Search

Background Prospectively and systematically collected long-term real-world clinical data on ustekinumab (anti-interleukin-12/23) are still scarce. Aims To assess the long-term effectiveness of ustekinumab in patients with active Crohns disease (CD). Methods This is a prospective multicenter study of adult patients with CD initiating ustekinumab according to recommended doses at 20 Swedish hospitals. The primary outcome was clinical remission (Harvey-Bradshaw Index (HBI) <= 4 points) at weeks 52 and 104. Secondary outcomes included clinical response (>= 3-point-decrease in HBI among patients with initial HBI >= 5 points), treatment retention, and biomarkers (C-reactive protein (CRP), hemoglobin, fecal-calprotectin) at weeks 52 and 104 compared to baseline. We also reported Health-related Quality of Life (HRQoL) measures. Results Of 114 included patients, 107 (94%) had previously failed >= 1 and 58 (51%) >= 2 anti-tumor necrosis factor agents. Forty (35%) had failed anti-integrin agents. Ustekinumab retention rates at weeks 52 and 104 were 70% (n = 80/114) and 61% (n = 69/114), respectively. Clinical response was seen in 36% (n = 25/69) and 29% (n = 20/69) of the patients, and remission was achieved in 32% (n = 31/96) and 29% (n = 28/96) at weeks 52 and 104, respectively. Median HBI and CRP levels decreased significantly at both timepoints as compared to baseline. Significant improvements were also observed in HRQoL. Adverse events were reported in 11% (n = 13/114) of the patients, including five cases of severe adverse events. No malignancies were observed. Conclusions In this nationwide prospective real-world 104-week-follow-up study of adult patients with active CD, ustekinumab was associated with long-term clinical effectiveness and improvement in HRQoL measures when used in routine clinical care., Funding Agencies|Karolinska InstituteKarolinska Institutet; Janssen Cilag AB, Sweden

Background: Proactive therapeutic drug monitoring (TDM) is often challenged by long turnaround time when using enzyme-linked immunosorbent assays (ELISAs), especially when analyses are centralised. Point-of-care tests (POCTs) allow rapid assessments, but data on their agreement with existing in-house methodologies are scarce.Objective: To examine the agreement between a POCT by ProciseDx (San Diego, CA) and the most frequently used in-house ELISA for infliximab (IFX) quantification in Sweden.Methods: Serum samples were analysed using the in-house ELISA, Karolinska University Hospital, Stockholm, Sweden and a POCT by ProciseDx (San Diego, CA). Agreement was assessed and differences were examined.Results: Samples from 61 inflammatory bowel disease (IBD) patients were analysed with a median IFX concentration of 7.9 mu g/mL (interquartile range (IQR) 5.5-13) for the POCT and 7.9 mu g/mL (IQR 5.2-12) for the ELISA (Pearsons correlation coefficient = 0.95 (95% CI 0.92-0.97, p < .01)). A Passing-Bablok regression yielded an intercept of -0.44 and a slope of 1.09. The Bland-Altman plot showed a systemic bias of -0.77 mu g/mL (95% CI -0.18 to -1.4) between the methods. The upper limit of agreement was 3.7 (95% CI 2.7-4.8) (mu g/mL), whereas the lower limit agreement was -5.3 (95% CI -6.3 to -4.3) (mu g/mL). An excellent reliability was observed, intraclass correlation showed = 0.94 (95% CI 0.89-0.96, p < .0001). When defining IFX concentration as subtherapeutic (<3.0 mu g/mL), therapeutic (3.0-7.0 mu g/mL) or supratherapeutic (>7.0 mu g/mL) drug levels, Kappa statistics showed a substantial agreement (0.79).Conclusions: The POCT by ProciseDx (San Diego, CA) demonstrated a good agreement with the in-house ELISA, supporting its use for rapid IFX quantification., Funding Agencies|Rui Rodrigues, MD, Clinical Immunology and Transfusion Medicine, Karolinska University Hospital is acknowledged for providing support regarding method description of in-house IFX analysis.; Karolinska University Hospital

Background and Aims: Microscopic colitis [MC] is currently regarded as an inflammatory bowel disease that manifests as two subtypes: collagenous colitis [CC] and lymphocytic colitis [LC]. Whether these represent a clinical continuum or distinct entities is, however, an open question. Genetic investigations may contribute important insight into their respective pathophysiologies.Methods: We conducted a genome-wide association study [GWAS] meta-analysis in 1498 CC, 373 LC patients, and 13 487 controls from Europe and the USA, combined with publicly available MC GWAS data from UK Biobank and FinnGen [2599 MC cases and 552 343 controls in total]. Human leukocyte antigen [HLA] alleles and polymorphic residues were imputed and tested for association, including conditional analyses for the identification of key causative variants and residues. Genetic correlations with other traits and diagnoses were also studied.Results: We detected strong HLA association with CC, and conditional analyses highlighted the DRB1*03:01 allele and its residues Y26, N77, and R74 as key to this association (best p = 1.4 x 10(-23), odds ratio [OR] = 1.96). Nominally significant genetic correlations were detected between CC and pneumonia [r(g) = 0.77; p = 0.048] and oesophageal diseases [r(g) = 0.45, p = 0.023]. An additional locus was identified in MC GWAS analyses near the CLEC16A and RMI2 genes on chromosome 16 [rs35099084, p = 2.0 x 10(-8), OR = 1.31]. No significant association was detected for LC.Conclusion: Our results suggest CC and LC have distinct pathophysiological underpinnings, characterised by an HLA predisposing role only in CC. This challenges existing classifications, eventually calling for a re-evaluation of the utility of MC umbrella definitions., Funding Agencies|Swedish Research Council [VR 2017-02403]

Background: Inflammatory bowel disease [IBD] has been linked to an increased risk of colorectal neoplasia. However, the types and risks of specific polyp types in IBD are less clear. Methods: We identified 41 880 individuals with IBD (Crohns disease [CD: n = 12 850]; ulcerative colitis [UC]: n = 29 030]) from Sweden matched with 41 880 reference individuals. Using Cox regression, we calculated adjusted hazard ratios [aHRs] for neoplastic colorectal polyps [tubular, serrated/sessile, advanced and villous] defined by histopathology codes. Results: During follow-up, 1648 [3.9%] IBD patients and 1143 [2.7%] reference individuals had an incident neoplastic colorectal polyp, corresponding to an incidence rate of 46.1 and 34.2 per 10 000 person-years, respectively. This correlated to an aHR of 1.23 (95% confidence interval [CI] 1.12-1.35) with the highest HRs seen for sessile serrated polyps [8.50, 95% CI 1.10-65.90] and traditional serrated adenomas [1.72, 95% CI 1.02-2.91]. aHRs for colorectal polyps were particularly elevated in those diagnosed with IBD at a young age and at 10 years after diagnosis. Both absolute and relative risks of colorectal polyps were higher in UC than in CD [aHRs 1.31 vs 1.06, respectively], with a 20-year cumulative risk difference of 4.4% in UC and 1.5% in CD, corresponding to one extra polyp in 23 patients with UC and one in 67 CD patients during the first 20 years after IBD diagnosis. Conclusions: In this nationwide population-based study, there was an increased risk of neoplastic colorectal polyps in IBD patients. Colonoscopic surveillance in IBD appears important, especially in UC and after 10 years of disease., Funding Agencies|Crohns and Colitis Foundation; Judith & Stewart Colton Center for Autoimmunity; NIH NIDDK Diseases [K23DK124570]; Swedish Research Council [2020-02002]; Young Scholar Award from the Strategic Research Area Epidemiology Program at Karolinska Institutet; Stockholm County Council [ALF]; Karolinska Institutet [ALF]; FORTE Foundation; Swedish Cancer Foundation; American College of Gastroenterology Senior Research Award; Beker Foundation; American Cancer Society Mentored Research Scholar Grant; NIH [R00CA215314, U01CA261961]

