Real-World Outcomes of Patients Starting Intravenous and Transitioning to Subcutaneous Vedolizumab in Inflammatory Bowel Disease.

BACKGROUND: Real-world data on starting intravenous (IV) vedolizumab (VDZ) and transitioning to subcutaneous (SC) treatment in inflammatory bowel disease (IBD) are scarce. AIMS: To assess treatment outcomes of patients with IBD starting IV VDZ and switching to SC VDZ in routine clinical care. METHODS: Adult patients with IBD switching from IV to SC VDZ treatment between 1 March 2020 and 31 December 2021 were identified from the Swedish IBD quality register. The primary outcome was SC VDZ persistence. Secondary outcomes included clinical remission, changes in quality of life (QoL) according to EuroQual 5-Dimensions 5-Levels (EQ-5D-5L) and the Short-Health Scale (SHS) and inflammatory markers, including faecal Calprotectin (FCP). RESULTS: Altogether, 406 patients with IBD (Crohn's disease, n = 181; ulcerative colitis, n = 225) were identified. After a median follow-up of 30 months from starting IV VDZ treatment, the persistence rates were 98%(178/181) in Crohn's disease and 94% (211/225) in ulcerative colitis. Most patients (84%) transitioned during maintenance therapy, and the median follow-up from switch to SC VDZ was 10 months. Compared to baseline, statistically significant improvements were observed in all domains of the SHS, EQ-5D index value and visual analogue scale. Median (interquartile range) FCP concentrations (µg/g) decreased from 459 (185-1001) to 65 (26-227) in Crohn's disease (n = 45; p < 0.001) and from 646 (152-1450) to 49 (20-275) in ulcerative colitis (n = 58; p < 0.001). CONCLUSION: Initiating IV VDZ and switching to SC treatment was associated with high persistence rates and improvements in measures of QoL and FCP. These findings are reassuring for patients who start IV VDZ and switch to SC VDZ.

Decrease in primary but not in secondary abdominal surgery for Crohn's disease: nationwide cohort study, 1990-2014.

BACKGROUND: Treatment of patients with Crohn's disease has evolved in recent decades, with increasing use of immunomodulatory medication since 1990 and biologicals since 1998. In parallel, there has been increased use of active disease monitoring. To what extent these changes have influenced the incidence of primary and repeat surgical resection remains debated. METHODS: In this nationwide cohort study, incident patients of all ages with Crohn's disease, identified in Swedish National Patient Registry between 1990 and 2014, were divided into five calendar periods of diagnosis: 1990-1995 and 1996-2000 with use of inpatient registries, 2001, and 2002-2008 and 2009-2014 with use of inpatient and outpatient registries. The cumulative incidence of first and repeat abdominal surgery (except closure of stomas), by category of surgical procedure, was estimated using the Kaplan-Meier method. RESULTS: Among 21 273 patients with Crohn's disease, the cumulative incidence of first abdominal surgery within 5 years of Crohn's disease diagnosis decreased continuously from 54·8 per cent in 1990-1995 to 40·4 per cent in 1996-2000 (P < 0·001), and again from 19·8 per cent in 2002-2008 to 17·3 per cent in 2009-2014 (P < 0·001). Repeat 5-year surgery rates decreased from 18·9 per cent in 1990-1995 to 16·0 per cent in 1996-2000 (P = 0·009). After 2000, no further significant decreases were observed. CONCLUSION: The 5-year rate of surgical intervention for Crohn's disease has decreased significantly, but the rate of repeat surgery has remained stable despite the introduction of biological therapy.

