| 1. |
- Holmgren, Johanna, et al.
(författare)
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The Risk of Serious Infections Before and After Anti-TNF Therapy in Inflammatory Bowel Disease : A Retrospective Cohort Study
- 2023
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press. - 1078-0998 .- 1536-4844. ; 19:3, s. 339-348
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Tidskriftsartikel (refereegranskat)abstract
- Lay Summary: The incidence rate of serious infection among inflammatory bowel disease patients did not increase with anti-TNF therapy compared with 1 year before treatment start. A decrease in incidence rate could be seen more than 1 year after initiation of anti-TNF.Background: Serious infections have been observed in patients with inflammatory bowel disease (IBD) on anti-TNF use-but to what extent these infections are due to anti-TNF or the disease activity per se is hard to disentangle. We aimed to describe how the rates of serious infections change over time both before and after starting anti-TNF in IBD.Methods: Inflammatory bowel disease patients naive to anti-TNF treatment were identified at 5 centers participating in the Swedish IBD Quality Register, and their medical records examined in detail. Serious infections, defined as infections requiring in-patient care, the year before and after the start of anti-TNF treatment were evaluated.Results: Among 980 patients who started their first anti-TNF therapy between 1999 and 2016, the incidence rate of serious infections was 2.19 (95% CI,1.43-3.36) per 100 person years the year before and 2.11 (95% CI, 1.33-3.34) per 100 person years 1 year after treatment start. This corresponded to an incidence rate ratio 1 year after anti-TNF treatment of 0.97 (95% CI, 0.51-1.84). Compared with before anti-TNF therapy, the incidence of serious infection was significantly decreased more than 1 year after treatment (incidence rate ratio 0.56; 95% CI, 0.33-0.95; P = .03).Conclusions: In routine clinical practice in Sweden, the incidence rate of serious infection among IBD patients did not increase with anti-TNF therapy. Instead, serious infections seemed to decrease more than 1 year after initiation of anti-TNF treatment.
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| 2. |
- Khalili, Hamed, et al.
(författare)
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Healthcare use, work loss and total costs in incident and prevalent Crohn's disease and ulcerative colitis : results from a nationwide study in Sweden
- 2020
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Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 52:4, s. 655-668
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are limited data on population-wide assessment of cost in Crohn's disease (CD) and ulcerative colitis (UC).Aim: To estimate the societal cost of actively treated CD and UC in Sweden.Methods: We identified 10 117 prevalent CD and 19 762 prevalent UC patients, aged ≥18 years on 1 January 2014 and 4028 adult incident CD cases and 8659 adult incident UC cases (2010-2013) from Swedish Patient Register. Each case was matched to five population comparators. Healthcare costs were calculated from medications, outpatient visits, hospitalisations and surgery. Cost of productivity losses was derived from disability pension and sick leave.Results: The mean annual societal costs per working-age patient (18-64 years) with CD and UC were $22 813 (vs $7533 per comparator) and $14 136 (vs $7351 per comparator) respectively. In patients aged ≥65 years, the mean annual costs of CD and UC were $9726 and $8072 vs $3875 and $4016 per comparator respectively. The majority of cost for both CD (56%) and UC (59%) patients originated from productivity losses. Higher societal cost of working-age CD patients as compared to UC patients was related to greater utilisation of anti-TNF (22.2% vs 7.4%) and increased annual disability pension (44 days vs 25 days). Among incident CD and UC patients, the mean total cost over the first year per patient was over three times higher than comparators.Conclusion: In Sweden, the societal cost of incident and prevalent CD and UC patients was consistently two to three times higher than the general population.
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| 3. |
- Jakobsson, G. L., et al.