Background Prospectively and systematically collected long-term real-world clinical data on ustekinumab (anti-interleukin-12/23) are still scarce. Aims To assess the long-term effectiveness of ustekinumab in patients with active Crohns disease (CD). Methods This is a prospective multicenter study of adult patients with CD initiating ustekinumab according to recommended doses at 20 Swedish hospitals. The primary outcome was clinical remission (Harvey-Bradshaw Index (HBI) <= 4 points) at weeks 52 and 104. Secondary outcomes included clinical response (>= 3-point-decrease in HBI among patients with initial HBI >= 5 points), treatment retention, and biomarkers (C-reactive protein (CRP), hemoglobin, fecal-calprotectin) at weeks 52 and 104 compared to baseline. We also reported Health-related Quality of Life (HRQoL) measures. Results Of 114 included patients, 107 (94%) had previously failed >= 1 and 58 (51%) >= 2 anti-tumor necrosis factor agents. Forty (35%) had failed anti-integrin agents. Ustekinumab retention rates at weeks 52 and 104 were 70% (n = 80/114) and 61% (n = 69/114), respectively. Clinical response was seen in 36% (n = 25/69) and 29% (n = 20/69) of the patients, and remission was achieved in 32% (n = 31/96) and 29% (n = 28/96) at weeks 52 and 104, respectively. Median HBI and CRP levels decreased significantly at both timepoints as compared to baseline. Significant improvements were also observed in HRQoL. Adverse events were reported in 11% (n = 13/114) of the patients, including five cases of severe adverse events. No malignancies were observed. Conclusions In this nationwide prospective real-world 104-week-follow-up study of adult patients with active CD, ustekinumab was associated with long-term clinical effectiveness and improvement in HRQoL measures when used in routine clinical care., Funding Agencies|Karolinska InstituteKarolinska Institutet; Janssen Cilag AB, Sweden

Background Prospectively and systematically collected long-term real-world clinical data on ustekinumab (anti-interleukin-12/23) are still scarce. Aims To assess the long-term effectiveness of ustekinumab in patients with active Crohns disease (CD). Methods This is a prospective multicenter study of adult patients with CD initiating ustekinumab according to recommended doses at 20 Swedish hospitals. The primary outcome was clinical remission (Harvey-Bradshaw Index (HBI) <= 4 points) at weeks 52 and 104. Secondary outcomes included clinical response (>= 3-point-decrease in HBI among patients with initial HBI >= 5 points), treatment retention, and biomarkers (C-reactive protein (CRP), hemoglobin, fecal-calprotectin) at weeks 52 and 104 compared to baseline. We also reported Health-related Quality of Life (HRQoL) measures. Results Of 114 included patients, 107 (94%) had previously failed >= 1 and 58 (51%) >= 2 anti-tumor necrosis factor agents. Forty (35%) had failed anti-integrin agents. Ustekinumab retention rates at weeks 52 and 104 were 70% (n = 80/114) and 61% (n = 69/114), respectively. Clinical response was seen in 36% (n = 25/69) and 29% (n = 20/69) of the patients, and remission was achieved in 32% (n = 31/96) and 29% (n = 28/96) at weeks 52 and 104, respectively. Median HBI and CRP levels decreased significantly at both timepoints as compared to baseline. Significant improvements were also observed in HRQoL. Adverse events were reported in 11% (n = 13/114) of the patients, including five cases of severe adverse events. No malignancies were observed. Conclusions In this nationwide prospective real-world 104-week-follow-up study of adult patients with active CD, ustekinumab was associated with long-term clinical effectiveness and improvement in HRQoL measures when used in routine clinical care., Funding Agencies|Karolinska InstituteKarolinska Institutet; Janssen Cilag AB, Sweden

BACKGROUND & AIMS: Earlier studies have provided varying risk estimates for lymphoma in patients with inflam-matory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD.METHODS: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation.RESULTS: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16-1.50) and UC (HR, 1.09; 95% CI, 1.00-1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02-0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naive to such drugs.CONCLUSIONS: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas., Funding Agencies|Swedish Medical Society grant [SLS-789611]; Strategiskt Forskningsomrade Young Scholar Award at Karolinska Institutet, Avtal om Laekarutbildning och Forskning (ALF) [20170720, 20190638]; Swedish Research Council [2020-02002]; Swedish Cancer Society; Stockholm County Council (ALF); Swedish Foundation for Strategic Research; Independent Research Fund Denmark; Forskningsradet for halsa, arbetsliv och valfard Foundation; Swedish Cancer Foundation

BACKGROUND & AIMS: Earlier studies have provided varying risk estimates for lymphoma in patients with inflam-matory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD.METHODS: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation.RESULTS: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16-1.50) and UC (HR, 1.09; 95% CI, 1.00-1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02-0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naive to such drugs.CONCLUSIONS: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas., Funding Agencies|Swedish Medical Society grant [SLS-789611]; Strategiskt Forskningsomrade Young Scholar Award at Karolinska Institutet, Avtal om Laekarutbildning och Forskning (ALF) [20170720, 20190638]; Swedish Research Council [2020-02002]; Swedish Cancer Society; Stockholm County Council (ALF); Swedish Foundation for Strategic Research; Independent Research Fund Denmark; Forskningsradet for halsa, arbetsliv och valfard Foundation; Swedish Cancer Foundation

Background Prospectively and systematically collected long-term real-world clinical data on ustekinumab (anti-interleukin-12/23) are still scarce. Aims To assess the long-term effectiveness of ustekinumab in patients with active Crohns disease (CD). Methods This is a prospective multicenter study of adult patients with CD initiating ustekinumab according to recommended doses at 20 Swedish hospitals. The primary outcome was clinical remission (Harvey-Bradshaw Index (HBI) <= 4 points) at weeks 52 and 104. Secondary outcomes included clinical response (>= 3-point-decrease in HBI among patients with initial HBI >= 5 points), treatment retention, and biomarkers (C-reactive protein (CRP), hemoglobin, fecal-calprotectin) at weeks 52 and 104 compared to baseline. We also reported Health-related Quality of Life (HRQoL) measures. Results Of 114 included patients, 107 (94%) had previously failed >= 1 and 58 (51%) >= 2 anti-tumor necrosis factor agents. Forty (35%) had failed anti-integrin agents. Ustekinumab retention rates at weeks 52 and 104 were 70% (n = 80/114) and 61% (n = 69/114), respectively. Clinical response was seen in 36% (n = 25/69) and 29% (n = 20/69) of the patients, and remission was achieved in 32% (n = 31/96) and 29% (n = 28/96) at weeks 52 and 104, respectively. Median HBI and CRP levels decreased significantly at both timepoints as compared to baseline. Significant improvements were also observed in HRQoL. Adverse events were reported in 11% (n = 13/114) of the patients, including five cases of severe adverse events. No malignancies were observed. Conclusions In this nationwide prospective real-world 104-week-follow-up study of adult patients with active CD, ustekinumab was associated with long-term clinical effectiveness and improvement in HRQoL measures when used in routine clinical care., Funding Agencies|Karolinska InstituteKarolinska Institutet; Janssen Cilag AB, Sweden

Background Surgery rates in patients with Crohns disease have decreased during the last few decades, and use of antitumor necrosis agents (anti-TNF) has increased. Whether these changes correlate with a decreased probability of stoma is unknown. The objective of this study was to investigate the incidence of stoma in patients with Crohns disease over time. Methods Through linkage of national registers, we identified patients who were diagnosed with Crohns disease in 2003-2014 and were followed through 2019. We compared formation and closure of stomas over the calendar periods of diagnosis (2003-2006, 2007-2010, and 2011-2014). Results In a nationwide cohort of 18,815 incident patients with a minimum 5 years of follow-up, 652 (3.5%) underwent formation of a stoma. This was mostly performed in conjunction with ileocolic resection (39%). The 5-year cumulative incidence of stoma formation was 2.5%, with no differences between calendar periods (P = .61). Less than half of the patients (44%) had their stoma reversed. Stomas were more common in elderly-onset compared with pediatric-onset disease: 5-year cumulative incidence 3.6% vs 1.3%. Ileostomies were most common (64%), and 24.5% of the patients who underwent stoma surgery had perianal disease at end of follow-up. Within 5 years of diagnosis, 0.8% of the incident patients had a permanent stoma, and 0.05% had undergone proctectomy. The time from diagnosis to start of anti-TNF treatment decreased over calendar periods (P < .001). Conclusions Despite increasing use of anti-TNF and a low rate of proctectomy, the cumulative incidence of stoma formation within 5 years of Crohns disease diagnosis has not decreased from 2003 to 2019., Funding Agencies|Karolinska Institutet (KI SOS); Bengt Ihre Research Foundation; Swedish Research Council; Strategic Research Area Epidemiology program at Karolinska Institutet; Stockholm County Council; Karolinska Institutet (ALF); Ostergotland County Council; Linkoping University (ALF); Bengt Ihre Research Fellowship