ANTECEDENTES: El tratamie nto de pacientes con enfermedad de Crohn ha evolucionado en las últimas décadas con un uso cada vez mayor de medicamentos inmunomoduladores desde 1990 y tratamientos biológicos desde 1998. Al mismo tiempo, ha aumentado la utilidad de la vigilancia activa de la enfermedad. Hasta qué punto estos cambios han influido en la incidencia de la resección quirúrgica primaria y repetida sigue siendo objeto de debate. MÉTODOS: Estudio de cohortes a nivel nacional de pacientes incidentes con enfermedad de Crohn de todas las edades identificados en el registro sueco nacional de pacientes entre 1990-2014, que se dividió en cinco períodos de diagnóstico: 1990-1995 y 1996-2000 con el uso de registros de pacientes hospitalizados, 2001, y 2002-2008 y 2009-2014 con uso de registros de pacientes ambulatorios y hospitalizados. Se estimó la incidencia acumulada de la primera cirugía abdominal y de las cirugías abdominales subsiguientes (excepto el cierre de estomas), por categoría de procedimiento quirúrgico, mediante el método de Kaplan-Meier. RESULTADOS: Entre 21.273 pacientes con enfermedad de Crohn, la incidencia acumulada de la primera cirugía abdominal durante los 5 años posteriores al diagnóstico de la enfermedad disminuyó continuamente del 54,8% en la cohorte 1990-1995 al 40,4% en la cohorte 1996-2000 (P < 0,001) y nuevamente del 19,8% en cohorte 2002-2008 al 17,3% en la cohorte 2009-2014 (P < 0,001). Las tasas cirugías iterativas a los 5 años disminuyeron de 18,9% en la cohorte 1990-1995 a 16,0% en la cohorte 1996-2000 (P = 0,017). Después del 2000, no se observaron más disminuciones significativas. CONCLUSIÓN: La tasa de intervención quirúrgica a los 5 años para la enfermedad de Crohn ha disminuido significativamente, pero la cirugía iterativa se ha mantenido estable a pesar de la introducción de la terapia biológica.

Incidence and lifetime risk of hospitalization and surgery for diverticular disease.

BACKGROUND: Studies on incidence rates of first-time colonic diverticular disease are few, and population-based estimates of lifetime risk are lacking. In this observational study, the incidence, admission rates and lifetime risks of hospitalization and surgery for diverticular disease were investigated. METHODS: Considering the entire Swedish population as an open cohort, incidence and admission rates, and lifetime risk estimates (considering death as a competing risk) of hospitalization and surgery for diverticular disease were calculated using data from cross-linked national registers and population statistics from 1987 to 2010. RESULTS: In total, there were 144 107 hospital admissions for diverticular disease in 95 049 individual patients. Of these, 17 599 were admissions with bowel resection or stoma formation in 16 824 patients. The total number of person-years in the population during the study period was 213 949 897. Age-standardized incidence rates were 47·4 (95 per cent c.i. 47·1 to 47·7) for first-time hospitalization with diverticular disease and 8·4 (8·2 to 8·5) per 100 000 person-years for diverticular disease surgery. The corresponding admission rates (including readmissions) were 70·8 (70·4 to 71·2) and 8·7 (8·6 to 8·9) per 100 000 person-years. Following an increase in 1990-1994, rates stabilized. Based on incidence and mortality rates from 2000 to 2010, the estimated remaining lifetime risk of hospitalization from 30 years of age was 3·1 per cent in men and 5·0 per cent in women. The corresponding risk of surgery was 0·5 per cent in men and 0·8 per cent in women. CONCLUSION: Diverticular disease is a common reason for hospital admission, particularly in women, but rates are stable and the lifetime risk of surgery is low.

Restorative surgery after colectomy for ulcerative colitis in England and Sweden: observations from a comparison of nationwide cohorts.

AIM: A longstanding disparity exists between the approaches to restorative surgery after colectomy for patients with ulcerative colitis (UC) in England and Sweden. This study aims to compare rates of colectomy and restorative surgery in comparable national cohorts. METHOD: The English Hospital Episode Statistics (HES) and Swedish National Patient Register (NPR) were interrogated between 2002 and April 2012. Patients with two diagnostic episodes for UC (age ≥ 15 years) were included. Patients were excluded if they had an episode of inflammatory bowel disease or colectomy before 2002. The cumulative incidences of colectomy and restorative surgery were calculated using the Kaplan-Meier method. RESULTS: A total of 98 691 patients were included in the study, 76 129 in England and 22 562 in Sweden. The 5-year cumulative incidence of all restorative surgery after colectomy in England was 33% vs 46% in Sweden (P-value < 0.001). Of the patients undergoing restorative surgery, 92.3% of English patients had a pouch vs 38.8% in Sweden and 7.7% vs 59.1% respectively had an ileorectal anastomosis (IRA). The 5-year cumulative incidence of colectomy in this study cohort was 13% in England and 6% in Sweden (P-value < 0.001). CONCLUSION: Following colectomy for UC only one-third of English patients and half of Swedish patients underwent restorative surgery. In England nearly all these patients underwent pouches, in Sweden a less significant majority underwent IRAs. It is surprising to demonstrate this discrepancy in a comparable cohort of patients from similar healthcare systems. The causes and consequences of this international variation in management are not fully understood and require further investigation.