(författare)
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Validating inflammatory bowel disease (IBD) in the Swedish National Patient Register and the Swedish Quality Register for IBD (SWIBREG)
- 2017
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 52:2, s. 216-221
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Tidskriftsartikel (refereegranskat)abstract
- Background: Both the Swedish National Patient Register (NPR) and the Swedish Quality Register for inflammatory bowel disease (IBD, SWIBREG) are important sources of research data and information. However, the validity of a diagnosis of IBD in these registers is unknown. Methods: Medical charts of 129 randomly selected patients from the NPR and 165 patients registered both in SWIBREG and the NPR were reviewed. Patients were classified according to standardized criteria for ulcerative colitis (UC), Crohn's disease (CD), or IBD unclassified (IBD-U). Positive predictive values (PPVs) for UC, CD, IBD-U (only SWIBREG), or having any form of IBD were then calculated. Results: For cases with >= 2 diagnoses of IBD in the NPR (hospitalizations or non-primary care outpatient visits), the PPV was 93% (95% CI: 87-97) for any IBD, 79% (66-88) for UC and 72% (60-82) for CD. In UC patients with >= 2 UC diagnoses but never a CD diagnosis, the PPV increased to 90% (77-97). The PPV for CD in patients with >= 2 CD diagnoses but never a UC diagnosis was 81% (67-91)). Combining data from SWIBREG (>= 1 record) and the NPR (>= 1 record), the PPV was 99% for any IBD (97-100), 96% (89-99) for UC, and 90% (82-96) for CD. Conclusion: The validity of the UC, CD, and IBD diagnoses is high in the NPR but even higher when cases were identified both in SWIBREG and the NPR. These results underline the need for a well-functioning Swedish Quality Register for IBD as a complement to the NPR.
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| 4. |
- Siekmann, Wiebke, 1978-, et al.
(författare)
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Surgical and not analgesic technique affects postoperative inflammation following colorectal cancer surgery : a prospective, randomized study
- 2017
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 19:6, s. 186-195
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Epidural analgesia reduces the surgical stress response. However, its effect on pro- and anti-inflammatory cytokines in the genesis of inflammation following major abdominal surgery remains unclear. Our main objective was to elucidate whether perioperative epidural analgesia prevents the inflammatory response following colorectal cancer surgery.METHODS: Ninety-six patients scheduled for open or laparoscopic surgery were randomized to epidural analgesia (group E) or patient-controlled intravenous analgesia (group P). Surgery and anaesthesia were standardized in both groups. Plasma cortisol, insulin and serum cytokines [interleukin 1β (IL-1β), IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumour necrosis factor α, interferon γ, granulocyte-macrophage colony-stimulating factor, prostaglandin E2 and vascular endothelial growth factor] were measured preoperatively (T0), 1-6 h postoperatively (T1) and 3-5 days postoperatively (T2). Mixed model analysis was used, after logarithmic transformation when appropriate, for analyses of cytokines and stress markers.RESULTS: >There were no significant differences in any serum cytokine concentration between groups P and E at any time point except for IL-10 which was 87% higher in group P [median and range 4.1 (2.3-9.2) pg/ml] compared to group E [2.6 (1.3-4.7) pg/ml] (P = 0.002) at T1. There was no difference in plasma cortisol and insulin between the groups at any time point after surgery. A significant difference in median serum cytokine concentration was found between open and laparoscopic surgery with higher levels of IL-6, IL-8 and IL-10 at T1 in patients undergoing open surgery compared to laparoscopic surgery. No difference in serum cytokine concentration was detected between the groups or between the surgical technique at T2.CONCLUSIONS: Open surgery, compared to laparoscopic surgery, has greater impact on these inflammatory mediators than epidural analgesia vs intravenous analgesia.
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| 5. |
- Eberhardson, M., et al.
(författare)
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Anti-TNF treatment in Crohn's disease and risk of bowel resection-a population based cohort study
- 2017
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Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 46:6, s. 589-598
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Tidskriftsartikel (refereegranskat)abstract
- 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 naive 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.
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| 6. |
- Gerdin, Linda, et al.