Background Prospectively and systematically collected long-term real-world clinical data on ustekinumab (anti-interleukin-12/23) are still scarce. Aims To assess the long-term effectiveness of ustekinumab in patients with active Crohns disease (CD). Methods This is a prospective multicenter study of adult patients with CD initiating ustekinumab according to recommended doses at 20 Swedish hospitals. The primary outcome was clinical remission (Harvey-Bradshaw Index (HBI) <= 4 points) at weeks 52 and 104. Secondary outcomes included clinical response (>= 3-point-decrease in HBI among patients with initial HBI >= 5 points), treatment retention, and biomarkers (C-reactive protein (CRP), hemoglobin, fecal-calprotectin) at weeks 52 and 104 compared to baseline. We also reported Health-related Quality of Life (HRQoL) measures. Results Of 114 included patients, 107 (94%) had previously failed >= 1 and 58 (51%) >= 2 anti-tumor necrosis factor agents. Forty (35%) had failed anti-integrin agents. Ustekinumab retention rates at weeks 52 and 104 were 70% (n = 80/114) and 61% (n = 69/114), respectively. Clinical response was seen in 36% (n = 25/69) and 29% (n = 20/69) of the patients, and remission was achieved in 32% (n = 31/96) and 29% (n = 28/96) at weeks 52 and 104, respectively. Median HBI and CRP levels decreased significantly at both timepoints as compared to baseline. Significant improvements were also observed in HRQoL. Adverse events were reported in 11% (n = 13/114) of the patients, including five cases of severe adverse events. No malignancies were observed. Conclusions In this nationwide prospective real-world 104-week-follow-up study of adult patients with active CD, ustekinumab was associated with long-term clinical effectiveness and improvement in HRQoL measures when used in routine clinical care., Funding Agencies|Karolinska InstituteKarolinska Institutet; Janssen Cilag AB, Sweden

Background: Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohns disease (CD active). Methods: Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways. Results: The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed. Conclusion: This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares., Funding Agencies|Swedish Foundation For Strategic Research; Julins Foundation; Bengt Ihre Fellowship; Wilhelm and Martina Lundgren foundation; Magtarmfonden; Svenska Laekarsaellskapet; Calder foundation; Samhaellet i Goeteborg (KVVS) foundation; Sahlgrenska Academy University of Gothenburg [RB13-016]; Medical Faculty at Uppsala University; Apotekare Hedberg foundation; Swedish Research Council [2021-3743]; Swedish state; Swedish government; ALF-agreement; Regional Executive Board, Region Vaestra Goetaland; [2018-02566]; [2019-01052]; [ALFGBG-932651]; [ALFGBG-722331]; [ALFGBG-723921]; [VGFOUREG-940815]

Background Surgery rates in patients with Crohns disease have decreased during the last few decades, and use of antitumor necrosis agents (anti-TNF) has increased. Whether these changes correlate with a decreased probability of stoma is unknown. The objective of this study was to investigate the incidence of stoma in patients with Crohns disease over time. Methods Through linkage of national registers, we identified patients who were diagnosed with Crohns disease in 2003-2014 and were followed through 2019. We compared formation and closure of stomas over the calendar periods of diagnosis (2003-2006, 2007-2010, and 2011-2014). Results In a nationwide cohort of 18,815 incident patients with a minimum 5 years of follow-up, 652 (3.5%) underwent formation of a stoma. This was mostly performed in conjunction with ileocolic resection (39%). The 5-year cumulative incidence of stoma formation was 2.5%, with no differences between calendar periods (P = .61). Less than half of the patients (44%) had their stoma reversed. Stomas were more common in elderly-onset compared with pediatric-onset disease: 5-year cumulative incidence 3.6% vs 1.3%. Ileostomies were most common (64%), and 24.5% of the patients who underwent stoma surgery had perianal disease at end of follow-up. Within 5 years of diagnosis, 0.8% of the incident patients had a permanent stoma, and 0.05% had undergone proctectomy. The time from diagnosis to start of anti-TNF treatment decreased over calendar periods (P < .001). Conclusions Despite increasing use of anti-TNF and a low rate of proctectomy, the cumulative incidence of stoma formation within 5 years of Crohns disease diagnosis has not decreased from 2003 to 2019., Funding Agencies|Karolinska Institutet (KI SOS); Bengt Ihre Research Foundation; Swedish Research Council; Strategic Research Area Epidemiology program at Karolinska Institutet; Stockholm County Council; Karolinska Institutet (ALF); Ostergotland County Council; Linkoping University (ALF); Bengt Ihre Research Fellowship

Background: Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohns disease (CD active). Methods: Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways. Results: The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed. Conclusion: This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares., Funding Agencies|Swedish Foundation For Strategic Research; Julins Foundation; Bengt Ihre Fellowship; Wilhelm and Martina Lundgren foundation; Magtarmfonden; Svenska Laekarsaellskapet; Calder foundation; Samhaellet i Goeteborg (KVVS) foundation; Sahlgrenska Academy University of Gothenburg [RB13-016]; Medical Faculty at Uppsala University; Apotekare Hedberg foundation; Swedish Research Council [2021-3743]; Swedish state; Swedish government; ALF-agreement; Regional Executive Board, Region Vaestra Goetaland; [2018-02566]; [2019-01052]; [ALFGBG-932651]; [ALFGBG-722331]; [ALFGBG-723921]; [VGFOUREG-940815]

Background Prospectively and systematically collected long-term real-world clinical data on ustekinumab (anti-interleukin-12/23) are still scarce. Aims To assess the long-term effectiveness of ustekinumab in patients with active Crohns disease (CD). Methods This is a prospective multicenter study of adult patients with CD initiating ustekinumab according to recommended doses at 20 Swedish hospitals. The primary outcome was clinical remission (Harvey-Bradshaw Index (HBI) <= 4 points) at weeks 52 and 104. Secondary outcomes included clinical response (>= 3-point-decrease in HBI among patients with initial HBI >= 5 points), treatment retention, and biomarkers (C-reactive protein (CRP), hemoglobin, fecal-calprotectin) at weeks 52 and 104 compared to baseline. We also reported Health-related Quality of Life (HRQoL) measures. Results Of 114 included patients, 107 (94%) had previously failed >= 1 and 58 (51%) >= 2 anti-tumor necrosis factor agents. Forty (35%) had failed anti-integrin agents. Ustekinumab retention rates at weeks 52 and 104 were 70% (n = 80/114) and 61% (n = 69/114), respectively. Clinical response was seen in 36% (n = 25/69) and 29% (n = 20/69) of the patients, and remission was achieved in 32% (n = 31/96) and 29% (n = 28/96) at weeks 52 and 104, respectively. Median HBI and CRP levels decreased significantly at both timepoints as compared to baseline. Significant improvements were also observed in HRQoL. Adverse events were reported in 11% (n = 13/114) of the patients, including five cases of severe adverse events. No malignancies were observed. Conclusions In this nationwide prospective real-world 104-week-follow-up study of adult patients with active CD, ustekinumab was associated with long-term clinical effectiveness and improvement in HRQoL measures when used in routine clinical care., Funding Agencies|Karolinska InstituteKarolinska Institutet; Janssen Cilag AB, Sweden

Background Surgery rates in patients with Crohns disease have decreased during the last few decades, and use of antitumor necrosis agents (anti-TNF) has increased. Whether these changes correlate with a decreased probability of stoma is unknown. The objective of this study was to investigate the incidence of stoma in patients with Crohns disease over time. Methods Through linkage of national registers, we identified patients who were diagnosed with Crohns disease in 2003-2014 and were followed through 2019. We compared formation and closure of stomas over the calendar periods of diagnosis (2003-2006, 2007-2010, and 2011-2014). Results In a nationwide cohort of 18,815 incident patients with a minimum 5 years of follow-up, 652 (3.5%) underwent formation of a stoma. This was mostly performed in conjunction with ileocolic resection (39%). The 5-year cumulative incidence of stoma formation was 2.5%, with no differences between calendar periods (P = .61). Less than half of the patients (44%) had their stoma reversed. Stomas were more common in elderly-onset compared with pediatric-onset disease: 5-year cumulative incidence 3.6% vs 1.3%. Ileostomies were most common (64%), and 24.5% of the patients who underwent stoma surgery had perianal disease at end of follow-up. Within 5 years of diagnosis, 0.8% of the incident patients had a permanent stoma, and 0.05% had undergone proctectomy. The time from diagnosis to start of anti-TNF treatment decreased over calendar periods (P < .001). Conclusions Despite increasing use of anti-TNF and a low rate of proctectomy, the cumulative incidence of stoma formation within 5 years of Crohns disease diagnosis has not decreased from 2003 to 2019., Funding Agencies|Karolinska Institutet (KI SOS); Bengt Ihre Research Foundation; Swedish Research Council; Strategic Research Area Epidemiology program at Karolinska Institutet; Stockholm County Council; Karolinska Institutet (ALF); Ostergotland County Council; Linkoping University (ALF); Bengt Ihre Research Fellowship