Colectomy prior to diagnosis of primary sclerosing cholangitis is associated with improved prognosis in a nationwide cohort study of 2594 PSC-IBD patients.

BACKGROUND: Despite the close relationship between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), the association between colectomy and the prognosis of PSC remains controversial. AIM: To explore whether colectomy prior to PSC-diagnosis is associated with transplant-free survival. METHODS: A nationwide cohort study in Sweden including all patients aged 18 to 69 years in whom both PSC and IBD was diagnosed between 1987 and 2014 was undertaken. Each patient was followed from date of both PSC and IBD diagnoses until liver transplantation or death, or 31 December 2014. Patients with colon in situ, and colectomy prior to PSC-diagnosis were compared. Survival analyses were performed using the Kaplan-Meier method and multivariable Cox regression models. RESULTS: Of the 2594 PSC-IBD patients, 205 patients were treated with colectomy before PSC-diagnosis. During follow-up, liver transplantations were performed in 327 patients and 509 died. The risk of liver transplantation or death was lower in patients treated with colectomy prior to PSC-diagnosis (HR 0.71, 95% CI 0.53-0.95) than in patients with colon in situ. Male gender, longer time between IBD and PSC-diagnosis and older age were all associated with an increased risk of liver transplantation or death. Colectomy after PSC-diagnosis was however not associated with an increased risk of liver transplantation or death during long-term follow-up. CONCLUSIONS: In PSC-IBD patients, colectomy prior to PSC-diagnosis is associated with a decreased risk of liver transplantation or death.

Childhood onset inflammatory bowel disease and risk of cancer: a Swedish nationwide cohort study 1964-2014.

Objective To assess risk of cancer in patients with childhood onset inflammatory bowel disease in childhood and adulthood.Design Cohort study with matched general population reference individuals using multivariable Cox regression to estimate hazard ratios.Setting Swedish national patient register (both inpatient and non-primary outpatient care) 1964-2014.Participants Incident cases of childhood onset (<18 years) inflammatory bowel disease (n=9405: ulcerative colitis, n=4648; Crohn's disease, n=3768; unclassified, n=989) compared with 92 870 comparators from the general population matched for sex, age, birth year, and county.Main outcome measures Any cancer and cancer types according to the Swedish Cancer Register.Results During follow-up through adulthood (median age at end of follow-up 27 years), 497 (3.3 per 1000 person years) people with childhood onset inflammatory bowel disease had first cancers, compared with 2256 (1.5 per 1000 person years) in the general population comparators (hazard ratio 2.2, 95% confidence interval 2.0 to 2.5). Hazard ratios for any cancer were 2.6 in ulcerative colitis (2.3 to 3.0) and 1.7 in Crohn's disease (1.5 to 2.1). Patients also had an increased risk of cancer before their 18th birthday (2.7, 1.6 to 4.4; 20 cancers in 9405 patients, 0.6 per1000 person years). Gastrointestinal cancers had the highest relative risks, with a hazard ratio of 18.0 (14.4 to 22.7) corresponding to 202 cancers in patients with inflammatory bowel disease. The increased risk of cancer (before 25th birthday) was similar over time (1964-1989: 1.6, 1.0 to 2.4; 1990-2001: 2.3, 1.5 to 3.3); 2002-06: 2.9, 1.9 to 4.2; 2007-14: 2.2, 1.1 to 4.2).Conclusion Childhood onset inflammatory bowel disease is associated with an increased risk of any cancer, especially gastrointestinal cancers, both in childhood and later in life. The higher risk of cancer has not fallen over time.

Anti-TNF treatment in Crohn's disease and risk of bowel resection-a population based cohort study.