(författare)
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The Swedish Crohn Trial: A Prematurely Terminated Randomized Controlled Trial of Thiopurines or Open Surgery for Primary Treatment of Ileocaecal Crohns Disease
- 2016
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Ingår i: Journal of Crohn's & Colitis. - : OXFORD UNIV PRESS. - 1873-9946 .- 1876-4479. ; 10:1, s. 50-54
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The importance of efficient and safe treatment of Crohns disease is highlighted by its chronicity. Both medical and surgical treatments have shown good results in the symptomatic control of limited ileocaecal Crohns disease. The aim of this study was to compare medical treatment with surgical treatment of ileocaecal Crohns disease. Methods: Thirty-six patients from seven hospitals with primary ileocaecal Crohns disease were randomized to either medical or surgical treatment. The medical treatment was induction of remission with budesonide and thereafter maintenance treatment with azathioprine. The surgical treatment was open ileocaecal resection. Crohns disease activity index over time, expressed as area under the curve at 1, 3 and 5 years, was the primary endpoint. Subjective health measured with the 36-item Short Form Survey Instrument (SF36) and a visual analogue scale (VAS) were secondary endpoints. Results: There were no differences between the treatment groups in Crohns disease activity index over time. General health, measured as SF36 score, was higher in patients receiving surgical treatment than in those receiving medical treatment at 1 year, but there was no corresponding difference in VAS. Due to the slow inclusion rate and changes in clinical practice, the study was t = erminated prematurely. Conclusion: The study ended up being underpowered and should be interpreted with caution, but there was no clinically significant difference between the two treatment arms. Further studies are needed to address this important clinical question.
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| 7. |
- Alkaissi, Lina Y., et al.
(författare)
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Antagonism of Adherent Invasive E. coli LF82 With Human α-defensin 5 in the Follicle-associated Epithelium of Patients With Ileal Crohn’s Disease
- 2021
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Ingår i: Inflammatory Bowel Diseases. - : OXFORD UNIV PRESS INC. - 1078-0998 .- 1536-4844. ; 27:7, s. 1116-1127
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Tidskriftsartikel (refereegranskat)abstract
- Background: The first visible signs of Crohns disease (CD) are microscopic erosions over the follicle-associated epithelium (FAE). The aim of the study was to investigate the effects of human alpha-defensin 5 (HD5) on adherent-invasive Escherichia coli LF82 translocation and HD5 secretion after LF82 exposure in an in vitro model of human FAE and in human FAE ex vivo. Methods: An in vitro FAE-model was set up by the coculture of Raji B cells and Caco-2-cl1 cells. Ileal FAE from patients with CD and controls were mounted in Ussing chambers. The effect of HD5 on LF82 translocation was studied by LF82 exposure to the cells or tissues with or without incubation with HD5. The HD5 secretion was measured in human FAE exposed to LF82 or Salmonella typhimurium. The HD5 levels were evaluated by immunofluorescence, immunoblotting, and ELISA. Results: There was an increased LF82 translocation across the FAE-model compared with Caco-2-cl1 (P < 0.05). Incubation of cell/tissues with HD5 before LF82 exposure reduced bacterial passage in both models. Human FAE showed increased LF82 translocation in CD compared with controls and attenuated passage after incubation with sublethal HD5 in both CD and controls (P < 0.05). LF82 exposure resulted in a lower HD5 secretion in CD FAE compared with controls (P < 0.05), whereas Salmonella exposure caused equal secretion on CD and controls. There were significantly lower HD5 levels in CD tissues compared with controls. Conclusions: Sublethal HD5 reduces the ability of LF82 to translocate through FAE. The HD5 is secreted less in CD in response to LF82, despite a normal response to Salmonella. This further implicates the integrated role of antimicrobial factors and barrier function in CD pathogenesis.
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| 8. |
- Everhov, Åsa H., et al.
(författare)
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Increasing healthcare costs in inflammatory bowel disease 2007-2020 in Sweden
- 2023
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Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 58:7, s. 692-703
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Inflammatory bowel disease has been linked to increasing healthcare costs, but longitudinal data on other societal costs are scarce.AIM: To assess costs, including productivity losses, in patients with prevalent Crohn's disease (CD) or ulcerative colitis (UC) in Sweden between 2007 and 2020.METHODS: We linked data from national registers on all patients with CD or UC and a matched (sex, birthyear, healthcare region and education) reference population. We assessed mean costs/year in Euros, inflation-adjusted to 2020, for hospitalisations, out-patient visits, medications, sick leave and disability pension. We defined excess costs as the mean difference between patients and matched comparators.RESULTS: Between 2007 and 2020, absolute mean annual societal costs in working-age (18-64 years) individuals decreased by 17% in CD (-24% in the comparators) and by 20% in UC (-27% in comparators), due to decreasing costs from sick leave and disability, a consequence of stricter sick leave regulations. Excess costs in 2007 were dominated by productivity losses. In 2020, excess costs were mostly healthcare costs. Absolute and excess costs increased in paediatric and elderly patients. Overall, costs for TNF inhibitors/targeted therapies increased by 274% in CD and 638% in UC, and the proportion treated increased from 5% to 26% in CD, and from 1% to 10% in UC.CONCLUSION: Between 2007 and 2020, excess costs shifted from productivity losses to direct healthcare costs; that is, the patients' compensation for sickness absence decreased, while society increased its spending on medications. Medication costs were driven both by expanding use of TNF inhibitors and by high costs for newer targeted therapies.
