analysis. Five out of 44 patients (11.4%) died (in-hospital mortality). Surgery was performed in 3 patients (6.8%), 2 patients survived. The hospital stay lasted 14.0 ± 8.5 day and was significantly correlated with comorbidity (rs = 0.314, p = 0.038). No serious adverse events were observed. CONCLUSION: This is the first prospective study on therapeutic efficacy and safety in severe IC. The combination of intravenous antibiotics and intravenous prednisolone turned out to be safe and revealed promising efficacy.

Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms.

OBJECTIVE: Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. DESIGN: Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. RESULTS: We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p<0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3×10-10 and 0.002 (ORallelic=1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). CONCLUSION: In silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.

Budesonide Suppositories Are Effective and Safe for Treating Acute Ulcerative Proctitis.

BACKGROUND & AIMS: Although proctitis is the most limited form of ulcerative colitis, it causes unpleasant symptoms. Topical mesalamine, the standard treatment, is not always effective. We conducted a randomized phase 2 trial to determine the efficacy and safety of 2 doses of a budesonide suppository vs mesalamine suppositories vs combined budesonide and mesalamine suppositories for proctitis. METHODS: We performed a prospective, double-blind, double-dummy, multicenter trial in 337 patients with active proctitis to compare the efficacies of 4 different suppository treatments. Patients were randomly assigned to groups given 2 mg budesonide suppositories (2 mg BUS; n = 89 patients), 4 mg BUS (n = 79), 1 g mesalamine suppositories (1 g MES; n = 81), or the combination of 2 mg BUS and 1 g MES (n = 88). The study was performed from November 2013 through July 2015 at 36 study sites in Europe and Russia. The primary end point was the time to resolution of clinical symptoms, defined as the first of 3 consecutive days with a score of 0 for rectal bleeding and stool frequency. RESULTS: The mean time to resolution of symptoms in the 4 mg BUS (29.8 days) and combination of 2 mg BUS and 1 g MES (29.3 days) groups resembled that of the standard 1 g MES treatment (29.2 days), but was significantly longer in the 2 mg BUS group (35.5 days). Furthermore, proportions of patients with deep, clinical, and endoscopic remission, as well as mucosal healing, were similar among the 1 g MES, 4 mg BUS, and combination therapy groups, but significantly lower in the group that received 2 mg BUS. No safety signals were observed, and the patients' treatment acceptance was high (67%-85% of patients). CONCLUSIONS: In a multicenter randomized trial, we found that the efficacy and safety of 4 mg BUS in treatment of active proctitis did not differ significantly from those of 1 g MES. Budesonide suppositories offer an alternative therapy to mesalamine for topical treatment of proctitis. Clinicaltrialsregister.eu no: 2012-003362-41.

Granulomonocytapheresis as a cell-dependent treatment option for patients with inflammatory bowel disease: Concepts and clinical features for better therapeutic outcomes.

Ulcerative colitis (UC) and Crohn's disease (CD) are major phenotypes of the chronic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms. The chronic nature of IBD means that patients require life-long medications, and this may lead to drug dependency, loss of response together with adverse side effects as additional morbidity factors. The efficacy of antitumour necrosis factor (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation and perpetuation of IBD. However, cytokines are released by myeloid lineage leucocytes like the CD14+ CD16+ monocyte phenotype. Additionally in IBD, myeloid leucocytes are elevated with activation behavior, while lymphocytes are compromised. Therefore, patients' leucocytes appear logical targets of therapy. Adsorptive granulomonocytapheresis (GMA) with an Adacolumn uses carriers, which interact with the Fcγ receptor expressing leucocytes and deplete the elevated myeloid leucocytes, while the neutrophils, which re-enter the circulation via the Adacolumn outflow (≥40%) are phagocytosed by CD19 B-cells to become interleukin (IL)-10 producing Bregs or CD19high CD1Dhigh B-cells. IL-10 is an anti-inflammatory cytokine. GMA has been applied to treat patients with IBD. The efficacy outcomes have been impressive as well as disappointing, the clinical response to GMA defines the patients' disease course and severity at entry. Efficacy outcomes in patients with deep ulcers together with extensive loss of the mucosal tissue are not encouraging, while patients without these features respond well and attain a favorable long-term disease course. Accordingly, for responder patients, GMA fulfills a desire to be treated without drugs.