Background Epidemiological studies have shown inconsistent incidence rates (IRs) for inflammatory bowel disease (IBD). Aim To assess the incidence and temporal trends of IBD in Sweden. Methods Nationwide cohort study based on diagnostic codes for IBD and biopsy reports registered through the ESPRESSO cohort in 1990-2014. Age-specific and age-standardised IRs and cumulative incidence were calculated. Results Overall, we identified 65 908 cases of incident IBD: ulcerative colitis (UC, n = 38 261, 58%), Crohns disease (CD, n = 18 577, 28%) and IBD-U (n = 9070, 14%). During 1990-2014, the overall IRs per 100 000 person-years were 29.0 (95% CI: 27.3-30.7) for IBD, 16.9 (15.9-17.9) for UC, and 8.1 (7.7-8.6) for CD. For IBD-U, the IR was 5.2 (4.9-5.6) in 2002-2014. The annual incidence of IBD, UC and CD increased by approximately 7% per year between 1990 and 2001 (P < 0.001) and then decreased by 1%-2% per year from 2002 onwards (P < 0.001). IRs for IBD, UC and IBD-U were higher in males while the IR for CD was higher in females. The lifetime risk of IBD was about 2.5% for both sexes. Conclusions In Sweden, the incidence of IBD in all subtypes increased in 1990-2001 but has since declined. One in 40 individuals is expected to be diagnosed with IBD during their lifetime.

Background Epidemiological studies have shown inconsistent incidence rates (IRs) for inflammatory bowel disease (IBD). Aim To assess the incidence and temporal trends of IBD in Sweden. Methods Nationwide cohort study based on diagnostic codes for IBD and biopsy reports registered through the ESPRESSO cohort in 1990-2014. Age-specific and age-standardised IRs and cumulative incidence were calculated. Results Overall, we identified 65 908 cases of incident IBD: ulcerative colitis (UC, n = 38 261, 58%), Crohns disease (CD, n = 18 577, 28%) and IBD-U (n = 9070, 14%). During 1990-2014, the overall IRs per 100 000 person-years were 29.0 (95% CI: 27.3-30.7) for IBD, 16.9 (15.9-17.9) for UC, and 8.1 (7.7-8.6) for CD. For IBD-U, the IR was 5.2 (4.9-5.6) in 2002-2014. The annual incidence of IBD, UC and CD increased by approximately 7% per year between 1990 and 2001 (P < 0.001) and then decreased by 1%-2% per year from 2002 onwards (P < 0.001). IRs for IBD, UC and IBD-U were higher in males while the IR for CD was higher in females. The lifetime risk of IBD was about 2.5% for both sexes. Conclusions In Sweden, the incidence of IBD in all subtypes increased in 1990-2001 but has since declined. One in 40 individuals is expected to be diagnosed with IBD during their lifetime.

Background: Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohns disease (CD active). Methods: Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways. Results: The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed. Conclusion: This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares., Funding Agencies|Swedish Foundation For Strategic Research; Julins Foundation; Bengt Ihre Fellowship; Wilhelm and Martina Lundgren foundation; Magtarmfonden; Svenska Laekarsaellskapet; Calder foundation; Samhaellet i Goeteborg (KVVS) foundation; Sahlgrenska Academy University of Gothenburg [RB13-016]; Medical Faculty at Uppsala University; Apotekare Hedberg foundation; Swedish Research Council [2021-3743]; Swedish state; Swedish government; ALF-agreement; Regional Executive Board, Region Vaestra Goetaland; [2018-02566]; [2019-01052]; [ALFGBG-932651]; [ALFGBG-722331]; [ALFGBG-723921]; [VGFOUREG-940815]

Background Surgery rates in patients with Crohns disease have decreased during the last few decades, and use of antitumor necrosis agents (anti-TNF) has increased. Whether these changes correlate with a decreased probability of stoma is unknown. The objective of this study was to investigate the incidence of stoma in patients with Crohns disease over time. Methods Through linkage of national registers, we identified patients who were diagnosed with Crohns disease in 2003-2014 and were followed through 2019. We compared formation and closure of stomas over the calendar periods of diagnosis (2003-2006, 2007-2010, and 2011-2014). Results In a nationwide cohort of 18,815 incident patients with a minimum 5 years of follow-up, 652 (3.5%) underwent formation of a stoma. This was mostly performed in conjunction with ileocolic resection (39%). The 5-year cumulative incidence of stoma formation was 2.5%, with no differences between calendar periods (P = .61). Less than half of the patients (44%) had their stoma reversed. Stomas were more common in elderly-onset compared with pediatric-onset disease: 5-year cumulative incidence 3.6% vs 1.3%. Ileostomies were most common (64%), and 24.5% of the patients who underwent stoma surgery had perianal disease at end of follow-up. Within 5 years of diagnosis, 0.8% of the incident patients had a permanent stoma, and 0.05% had undergone proctectomy. The time from diagnosis to start of anti-TNF treatment decreased over calendar periods (P < .001). Conclusions Despite increasing use of anti-TNF and a low rate of proctectomy, the cumulative incidence of stoma formation within 5 years of Crohns disease diagnosis has not decreased from 2003 to 2019., Funding Agencies|Karolinska Institutet (KI SOS); Bengt Ihre Research Foundation; Swedish Research Council; Strategic Research Area Epidemiology program at Karolinska Institutet; Stockholm County Council; Karolinska Institutet (ALF); Ostergotland County Council; Linkoping University (ALF); Bengt Ihre Research Fellowship

Background Epidemiological studies have shown inconsistent incidence rates (IRs) for inflammatory bowel disease (IBD). Aim To assess the incidence and temporal trends of IBD in Sweden. Methods Nationwide cohort study based on diagnostic codes for IBD and biopsy reports registered through the ESPRESSO cohort in 1990-2014. Age-specific and age-standardised IRs and cumulative incidence were calculated. Results Overall, we identified 65 908 cases of incident IBD: ulcerative colitis (UC, n = 38 261, 58%), Crohns disease (CD, n = 18 577, 28%) and IBD-U (n = 9070, 14%). During 1990-2014, the overall IRs per 100 000 person-years were 29.0 (95% CI: 27.3-30.7) for IBD, 16.9 (15.9-17.9) for UC, and 8.1 (7.7-8.6) for CD. For IBD-U, the IR was 5.2 (4.9-5.6) in 2002-2014. The annual incidence of IBD, UC and CD increased by approximately 7% per year between 1990 and 2001 (P < 0.001) and then decreased by 1%-2% per year from 2002 onwards (P < 0.001). IRs for IBD, UC and IBD-U were higher in males while the IR for CD was higher in females. The lifetime risk of IBD was about 2.5% for both sexes. Conclusions In Sweden, the incidence of IBD in all subtypes increased in 1990-2001 but has since declined. One in 40 individuals is expected to be diagnosed with IBD during their lifetime.