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| 9. |
- Eberhardson, Michael, et al.
(författare)
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Tumour necrosis factor inhibitors in Crohn's disease and the effect on surgery rates
- 2022
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 24:4, s. 470-483
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Surgery is an important therapeutic option for Crohn's disease. The need for first bowel surgery seems to have decreased with the introduction of tumour necrosis factor inhibitors (TNFi; adalimumab or infliximab). However, the impact of TNFi on the need for intestinal surgery in Crohn's disease patients irrespective of prior bowel resection is not known. The aim of this work is to compare the incidence of bowel surgery in Crohn's disease patients who remain on TNFi treatment versus those who discontinue it. Method: We performed a nationwide register-based observational cohort study in Sweden of all incident and prevalent cases of Crohn's disease who started first-line TNFi treatment between 2006 and 2017. Patients were categorized according to TNFi treatment retention less than or beyond 1 year. The study cohort was evaluated with regard to incidence of bowel surgery from 12 months after the first ever TNFi dispensation. Results: We identified 5003 Crohn's disease patients with TNFi exposure: 3748 surgery naïve and 1255 with bowel surgery prior to TNFi initiation. Of these patients, 7% (n = 353) were subjected to abdominal surgery during the first 12 months after the start of TNFi and were subsequently excluded from the main analysis. A majority (62%) continued TNFi for 12 months or more. Treatment with TNFi for less than 12 months was associated with a significantly higher surgery rate compared with patients who continued on TNFi for 12 months or more (hazard ratio 1.26, 95% CI 1.09–1.46; p = 0.002). Conclusion: Treatment with TNFi for less than 12 months was associated with a higher risk of bowel surgery in Crohn's disease patients compared with those who continued TNFi for 12 months or more.
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| 10. |
- Shrestha, Sarita, 1991-, et al.
(författare)
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Association between inflammatory bowel disease and spondyloarthritis : findings from a nationwide study in Sweden
- 2022
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479 .- 1197-4982. ; 16:1, s. 1540-1550
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) has been associated with spondyloarthritis (SpA), but population-based estimates are scarce. Here we compare the occurrence of SpA before and after a diagnosis of IBD to the general population, overall and by IBD subtype and age.METHODS: We used a nationwide register-based cohort study of 39,203 patients diagnosed with IBD during 2006-2016, identified from Swedish registers and gastrointestinal biopsy data, and 390,490 matched reference individuals from the general population. Conditional logistic regression models were used to estimate odds ratios (ORs) for a prior (prevalent) SpA diagnosis and conditional Cox regression to calculate hazard ratios (HRs) for a subsequent (incident) SpA diagnosis in IBD patients.RESULTS: IBD patients were more likely to have prevalent SpA at IBD diagnosis (2.5%) compared to reference individuals (0.7%) with an OR of 3.48 (95%CI:3.23-3.75). They also more often received an incident diagnosis of SpA; during 23,341,934 person-years of follow-up in IBD patients, there were 1,030 SpA events (5.0/1,000 person-years) compared to 1,524 SpA events in the reference group (0.72/1,000 person-years), corresponding to an HR of 7.15 (95%CI:6.60-7.75). In subgroup analyses, associations were most pronounced among patients with Crohn's disease [(OR=5.20; 95%CI:4.59-5.89), and (HR=10.55; 95%CI:9.16-12.15)] and paediatric onset IBD [(OR=3.63; 95%CI:2.35-5.59) and (HR=15.03; 95%CI:11.01-20.53)].CONCLUSION: IBD patients more frequently experience SpA both before and after the diagnosis of IBD compared to the general population, supporting evidence of a shared pathophysiology. The variation in SpA comorbidity across IBD subtypes and age-groups, calls for targeted approaches to facilitate timely diagnosis and intervention.
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