Development of an index to define overall disease severity in IBD.

BACKGROUND AND AIM: Disease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC. METHODS: Using a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute. RESULTS: For CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities. CONCLUSIONS: Based on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD.

Promises and Dangers of Combination Therapy.

The efficiency of the existing methods of treating inflammatory bowel disease (IBD) is limited. There are 2 ways to address this problem - either create new treatment modalities or optimize current therapies. Optimisation may be accomplished by using combinations of established therapeutic strategies. With regard to topically acting compounds such as 5-aminosalicylic acid, combining oral and rectal preparations is a commonly used method. Another commonly used combination is anti-tumor necrosis factor (TNF)-α antibody modalities together with immunosuppressants (thiopurines, methotrexate). Several aspects favour those combinations such as increased effectivity, prevention of immunogenicity and perhaps less adverse events. Currently, discussion on directly additive therapeutic effects is in progress, which have been demonstrated in some clinical trials. As on date, the combination of infliximab with azathioprine is most likely the most effective treatment of Crohn's disease. On the other hand, a combination therapy with both compounds affecting the immune system has, of course, risks. For sure, the frequency with which serious infectious complications are arising is increasing. Furthermore, the number of patients experiencing malignancies such as hepato-splenic lymphoma or melanoma is strongly suspected to be on the rise. In summary, combinations of current treatments for IBD are widely established. Various strategies have been studied and significant improvements of therapeutic effects have been demonstrated. Unfortunately, some of those proven combinations increase therapeutic risks, for example, increase the frequency of serious infections and also of some malignancies. Therefore, great caution has to be exercised when applying combination therapies.

German Guidelines.

Because of its frequency, diverticular disease is a burden on health care systems. Only few formal guidelines covering all aspects of the disease exist. Here, some selected statements from the German guidelines are given. The guidelines include significant recommendations for the diagnosis and management of diverticular disease. Both diagnosis and management depend definitely on clear definitions of the situation of an individual patient. Therefore, a new classification is proposed that is based on earlier suggestions. An internationally established classification would not only enable better patient care but could also lead to studies with comparable results.

Iron Deficiency, Zinc, Magnesium, Vitamin Deficiencies in Crohn's Disease: Substitute or Not?

Inflammatory bowel disease (IBD) is characterized by inflammatory reactions, complications, extraintestinal manifestations and a loss of intestinal functions, for example, failures of absorption and secretion. According to intestinal dysfunction, a wide array of pathogenetic pathways is existing leading to iron deficiency and numerous vitamins as well as trace element deficiencies. Complications, symptoms and signs of those deficiencies are common in IBD with varying degrees of clinical significance. This review focuses on selected micronutrients including iron, zinc, magnesium and some vitamins. Epidemiology with respect to IBD, pathophysiology, diagnosis and clinical aspects are addressed. Finally, some suggestions for treatment of deficient situations are discussed. In conclusion, some micronutrients have significant impact on complications and quality of life in IBD. Deficiencies may even influence the course of the disease. Those deficiencies should be thoroughly supplemented.

[Inflammatory Bowel Disease Competence Network]. / Kompetenznetz Darmerkrankungen.

The Inflammatory Bowel Disease Competence Network is a network of more than 500 physicians and scientists from university clinics, hospitals and gastroenterology practices. The focus extends from the two major forms of inflammatory bowel diseases, Crohn's disease and ulcerative colitis, into other chronic inflammatory conditions affecting the intestine, including coeliac disease and microscopic colitis. The network translates basic science discoveries (in particular in the molecular epidemiology research) into innovative diagnostics and therapy. Through its strong networking structures it supports a continuous process to improve quality and standardisation in patient care that is implemented in close interaction with European networks addressing this disease group.Optimisation of patient care based on scientifically proven evidence is a main focus of the network. Therefore, it supports and coordinates translational research and infrastructure projects that investigate aetiology, improvement of diagnostic methods, and development of new or improved use of established therapies. Members participate in various training projects, thus ensuring the rapid transfer of research results into clinical practice.The competence network cooperates with the main patient organisations to engage patients in all levels of activities. The network and the patient organisations have interest in promoting public awareness about the disease entities, because their importance and burden is underestimated in non-specialised medical fields and among the general public.

White-Light or Narrow-Band Imaging Colonoscopy in Surveillance of Ulcerative Colitis: A Prospective Multicenter Study.