Background: Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohns disease (CD active). Methods: Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways. Results: The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed. Conclusion: This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares., Funding Agencies|Swedish Foundation For Strategic Research; Julins Foundation; Bengt Ihre Fellowship; Wilhelm and Martina Lundgren foundation; Magtarmfonden; Svenska Laekarsaellskapet; Calder foundation; Samhaellet i Goeteborg (KVVS) foundation; Sahlgrenska Academy University of Gothenburg [RB13-016]; Medical Faculty at Uppsala University; Apotekare Hedberg foundation; Swedish Research Council [2021-3743]; Swedish state; Swedish government; ALF-agreement; Regional Executive Board, Region Vaestra Goetaland; [2018-02566]; [2019-01052]; [ALFGBG-932651]; [ALFGBG-722331]; [ALFGBG-723921]; [VGFOUREG-940815]

Background: Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohns disease (CD active). Methods: Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways. Results: The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed. Conclusion: This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares., Funding Agencies|Swedish Foundation For Strategic Research; Julins Foundation; Bengt Ihre Fellowship; Wilhelm and Martina Lundgren foundation; Magtarmfonden; Svenska Laekarsaellskapet; Calder foundation; Samhaellet i Goeteborg (KVVS) foundation; Sahlgrenska Academy University of Gothenburg [RB13-016]; Medical Faculty at Uppsala University; Apotekare Hedberg foundation; Swedish Research Council [2021-3743]; Swedish state; Swedish government; ALF-agreement; Regional Executive Board, Region Vaestra Goetaland; [2018-02566]; [2019-01052]; [ALFGBG-932651]; [ALFGBG-722331]; [ALFGBG-723921]; [VGFOUREG-940815]

Background Surgery rates in patients with Crohns disease have decreased during the last few decades, and use of antitumor necrosis agents (anti-TNF) has increased. Whether these changes correlate with a decreased probability of stoma is unknown. The objective of this study was to investigate the incidence of stoma in patients with Crohns disease over time. Methods Through linkage of national registers, we identified patients who were diagnosed with Crohns disease in 2003-2014 and were followed through 2019. We compared formation and closure of stomas over the calendar periods of diagnosis (2003-2006, 2007-2010, and 2011-2014). Results In a nationwide cohort of 18,815 incident patients with a minimum 5 years of follow-up, 652 (3.5%) underwent formation of a stoma. This was mostly performed in conjunction with ileocolic resection (39%). The 5-year cumulative incidence of stoma formation was 2.5%, with no differences between calendar periods (P = .61). Less than half of the patients (44%) had their stoma reversed. Stomas were more common in elderly-onset compared with pediatric-onset disease: 5-year cumulative incidence 3.6% vs 1.3%. Ileostomies were most common (64%), and 24.5% of the patients who underwent stoma surgery had perianal disease at end of follow-up. Within 5 years of diagnosis, 0.8% of the incident patients had a permanent stoma, and 0.05% had undergone proctectomy. The time from diagnosis to start of anti-TNF treatment decreased over calendar periods (P < .001). Conclusions Despite increasing use of anti-TNF and a low rate of proctectomy, the cumulative incidence of stoma formation within 5 years of Crohns disease diagnosis has not decreased from 2003 to 2019., Funding Agencies|Karolinska Institutet (KI SOS); Bengt Ihre Research Foundation; Swedish Research Council; Strategic Research Area Epidemiology program at Karolinska Institutet; Stockholm County Council; Karolinska Institutet (ALF); Ostergotland County Council; Linkoping University (ALF); Bengt Ihre Research Fellowship

Background Surgery rates in patients with Crohns disease have decreased during the last few decades, and use of antitumor necrosis agents (anti-TNF) has increased. Whether these changes correlate with a decreased probability of stoma is unknown. The objective of this study was to investigate the incidence of stoma in patients with Crohns disease over time. Methods Through linkage of national registers, we identified patients who were diagnosed with Crohns disease in 2003-2014 and were followed through 2019. We compared formation and closure of stomas over the calendar periods of diagnosis (2003-2006, 2007-2010, and 2011-2014). Results In a nationwide cohort of 18,815 incident patients with a minimum 5 years of follow-up, 652 (3.5%) underwent formation of a stoma. This was mostly performed in conjunction with ileocolic resection (39%). The 5-year cumulative incidence of stoma formation was 2.5%, with no differences between calendar periods (P = .61). Less than half of the patients (44%) had their stoma reversed. Stomas were more common in elderly-onset compared with pediatric-onset disease: 5-year cumulative incidence 3.6% vs 1.3%. Ileostomies were most common (64%), and 24.5% of the patients who underwent stoma surgery had perianal disease at end of follow-up. Within 5 years of diagnosis, 0.8% of the incident patients had a permanent stoma, and 0.05% had undergone proctectomy. The time from diagnosis to start of anti-TNF treatment decreased over calendar periods (P < .001). Conclusions Despite increasing use of anti-TNF and a low rate of proctectomy, the cumulative incidence of stoma formation within 5 years of Crohns disease diagnosis has not decreased from 2003 to 2019., Funding Agencies|Karolinska Institutet (KI SOS); Bengt Ihre Research Foundation; Swedish Research Council; Strategic Research Area Epidemiology program at Karolinska Institutet; Stockholm County Council; Karolinska Institutet (ALF); Ostergotland County Council; Linkoping University (ALF); Bengt Ihre Research Fellowship

Background Epidemiological studies have shown inconsistent incidence rates (IRs) for inflammatory bowel disease (IBD). Aim To assess the incidence and temporal trends of IBD in Sweden. Methods Nationwide cohort study based on diagnostic codes for IBD and biopsy reports registered through the ESPRESSO cohort in 1990-2014. Age-specific and age-standardised IRs and cumulative incidence were calculated. Results Overall, we identified 65 908 cases of incident IBD: ulcerative colitis (UC, n = 38 261, 58%), Crohns disease (CD, n = 18 577, 28%) and IBD-U (n = 9070, 14%). During 1990-2014, the overall IRs per 100 000 person-years were 29.0 (95% CI: 27.3-30.7) for IBD, 16.9 (15.9-17.9) for UC, and 8.1 (7.7-8.6) for CD. For IBD-U, the IR was 5.2 (4.9-5.6) in 2002-2014. The annual incidence of IBD, UC and CD increased by approximately 7% per year between 1990 and 2001 (P < 0.001) and then decreased by 1%-2% per year from 2002 onwards (P < 0.001). IRs for IBD, UC and IBD-U were higher in males while the IR for CD was higher in females. The lifetime risk of IBD was about 2.5% for both sexes. Conclusions In Sweden, the incidence of IBD in all subtypes increased in 1990-2001 but has since declined. One in 40 individuals is expected to be diagnosed with IBD during their lifetime.

Background Epidemiological studies have shown inconsistent incidence rates (IRs) for inflammatory bowel disease (IBD). Aim To assess the incidence and temporal trends of IBD in Sweden. Methods Nationwide cohort study based on diagnostic codes for IBD and biopsy reports registered through the ESPRESSO cohort in 1990-2014. Age-specific and age-standardised IRs and cumulative incidence were calculated. Results Overall, we identified 65 908 cases of incident IBD: ulcerative colitis (UC, n = 38 261, 58%), Crohns disease (CD, n = 18 577, 28%) and IBD-U (n = 9070, 14%). During 1990-2014, the overall IRs per 100 000 person-years were 29.0 (95% CI: 27.3-30.7) for IBD, 16.9 (15.9-17.9) for UC, and 8.1 (7.7-8.6) for CD. For IBD-U, the IR was 5.2 (4.9-5.6) in 2002-2014. The annual incidence of IBD, UC and CD increased by approximately 7% per year between 1990 and 2001 (P < 0.001) and then decreased by 1%-2% per year from 2002 onwards (P < 0.001). IRs for IBD, UC and IBD-U were higher in males while the IR for CD was higher in females. The lifetime risk of IBD was about 2.5% for both sexes. Conclusions In Sweden, the incidence of IBD in all subtypes increased in 1990-2001 but has since declined. One in 40 individuals is expected to be diagnosed with IBD during their lifetime.

Background Prospectively and systematically collected real-world data on the effectiveness of ustekinumab (anti-interleukin-12/23) for treating Crohns disease (CD) are still limited. Aim To assess the short-term real-world effectiveness of ustekinumab in Swedish patients with active CD. Methods Prospective multicentre study of adult CD patients initiating ustekinumab according to recommended doses at 20 hospitals, between January 2017 and November 2018. Data were collected through an electronic case report form (eCRF) linked to the Swedish Inflammatory Bowel Disease Registry (SWIBREG). The primary outcomes were clinical response (>= 3-point-decrease of Harvey-Bradshaw index (HBI)) and remission (HBI <= 4 points) at week 16. Secondary outcomes included C-reactive protein (CRP) and haemoglobin (Hb) at baseline compared to week 16. Results Of 114 included patients, 107 (94%) had failed >= 1 and 58 (51%) >= 2 biological agents (anti-tumour necrosis factor [aTNF] agents or vedolizumab). The 16-week ustekinumab retention rate was 105 (92%). Data on HBI at baseline were available for 96 patients. At week 16, response or remission was achieved in 38/96 (40%) patients (25/96 (26%) achieving clinical remission and 23/96 (24%) showing a clinical response). The median CRP concentration (N = 65) decreased from 6 to 4 mg/l (p = .006). No significant changes in Hb were observed. No incident malignancies or infections, requiring antibiotic treatment, were reported. Conclusions In this nation-wide prospective real-world study of adult patients with CD, ustekinumab was associated with clinical effectiveness when administered according to clinical practice and seemed to represent a safe treatment option., Funding Agencies|Janssen Cilag AB, Sweden