BACKGROUND: TNF inhibitors (TNFi) have been shown to reduce the need for surgery in Crohn's disease, but few studies have examined their effect beyond the first year of treatment. AIM: To conduct a register-based observational cohort study in Sweden 2006-2014 to investigate the risk of bowel resection in bowel surgery naïve TNFi-treated Crohn's disease patients and whether patients on TNFi ≥12 months are less likely to undergo bowel resection than patients discontinuing treatment before 12 months. METHODS: We identified all individuals in Sweden with Crohn's disease through the Swedish National Patient Register 1987-2014 and evaluated the incidence of bowel resection after first ever dispensation of adalimumab or infliximab from 2006 and up to 7 years follow-up. RESULTS: We identified 1856 Crohn's disease patients who had received TNFi. Among these patients, 90% treatment retention was observed at 6 months after start of TNFi and 65% remained on the drug after 12 months. The cumulative rates of surgery in Crohn's disease patients exposed to TNFi years 1-7 were 7%, 13%, 17%, 20%, 23%, 25% and 28%. Rates of bowel resection were similar between patients with TNFi survival <12 months and ≥12 months respectively (P=.27). No predictors (eg, sex, age, extension or duration of disease) for bowel resection were identified. CONCLUSIONS: The risk of bowel resection after start of anti-TNF treatment is higher in regular health care than in published RCTs. Patients on sustained TNFi treatment beyond 12 months have bowel resection rates similar to those who discontinue TNFi treatment earlier.

Prevalence of paediatric inflammatory bowel disease in Sweden: a nationwide population-based register study.

BACKGROUND: We evaluated the impact of different case definition algorithms on the prevalence of paediatric inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC) and to compare the occurrence of certain diseases compared to matched controls. METHODS: Paediatric patients (<18 years) were identified via ICD codes for UC and CD in Swedish registers between 1993 and 2010 (n = 1432). Prevalence was defined as ≥2 IBD-related visits. Prevalence of treated children in 2010 was defined as ≥2 IBD-related visits with one visit and ≥1 dispensed IBD-related drug prescription in 2010. To test the robustness of the estimates, prevalence was also calculated according to alternative case definitions. The presence of rheumatic, hepatobiliary, pancreatic, and dermatologic diseases were compared with age-/sex-/county-of-residence-matched general population controls. RESULTS: The IBD prevalence was 75/100,000 (CD: 29/100,000; UC: 30/100,000; patients with IBD-U: 16/100,000). Prevalence of treated disease in 2010 was 62/100,000 (CD: 23/100,000; UC: 25/100,000; patients with IBD-U: 13/100,000). When age restrictions were employed, the prevalence estimate decreased (<17y: 61/100,000, <16y: 49/100,000 and <15y: 38/100,000). Compared to general population controls (n = 8583), children with IBD had a higher prevalence of dermatologic (4.7% vs. 0.6%), hepatobiliary (including primary sclerosing cholangitis) (5.5% vs. 0.1%), pancreatic (1.7% vs. 0%) and rheumatic diseases (7.2% vs. 1.2%; all P < 0.01). CONCLUSIONS: The overall prevalence of paediatric IBD in Sweden was similar to that in earlier regional cohorts. IBD patients had a higher prevalence of comorbid conditions than matched general population controls.

Probability, rate and timing of reconstructive surgery following colectomy for inflammatory bowel disease in Sweden: a population-based cohort study.

AIM: Many patients with inflammatory bowel disease (IBD) need colectomy, but the rate of reconstructive surgery with restoration of intestinal continuity is unknown. The aim of this study was to investigate the probability, rate and timing of reconstructive surgery after colectomy in patients with IBD in a population-based setting. METHOD: The study cohort included all patients with IBD in Sweden who underwent colectomy from 2000 to 2009. Each patient was followed from admission for colectomy to admission for reconstructive surgery, date of death, migration or 31 December 2010. Kaplan-Meier survival curves and multivariable Poisson regression models were used to describe the probability, rate and timing of reconstructive surgery. RESULTS: Out of 2818 IBD patients treated with colectomy, 61.0% were male and 78.9% had ulcerative colitis. No reconstructive surgery had been performed in 1595 (56.6%) patients by the end of follow-up. Of the remaining 1223 patients, 526 underwent primary reconstructive surgery and 697 had a secondary reconstruction following a median interval of 357 days from primary surgery in the form of colectomy. The probability of reconstructive surgery was dependent on age (55.6% and 18.1% at ages 15-29 and ≥ 59 years, respectively), and the chance of reconstructive surgery was higher in hospitals that performed more than 13 colectomies for IBD per year [incidence rate ratio and 95% confidence interval 1.27 (1.09-1.49)]. CONCLUSION: Fewer than half of the patients having a colectomy for IBD underwent subsequent reconstructive surgery. Older age and low hospital volume were risk factors for no reconstructive surgery.