BACKGROUND & AIMS: Early detection of neoplastic lesions is essential in patients with long-standing ulcerative colitis but the best technique of colonoscopy still is controversial. METHODS: We performed a prospective multicenter study in patients with long-standing ulcerative colitis. Two colonoscopies were performed in each patient within 3 weeks to 3 months. In white-light (WL) colonoscopy, stepwise random biopsy specimens (4 biopsy specimens every 10 cm), segmental random biopsies (2 biopsy specimens in 5 segments), and targeted biopsy specimens were taken. In NBI colonoscopy, segmental and targeted biopsy specimens were taken. The sequence of WL and NBI colonoscopy was randomized. RESULTS: In 36 of 159 patients enrolled (22.6%), 54 lesions with intraepithelial neoplasia (IN) were found (51 low-grade, 3 high-grade). In WL colonoscopy we found 11 IN in stepwise biopsy specimens, 4 in segmental biopsy specimens, and 15 in targeted biopsy specimens. In NBI colonoscopy 7 IN were detected in segmental biopsy specimens and 24 IN were detected in targeted biopsy specimens. Almost all IN were found with one technique alone (κ value of WL vs NBI, -0.86; P < .001). Statistically equivalent numbers of IN were found in NBI colonoscopy with targeted and segmental biopsy specimens as in WL colonoscopy with targeted and stepwise biopsy specimens, but with fewer biopsy specimens (11.9 vs 38.6 biopsy specimens, respectively; P < .001), and less withdrawal time was necessary (23 vs 13 min, respectively; P < .001). CONCLUSIONS: Stepwise biopsy specimens are indispensable in WL colonoscopy. The combination of targeted and segmental biopsy specimens in the NBI technique is as sensitive as targeted together with stepwise biopsy specimens in WL colonoscopy, but requires fewer biopsy specimens and less time. The highest sensitivity should be reached by combining the WL and NBI techniques by switching between the modes.

The effect of body weight on the severity and clinical course of ulcerative colitis.

PURPOSE: Obesity is a risk factor for inflammatory diseases such as nonalcoholic steatohepatitis, pancreatitis, and Crohn's disease. The effect of being overweight or obese on the severity and clinical course of ulcerative colitis (UC) was assessed in a retrospective analysis of data from 2000-2006. METHODS: Two hundred and two consecutive UC patients were categorized according to body mass index (BMI). Patient and disease characteristics were compared between BMI categories using chi-square or Kruskal-Wallis tests. The percentage of patients with active UC, complications, steroid therapy, or immunosuppressive therapy was calculated for each group, and matched pair analyses were performed. RESULTS: Ten patients (5%) were underweight, 111 (55%) were normal weight, 54 (26.7%) were overweight, and 27 (13.4%) were obese. Pancolitis was inversely related to weight. BMI was also inversely correlated to disease severity, with a significantly smaller proportion of years with chronic active disease among overweight subjects versus normal-weight subjects (17.6 versus 23.9%, p = 0.05). More overweight than normal-weight patients had no chronic active disease in any year (66 versus 49%, p = 0.06), and the proportion of years with disease complications was higher in normal weight than in overweight subjects (1.8 versus 0.4%, p = 0.08). Disease activity during 2000-2006 was higher for underweight versus normal-weight patients, and only 20% of underweight subjects had no hospital admission compared to 80% of normal-weight patients (p = 0.07). CONCLUSIONS: This first study to explore the influence of obesity on UC showed that high BMI had rather a favorable effect on the prognosis, whereas low BMI pointed to a more severe course of the disease.

Granulocyte/Monocyte Adsorptive Apheresis in Moderate to Severe Ulcerative Colitis--Effective or Not?