Background: Whether long-term effectiveness differs between anti-tumour necrosis factor (anti-TNF) agents is unknown. Aims: To examine drug survival of first-line anti-TNF agents and identify predictors of discontinuation. To reduce channelling bias, we also compared drug survival of the second anti-TNF. Methods: Biologic-naive patients (N = 955) recorded in the Swedish IBD Quality Register (SWIBREG) were examined. We used propensity score matching, comparing drug survival over up to three years of follow-up. Cox regression estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Results: In Crohns disease, discontinuation because of lack/loss of response was 32% [95%CI = 26%-38%] for infliximab versus 16% [95%CI = 11%-21%] for adalimumab. Infliximab [vs adalimumab; aHR = 1.96; 95%CI = 1.20-3.21] and colonic disease (L2) [vs no L2; aHR = 2.17; 95% CI = 1.26-3.75] were associated with higher discontinuation rates, whereas normalised CRP at three months [aHR = 0.40; 95% CI = 0.19-0.81] with a lower rate. Consistently, patients who switched from adalimumab to infliximab (vs infliximab to adalimumab) had earlier discontinuation (P = 0.04). Concomitant use of immunomodulators was associated with a lower adverse drug reaction-mediated discontinuation rate [aHR = 0.46; 95% CI = 0.28-0.77], in part explained by fewer infusion reactions [aHR = 0.27; 95% CI = 0.08-0.89]. In ulcerative colitis, the probability of discontinuation because of lack/loss of response was 40% [95% CI = 33%-47%] for infliximab versus 37% [95% CI = 21%-53%] for adalimumab. Disease duration >= 10 years [aHR = 0.25; 95% CI = 0.10-0.58] and normalised CRP after three months [aHR = 0.39; 95% CI = 0.18-0.84] were associated with lower discontinuation rates. Conclusions: Clinical characterisation of patients may aid decision-making on anti-TNF treatment. The consistently shorter drug survival for infliximab (vs adalimumab) in Crohns disease, suggests a potential difference between, Funding Agencies: Research committee in Region Örebro County [OLL-685891]; Swedish governments agreement on medical training and research (ALF) [OLL-929900, OLL-549221]

Background: Whether long-term effectiveness differs between anti-tumour necrosis factor (anti-TNF) agents is unknown. Aims: To examine drug survival of first-line anti-TNF agents and identify predictors of discontinuation. To reduce channelling bias, we also compared drug survival of the second anti-TNF. Methods: Biologic-naive patients (N = 955) recorded in the Swedish IBD Quality Register (SWIBREG) were examined. We used propensity score matching, comparing drug survival over up to three years of follow-up. Cox regression estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Results: In Crohns disease, discontinuation because of lack/loss of response was 32% [95%CI = 26%-38%] for infliximab versus 16% [95%CI = 11%-21%] for adalimumab. Infliximab [vs adalimumab; aHR = 1.96; 95%CI = 1.20-3.21] and colonic disease (L2) [vs no L2; aHR = 2.17; 95% CI = 1.26-3.75] were associated with higher discontinuation rates, whereas normalised CRP at three months [aHR = 0.40; 95% CI = 0.19-0.81] with a lower rate. Consistently, patients who switched from adalimumab to infliximab (vs infliximab to adalimumab) had earlier discontinuation (P = 0.04). Concomitant use of immunomodulators was associated with a lower adverse drug reaction-mediated discontinuation rate [aHR = 0.46; 95% CI = 0.28-0.77], in part explained by fewer infusion reactions [aHR = 0.27; 95% CI = 0.08-0.89]. In ulcerative colitis, the probability of discontinuation because of lack/loss of response was 40% [95% CI = 33%-47%] for infliximab versus 37% [95% CI = 21%-53%] for adalimumab. Disease duration >= 10 years [aHR = 0.25; 95% CI = 0.10-0.58] and normalised CRP after three months [aHR = 0.39; 95% CI = 0.18-0.84] were associated with lower discontinuation rates. Conclusions: Clinical characterisation of patients may aid decision-making on anti-TNF treatment. The consistently shorter drug survival for infliximab (vs adalimumab) in Crohns disease, suggests a potential difference between, Funding Agencies: Research committee in Region Örebro County [OLL-685891]; Swedish governments agreement on medical training and research (ALF) [OLL-929900, OLL-549221]

Objectives Clinical trials demonstrated that golimumab is effective in anti-TNF naive patients with ulcerative colitis. We aimed to assess the clinical effectiveness of golimumab in a real-world setting. Materials and methods This was a prospective cohort study, conducted at 16 Swedish hospitals. Data were collected using an electronic case report form. Patients with active ulcerative colitis, defined as Mayo endoscopic subscore >= 2 were eligible for inclusion. The primary outcomes were clinical effectiveness at 12 weeks and 52 weeks, i.e. response (defined as a decrease in Mayo score by >= 3 points or 30% from baseline) and remission (defined as a Mayo score of <= 2 with no individual subscores >1). Results Fifty patients were included. At study entry, 70% were previously exposed to anti-TNF, 16% to vedolizumab, and 96% to immunomodulators. The 12 and 52-week drug continuation rates were 37/50 (74%) and 23/50 (46%), respectively. The 12-week response rate was 14/50 (28%), the remission rate, 8/50 (16%) and the corresponding figures at week 52 were 13/50 (26%) and 10/50 (20%). Among patients who continued golimumab, the median Mayo score decreased from 7 (6-9) at baseline to 1 (0-5) at 52 weeks (p < .01) and the faecal calprotectin decreased from 862 (335-1759) mu g/g to 90 (34-169) mu g/g (p < .01). Clinical response at week 12 was highly predictive of clinical remission at week 52 (adjusted OR: 73.1; 95% CI: 4.5-1188.9). Conclusions The majority of golimumab treated patients represented a treatment refractory patient-group. Despite this, our results confirm that golimumab is an effective therapy in ulcerative colitis., Funding Agencies|MSD; Swedish governments agreement on medical training and research [OLL-836791, OLL-929900]

Background Prospectively and systematically collected real-world data on the effectiveness of ustekinumab (anti-interleukin-12/23) for treating Crohns disease (CD) are still limited. Aim To assess the short-term real-world effectiveness of ustekinumab in Swedish patients with active CD. Methods Prospective multicentre study of adult CD patients initiating ustekinumab according to recommended doses at 20 hospitals, between January 2017 and November 2018. Data were collected through an electronic case report form (eCRF) linked to the Swedish Inflammatory Bowel Disease Registry (SWIBREG). The primary outcomes were clinical response (>= 3-point-decrease of Harvey-Bradshaw index (HBI)) and remission (HBI <= 4 points) at week 16. Secondary outcomes included C-reactive protein (CRP) and haemoglobin (Hb) at baseline compared to week 16. Results Of 114 included patients, 107 (94%) had failed >= 1 and 58 (51%) >= 2 biological agents (anti-tumour necrosis factor [aTNF] agents or vedolizumab). The 16-week ustekinumab retention rate was 105 (92%). Data on HBI at baseline were available for 96 patients. At week 16, response or remission was achieved in 38/96 (40%) patients (25/96 (26%) achieving clinical remission and 23/96 (24%) showing a clinical response). The median CRP concentration (N = 65) decreased from 6 to 4 mg/l (p = .006). No significant changes in Hb were observed. No incident malignancies or infections, requiring antibiotic treatment, were reported. Conclusions In this nation-wide prospective real-world study of adult patients with CD, ustekinumab was associated with clinical effectiveness when administered according to clinical practice and seemed to represent a safe treatment option., Funding Agencies|Janssen Cilag AB, Sweden