Allergy-related diseases and recurrent abdominal pain during childhood - a birth cohort study.

BACKGROUND: Allergy and immune dysregulation may have a role in the pathophysiology of recurrent abdominal pain of functional origin, but previous studies of allergy-related diseases and abdominal pain have contradictory results. AIM: To examine the association between allergy-related diseases or sensitisation during childhood and abdominal pain at age 12 years. METHODS: In this birth cohort study of 4089 children, parents answered questionnaires regarding asthma, allergic rhinitis, eczema and food hypersensitivity ('allergy-related diseases') at ages 0,1,2,4,8 and 12 years. Blood for analyses of allergen-specific IgE was sampled at 4 and 8 years. At 12 years, the children answered questions regarding abdominal pain. Children with coeliac disease or inflammatory bowel disease were excluded. Associations were examined using multivariable logistic regression. RESULTS: Among 2610 children with complete follow-up, 9% (n = 237) reported abdominal pain at 12 years. All allergy-related diseases were associated with concurrent abdominal pain at 12 years and the risk increased with increasing number of allergy-related diseases (P for trend <0.001). Asthma at 1 and 2 years and food hypersensitivity at 8 years were significantly associated with abdominal pain at 12 years. There was an increased risk of abdominal pain at 12 years in children sensitised to food allergens at 4 or 8 years, but in stratified analyses, this was confined to children whose parents had not reported food hypersensitivity at time of sensitisation. CONCLUSION: Allergy-related diseases as well as sensitisation to food allergens were associated with an elevated risk of abdominal pain, and the risk increased with the number of allergy-related diseases.

NPSR1 polymorphisms influence recurrent abdominal pain in children: a population-based study.

BACKGROUND: Recurrent abdominal pain (RAP) occurs frequently among children and is one of the cardinal symptoms of functional gastrointestinal disorders (FGID). The mechanisms of visceral pain and RAP are not fully understood. A heritable component has been demonstrated and a few candidate genes proposed. NPSR1 encodes the receptor for neuropeptide S (NPS) and NPS-NPSR1 signaling is involved in anxiety, inflammation, and nociception. NPSR1 polymorphisms are associated with asthma and chronic inflammatory diseases, but also with IBS-related intermediate phenotypes such as colonic transit time and rectal sensory ratings. Here, we sought to determine whether genetic variability in the NPSR1 gene influences the presence of RAP in children. METHODS: Twenty-eight single-nucleotide polymorphisms (SNPs) in the NPSR1 gene region were successfully genotyped in 1744 children from the Swedish birth cohort BAMSE. Questionnaire information was used to define RAP as episodes of abdominal pain occurring at least once a month in 12-year-olds. KEY RESULTS: The prevalence of RAP was 9% in BAMSE. Association with RAP was observed for seven NPSR1 SNPs, five of which withstood false discovery rate (FDR) correction for multiple testing (best p = 0.00054, OR: 1.55 for SNP rs2530566). The associated SNPs all map in a putative regulatory region upstream NPSR1, where they may exert their genetic effects through the modulation of gene expression. CONCLUSIONS & INFERENCES: Genetic variation at the NPSR1 locus impacts children's predisposition to RAP episodes in a Swedish population.

Use of antibiotics in infancy and childhood and risk of recurrent abdominal pain--a Swedish birth cohort study.