BACKGROUND AND AIMS: Adsorptive granulocyte/monocyte apheresis (GMA) has shown promising efficacy in the treatment of patients with ulcerative colitis (UC). But a sham-controlled study was negative. A post-hoc analysis of this trial may haul out patients responding to GMA. METHODS: A total of 168 UC patients with a disease activity (DAI) between 6 and 11 were enrolled in this study. Out of 168 patients, 112 received GMA and 56 sham apheresis. The basis for this post hoc analysis is the clinical study report issued by Otsuka America Pharmaceutical. RESULTS: Baseline histology was available for 165 patients. Only 38% (63 of 165) of patients showed microscopic erosion/ulceration (group P). The remaining 62% of patients did not show microscopic erosion/ulceration (group A). The patients in group P showed significantly higher DAI, flexible proctosigmoidoscopy score and neutrophil infiltration into the colonic mucosa than those in group A (p = 0.0132, p = 0.0243 and p < 0.0001, respectively). Likewise, group P patients had a significantly (p = 0.0275) higher remission rate (11 of 46; 23.9%) when treated with GMA than with sham procedure (0 of 17; 0%). CONCLUSIONS: Patients in group P who had more active UC than those in group A showed clear clinical efficacy in response to GMA. We believe that true DAI should be specified for further randomized controlled trials.

Diverticular disease: guidelines of the german society for gastroenterology, digestive and metabolic diseases and the german society for general and visceral surgery.

BACKGROUND: Diverticular disease is one of the most common disorders of the gastrointestinal tract. 28-45% of the population develop colonic diverticula, while about 25% suffer symptoms and about 5% complications. AIM: To create formal guidelines for diagnosis and management. METHODS: Six working groups with 44 participants analyzed key questions in subject areas assigned to them. Following a systematic literature search, 451 publications were included. Consensus was obtained by agreement within the working groups, two Delphi processes and a guideline conference. RESULTS: Targeted management of diverticular disease requires a classificatory diagnosis. A new classification was created. In addition to the clinical examination, intestinal ultrasound or computed tomography is the determining factor. Interval colonoscopy is recommended to exclude comorbidities. A low-fiber diet, obesity, lack of exercise, smoking and immunosuppression have an adverse impact on diverticulosis. This can lead to diverticulitis. Antibiotics are no longer recommended in uncomplicated diverticulitis if no risk factors such as immunosuppression are present. If close monitoring is ensured, uncomplicated diverticulitis can be treated on an outpatient basis. Complicated diverticulitis should be treated in hospital, involving broad-spectrum antibiotic therapy, where necessary abscess drainage, and surgery, if possible laparoscopically. In the case of chronic relapsing diverticulitis, the risk of perforation decreases with each episode, so that surgery is no longer recommended after the second episode but only following individual assessment. CONCLUSIONS: New findings on diverticular disease call into question the overuse of antibiotics and excessive indications for surgery. Targeted treatment requires a precise diagnosis and intensive interdisciplinary cooperation.

Prospective Evaluation of the Prediction Score for a Mild Course of Crohn's Disease (PreMiCC) in Newly Diagnosed Patients With Crohn's Disease: The PROGNOS Study.

BACKGROUND AND AIMS: The course of Crohn's disease (CD) is highly variable. The Prospektive Evaluation eines Score zur Vorhersage eines milden Verlaufsbei neu diagnostizierten Morbus Crohn-Patienten in gastroenterologischen Fachpraxen (PROGNOS) study aimed to determine the frequency of a mild disease course and validate a proposed prediction score. METHODS: The PROGNOS study is a prospective study of CD patients who were newly diagnosed and, except for 1 course of 5-aminosalicylic acid or steroids for ≤10 days, therapy-naïve. Among other predefined inclusion criteria, the initial diagnosis had to be made ≤6 weeks before enrollment. All inception cohort patients were diagnosed and screened consecutively in participating gastroenterology practices in Germany specialized in inflammatory bowel disease. All screened CD patients were scored and, if possible, included in the study for up to 5 years (NCT02193048). RESULTS: A total of 201 CD patients were included in the study (43.3% male; mean age 33 years, mean follow-up 38 months). Altogether, 29.5% of the patients had a mild course at 36 months. Among those with a score ≤2, therapy escalation at 36 months was necessary for only 24.2%, whereas in the group with a score >2, therapy escalation was necessary for 70.2% of patients. In the Kaplan-Meier curve showing time to therapy escalation in the 2 groups, there was a pronounced and statistically significant divergence of the curves starting at 3 months and extending to 48 months (P < .001). CONCLUSIONS: In this prospective study, about 30% of incident CD patients had a mild disease course. Our suggested PreMiCC (prediction score for a mild course of Crohn's disease) successfully predicted this.

In our study of newly diagnosed Crohn's disease patients, we found that around 30% had a mild disease course. We also successfully tested our proposed PreMiCC (prediction score for a mild course of Crohn's disease), which predicts this mild course.