Objectives Clinical trials demonstrated that golimumab is effective in anti-TNF naive patients with ulcerative colitis. We aimed to assess the clinical effectiveness of golimumab in a real-world setting. Materials and methods This was a prospective cohort study, conducted at 16 Swedish hospitals. Data were collected using an electronic case report form. Patients with active ulcerative colitis, defined as Mayo endoscopic subscore >= 2 were eligible for inclusion. The primary outcomes were clinical effectiveness at 12 weeks and 52 weeks, i.e. response (defined as a decrease in Mayo score by >= 3 points or 30% from baseline) and remission (defined as a Mayo score of <= 2 with no individual subscores >1). Results Fifty patients were included. At study entry, 70% were previously exposed to anti-TNF, 16% to vedolizumab, and 96% to immunomodulators. The 12 and 52-week drug continuation rates were 37/50 (74%) and 23/50 (46%), respectively. The 12-week response rate was 14/50 (28%), the remission rate, 8/50 (16%) and the corresponding figures at week 52 were 13/50 (26%) and 10/50 (20%). Among patients who continued golimumab, the median Mayo score decreased from 7 (6-9) at baseline to 1 (0-5) at 52 weeks (p < .01) and the faecal calprotectin decreased from 862 (335-1759) mu g/g to 90 (34-169) mu g/g (p < .01). Clinical response at week 12 was highly predictive of clinical remission at week 52 (adjusted OR: 73.1; 95% CI: 4.5-1188.9). Conclusions The majority of golimumab treated patients represented a treatment refractory patient-group. Despite this, our results confirm that golimumab is an effective therapy in ulcerative colitis., Funding Agencies|MSD; Swedish governments agreement on medical training and research [OLL-836791, OLL-929900]

Background Prospectively and systematically collected real-world data on the effectiveness of ustekinumab (anti-interleukin-12/23) for treating Crohns disease (CD) are still limited. Aim To assess the short-term real-world effectiveness of ustekinumab in Swedish patients with active CD. Methods Prospective multicentre study of adult CD patients initiating ustekinumab according to recommended doses at 20 hospitals, between January 2017 and November 2018. Data were collected through an electronic case report form (eCRF) linked to the Swedish Inflammatory Bowel Disease Registry (SWIBREG). The primary outcomes were clinical response (>= 3-point-decrease of Harvey-Bradshaw index (HBI)) and remission (HBI <= 4 points) at week 16. Secondary outcomes included C-reactive protein (CRP) and haemoglobin (Hb) at baseline compared to week 16. Results Of 114 included patients, 107 (94%) had failed >= 1 and 58 (51%) >= 2 biological agents (anti-tumour necrosis factor [aTNF] agents or vedolizumab). The 16-week ustekinumab retention rate was 105 (92%). Data on HBI at baseline were available for 96 patients. At week 16, response or remission was achieved in 38/96 (40%) patients (25/96 (26%) achieving clinical remission and 23/96 (24%) showing a clinical response). The median CRP concentration (N = 65) decreased from 6 to 4 mg/l (p = .006). No significant changes in Hb were observed. No incident malignancies or infections, requiring antibiotic treatment, were reported. Conclusions In this nation-wide prospective real-world study of adult patients with CD, ustekinumab was associated with clinical effectiveness when administered according to clinical practice and seemed to represent a safe treatment option., Funding Agencies|Janssen Cilag AB, Sweden

Background It is not known to what extent biologic treatment for IBD is captured in the Swedish Prescribed Drug Register (PDR) and the National Patient Register (NPR). Methods A cross-sectional study from July 2005 until 2017, comparing data on biologic treatment in the PDR and the NPR with medical records. We assessed the proportion of started treatment episodes in the medical records that were found in the PDR/NPR ever, within +/- one year and within +/- three months; for any biologic drug, per specific drug (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab), by calendar period (2005-2008, 2009-2012, and 2013-2017) and by study center. For adalimumab, we assessed the validity of end of treatment episodes. Results Medical records of 1361 patients and 2323 treatment episodes with any biologic were reviewed and 80.1% (95% CI: 78.4-81.7) were ever captured in the PDR/NPR in. A time window of +/- one year or +/- three months reduced the sensitivity to 63.3% (95% CI: 61.3-65.3) and 52.6% (95% CI: 50.5-54.6), respectively. The sensitivity was high (>85%) for the prescribed injection drugs adalimumab, golimumab, and ustekinumab for all time windows and for adalimumab end of treatment, while considerably lower for the infusion drugs infliximab and vedolizumab. Conclusions The PDR and the NPR are reliable data sources on treatment with injection biologics in patients with IBD in Sweden. Infliximab and vedolizumab are poorly captured, why PDR/NPR data should only be used after careful consideration of their limitations or complemented by other data sources, e.g., the disease-specific quality register SWIBREG.

Background It is not known to what extent biologic treatment for IBD is captured in the Swedish Prescribed Drug Register (PDR) and the National Patient Register (NPR). Methods A cross-sectional study from July 2005 until 2017, comparing data on biologic treatment in the PDR and the NPR with medical records. We assessed the proportion of started treatment episodes in the medical records that were found in the PDR/NPR ever, within +/- one year and within +/- three months; for any biologic drug, per specific drug (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab), by calendar period (2005-2008, 2009-2012, and 2013-2017) and by study center. For adalimumab, we assessed the validity of end of treatment episodes. Results Medical records of 1361 patients and 2323 treatment episodes with any biologic were reviewed and 80.1% (95% CI: 78.4-81.7) were ever captured in the PDR/NPR in. A time window of +/- one year or +/- three months reduced the sensitivity to 63.3% (95% CI: 61.3-65.3) and 52.6% (95% CI: 50.5-54.6), respectively. The sensitivity was high (>85%) for the prescribed injection drugs adalimumab, golimumab, and ustekinumab for all time windows and for adalimumab end of treatment, while considerably lower for the infusion drugs infliximab and vedolizumab. Conclusions The PDR and the NPR are reliable data sources on treatment with injection biologics in patients with IBD in Sweden. Infliximab and vedolizumab are poorly captured, why PDR/NPR data should only be used after careful consideration of their limitations or complemented by other data sources, e.g., the disease-specific quality register SWIBREG.

Background: Whether long-term effectiveness differs between anti-tumour necrosis factor (anti-TNF) agents is unknown. Aims: To examine drug survival of first-line anti-TNF agents and identify predictors of discontinuation. To reduce channelling bias, we also compared drug survival of the second anti-TNF. Methods: Biologic-naive patients (N = 955) recorded in the Swedish IBD Quality Register (SWIBREG) were examined. We used propensity score matching, comparing drug survival over up to three years of follow-up. Cox regression estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Results: In Crohns disease, discontinuation because of lack/loss of response was 32% [95%CI = 26%-38%] for infliximab versus 16% [95%CI = 11%-21%] for adalimumab. Infliximab [vs adalimumab; aHR = 1.96; 95%CI = 1.20-3.21] and colonic disease (L2) [vs no L2; aHR = 2.17; 95% CI = 1.26-3.75] were associated with higher discontinuation rates, whereas normalised CRP at three months [aHR = 0.40; 95% CI = 0.19-0.81] with a lower rate. Consistently, patients who switched from adalimumab to infliximab (vs infliximab to adalimumab) had earlier discontinuation (P = 0.04). Concomitant use of immunomodulators was associated with a lower adverse drug reaction-mediated discontinuation rate [aHR = 0.46; 95% CI = 0.28-0.77], in part explained by fewer infusion reactions [aHR = 0.27; 95% CI = 0.08-0.89]. In ulcerative colitis, the probability of discontinuation because of lack/loss of response was 40% [95% CI = 33%-47%] for infliximab versus 37% [95% CI = 21%-53%] for adalimumab. Disease duration >= 10 years [aHR = 0.25; 95% CI = 0.10-0.58] and normalised CRP after three months [aHR = 0.39; 95% CI = 0.18-0.84] were associated with lower discontinuation rates. Conclusions: Clinical characterisation of patients may aid decision-making on anti-TNF treatment. The consistently shorter drug survival for infliximab (vs adalimumab) in Crohns disease, suggests a potential difference between, Funding Agencies: Research committee in Region Örebro County [OLL-685891]; Swedish governments agreement on medical training and research (ALF) [OLL-929900, OLL-549221]

Objectives Clinical trials demonstrated that golimumab is effective in anti-TNF naive patients with ulcerative colitis. We aimed to assess the clinical effectiveness of golimumab in a real-world setting. Materials and methods This was a prospective cohort study, conducted at 16 Swedish hospitals. Data were collected using an electronic case report form. Patients with active ulcerative colitis, defined as Mayo endoscopic subscore >= 2 were eligible for inclusion. The primary outcomes were clinical effectiveness at 12 weeks and 52 weeks, i.e. response (defined as a decrease in Mayo score by >= 3 points or 30% from baseline) and remission (defined as a Mayo score of <= 2 with no individual subscores >1). Results Fifty patients were included. At study entry, 70% were previously exposed to anti-TNF, 16% to vedolizumab, and 96% to immunomodulators. The 12 and 52-week drug continuation rates were 37/50 (74%) and 23/50 (46%), respectively. The 12-week response rate was 14/50 (28%), the remission rate, 8/50 (16%) and the corresponding figures at week 52 were 13/50 (26%) and 10/50 (20%). Among patients who continued golimumab, the median Mayo score decreased from 7 (6-9) at baseline to 1 (0-5) at 52 weeks (p < .01) and the faecal calprotectin decreased from 862 (335-1759) mu g/g to 90 (34-169) mu g/g (p < .01). Clinical response at week 12 was highly predictive of clinical remission at week 52 (adjusted OR: 73.1; 95% CI: 4.5-1188.9). Conclusions The majority of golimumab treated patients represented a treatment refractory patient-group. Despite this, our results confirm that golimumab is an effective therapy in ulcerative colitis., Funding Agencies|MSD; Swedish governments agreement on medical training and research [OLL-836791, OLL-929900]