BACKGROUND: The etiology of recurrent abdominal pain of functional origin (AP) is largely unknown. Antibiotic treatment influences the intestinal microbiota, and a few studies have indicated an increased risk of AP in adults after antibiotic treatment. Corresponding data in children are lacking. The aim of this study was to explore the association between antibiotic treatment during childhood and AP at 12 years. METHODS: Two thousand seven hundred and thirty-two children from a Swedish, population-based birth cohort. Parents reported antibiotic use for the children between birth and 2 years. Antibiotic use between 9 and 12 years was collected from the Swedish Prescribed Drug Register. The children answered questionnaires regarding AP at age 12. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for AP at 12 years as a function of antibiotic use. KEY RESULTS: Antibiotic treatment between 9 and 12 years was not associated with AP at 12. Children who had received ≥3 courses, or broad-spectrum antibiotics between 9 and 12 years had an increased risk of AP at 12, but these associations failed to reach statistical significance. Antibiotic treatment during both the first and the second year of life increased the risk of AP in girls at 12 (OR 1.65; 95% CI: 1.09-2.49), but not in boys or the whole cohort. CONCLUSIONS & INFERENCES: Antibiotic treatment does not seem to be a major risk factor for AP at 12 years. However, we cannot exclude that repeated courses, especially to infant girls, or use of broad-spectrum antibiotics between 9 and 12 years may be associated with an increased risk of AP.

The genetic influence on diverticular disease--a twin study.

BACKGROUND: The contribution of hereditary factors to the development of diverticular disease (DD) of the colon is unknown. Prevalence and location of diverticula differ in Western world compared to in Asia and several case reports describing families with DD have been published. AIM: To assess the heritability of DD in a large population-based sample of twins. METHODS: The Swedish Twin Registry was cross-linked to the Swedish Inpatient Registry. All twins, born between 1886 and 1980 and not dead before 1969, with a discharge diagnosis of DD were identified. Twins with diagnoses of colon cancer, coeliac disease or non-infectious colitis were excluded to decrease bias. Co-twin odds ratio (OR), concordance rates and tetrachoric correlations were calculated for monozygotic (MZ) and same gender-dizygotic (SS-DZ) twins. Mx-analyses were used to estimate the relative contributions of genetic effects and environmental factors to susceptibility for DD. Calculations were based on both primary and secondary discharge diagnoses to provide estimates reflecting impact of severity of the disease. RESULTS: A total of 104,452 twins met the inclusion criteria. Of these, 2296 had a diagnosis of DD. The OR of developing the disease given one's co-twin was affected was 7.15 (95% CI: 4.82-10.61) for MZ and 3.20 (95% CI: 2.21-4.63) for SS-DZ twins. Similarly, concordance rates and tetrachoric correlations were higher in MZ than those in SS-DZ twins. The heritability was estimated to 40% and the non shared environmental effects to 60%. CONCLUSION: Genetic susceptibility is an important component, along with individual specific environmental factors, for the development of diverticular disease of the colon.

Coeliac disease and risk of sepsis.

OBJECTIVE: To examine the risk of subsequent sepsis in individuals with coeliac disease. DESIGN: We used Swedish national health registers to identify 15 325 individuals with a diagnosis of coeliac disease (1964-2003) and 14 494 inpatient reference individuals. Cox regression estimated the hazard ratios (HRs) for subsequent sepsis. RESULTS: Compared with inpatient reference individuals, individuals with coeliac disease were at increased risk of sepsis (HR = 1.6, 95% confidence interval (95% CI) = 1.2 to 1.9, p<0.001). The highest risk estimates were seen for pneumococcal sepsis (HR = 2.5, 95% CI = 1.2 to 5.1, p = 0.014). Individuals with coeliac disease diagnosed in childhood were not at increased risk of subsequent sepsis (HR = 1.0, 95% CI = 0.6 to 1.9, p = 0.908). When individuals with coeliac disease were compared with reference individuals from the general population, coeliac disease was associated with an increased risk of sepsis (HR = 2.6, 95% CI = 2.1 to 3.0, p<0.001). The HR for pneumococcal sepsis was 3.9 (95% CI = 2.2 to 7.0, p<0.001). In this comparison, children with coeliac disease were also at an increased risk of sepsis (HR = 1.8, 95% CI = 1.2 to 2.7, p = 0.003). CONCLUSION: This study showed a modestly increased risk of sepsis in patients with coeliac disease with the highest risk for pneumococcal sepsis. This risk increase was limited to those with coeliac disease diagnosed in adulthood. Potential explanations include hyposplenism, increased mucosal permeability and an altered composition of the intestinal glycocalyx in individuals with coeliac disease.