Background Prospectively and systematically collected real-world data on the effectiveness of ustekinumab (anti-interleukin-12/23) for treating Crohns disease (CD) are still limited. Aim To assess the short-term real-world effectiveness of ustekinumab in Swedish patients with active CD. Methods Prospective multicentre study of adult CD patients initiating ustekinumab according to recommended doses at 20 hospitals, between January 2017 and November 2018. Data were collected through an electronic case report form (eCRF) linked to the Swedish Inflammatory Bowel Disease Registry (SWIBREG). The primary outcomes were clinical response (>= 3-point-decrease of Harvey-Bradshaw index (HBI)) and remission (HBI <= 4 points) at week 16. Secondary outcomes included C-reactive protein (CRP) and haemoglobin (Hb) at baseline compared to week 16. Results Of 114 included patients, 107 (94%) had failed >= 1 and 58 (51%) >= 2 biological agents (anti-tumour necrosis factor [aTNF] agents or vedolizumab). The 16-week ustekinumab retention rate was 105 (92%). Data on HBI at baseline were available for 96 patients. At week 16, response or remission was achieved in 38/96 (40%) patients (25/96 (26%) achieving clinical remission and 23/96 (24%) showing a clinical response). The median CRP concentration (N = 65) decreased from 6 to 4 mg/l (p = .006). No significant changes in Hb were observed. No incident malignancies or infections, requiring antibiotic treatment, were reported. Conclusions In this nation-wide prospective real-world study of adult patients with CD, ustekinumab was associated with clinical effectiveness when administered according to clinical practice and seemed to represent a safe treatment option., Funding Agencies|Janssen Cilag AB, Sweden

Background It is not known to what extent biologic treatment for IBD is captured in the Swedish Prescribed Drug Register (PDR) and the National Patient Register (NPR). Methods A cross-sectional study from July 2005 until 2017, comparing data on biologic treatment in the PDR and the NPR with medical records. We assessed the proportion of started treatment episodes in the medical records that were found in the PDR/NPR ever, within +/- one year and within +/- three months; for any biologic drug, per specific drug (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab), by calendar period (2005-2008, 2009-2012, and 2013-2017) and by study center. For adalimumab, we assessed the validity of end of treatment episodes. Results Medical records of 1361 patients and 2323 treatment episodes with any biologic were reviewed and 80.1% (95% CI: 78.4-81.7) were ever captured in the PDR/NPR in. A time window of +/- one year or +/- three months reduced the sensitivity to 63.3% (95% CI: 61.3-65.3) and 52.6% (95% CI: 50.5-54.6), respectively. The sensitivity was high (>85%) for the prescribed injection drugs adalimumab, golimumab, and ustekinumab for all time windows and for adalimumab end of treatment, while considerably lower for the infusion drugs infliximab and vedolizumab. Conclusions The PDR and the NPR are reliable data sources on treatment with injection biologics in patients with IBD in Sweden. Infliximab and vedolizumab are poorly captured, why PDR/NPR data should only be used after careful consideration of their limitations or complemented by other data sources, e.g., the disease-specific quality register SWIBREG.

Background Prospectively and systematically collected real-world data on the effectiveness of ustekinumab (anti-interleukin-12/23) for treating Crohns disease (CD) are still limited. Aim To assess the short-term real-world effectiveness of ustekinumab in Swedish patients with active CD. Methods Prospective multicentre study of adult CD patients initiating ustekinumab according to recommended doses at 20 hospitals, between January 2017 and November 2018. Data were collected through an electronic case report form (eCRF) linked to the Swedish Inflammatory Bowel Disease Registry (SWIBREG). The primary outcomes were clinical response (>= 3-point-decrease of Harvey-Bradshaw index (HBI)) and remission (HBI <= 4 points) at week 16. Secondary outcomes included C-reactive protein (CRP) and haemoglobin (Hb) at baseline compared to week 16. Results Of 114 included patients, 107 (94%) had failed >= 1 and 58 (51%) >= 2 biological agents (anti-tumour necrosis factor [aTNF] agents or vedolizumab). The 16-week ustekinumab retention rate was 105 (92%). Data on HBI at baseline were available for 96 patients. At week 16, response or remission was achieved in 38/96 (40%) patients (25/96 (26%) achieving clinical remission and 23/96 (24%) showing a clinical response). The median CRP concentration (N = 65) decreased from 6 to 4 mg/l (p = .006). No significant changes in Hb were observed. No incident malignancies or infections, requiring antibiotic treatment, were reported. Conclusions In this nation-wide prospective real-world study of adult patients with CD, ustekinumab was associated with clinical effectiveness when administered according to clinical practice and seemed to represent a safe treatment option., Funding Agencies|Janssen Cilag AB, Sweden

Background: Whether long-term effectiveness differs between anti-tumour necrosis factor (anti-TNF) agents is unknown. Aims: To examine drug survival of first-line anti-TNF agents and identify predictors of discontinuation. To reduce channelling bias, we also compared drug survival of the second anti-TNF. Methods: Biologic-naive patients (N = 955) recorded in the Swedish IBD Quality Register (SWIBREG) were examined. We used propensity score matching, comparing drug survival over up to three years of follow-up. Cox regression estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Results: In Crohns disease, discontinuation because of lack/loss of response was 32% [95%CI = 26%-38%] for infliximab versus 16% [95%CI = 11%-21%] for adalimumab. Infliximab [vs adalimumab; aHR = 1.96; 95%CI = 1.20-3.21] and colonic disease (L2) [vs no L2; aHR = 2.17; 95% CI = 1.26-3.75] were associated with higher discontinuation rates, whereas normalised CRP at three months [aHR = 0.40; 95% CI = 0.19-0.81] with a lower rate. Consistently, patients who switched from adalimumab to infliximab (vs infliximab to adalimumab) had earlier discontinuation (P = 0.04). Concomitant use of immunomodulators was associated with a lower adverse drug reaction-mediated discontinuation rate [aHR = 0.46; 95% CI = 0.28-0.77], in part explained by fewer infusion reactions [aHR = 0.27; 95% CI = 0.08-0.89]. In ulcerative colitis, the probability of discontinuation because of lack/loss of response was 40% [95% CI = 33%-47%] for infliximab versus 37% [95% CI = 21%-53%] for adalimumab. Disease duration >= 10 years [aHR = 0.25; 95% CI = 0.10-0.58] and normalised CRP after three months [aHR = 0.39; 95% CI = 0.18-0.84] were associated with lower discontinuation rates. Conclusions: Clinical characterisation of patients may aid decision-making on anti-TNF treatment. The consistently shorter drug survival for infliximab (vs adalimumab) in Crohns disease, suggests a potential difference between, Funding Agencies: Research committee in Region Örebro County [OLL-685891]; Swedish governments agreement on medical training and research (ALF) [OLL-929900, OLL-549221]

Objectives Clinical trials demonstrated that golimumab is effective in anti-TNF naive patients with ulcerative colitis. We aimed to assess the clinical effectiveness of golimumab in a real-world setting. Materials and methods This was a prospective cohort study, conducted at 16 Swedish hospitals. Data were collected using an electronic case report form. Patients with active ulcerative colitis, defined as Mayo endoscopic subscore >= 2 were eligible for inclusion. The primary outcomes were clinical effectiveness at 12 weeks and 52 weeks, i.e. response (defined as a decrease in Mayo score by >= 3 points or 30% from baseline) and remission (defined as a Mayo score of <= 2 with no individual subscores >1). Results Fifty patients were included. At study entry, 70% were previously exposed to anti-TNF, 16% to vedolizumab, and 96% to immunomodulators. The 12 and 52-week drug continuation rates were 37/50 (74%) and 23/50 (46%), respectively. The 12-week response rate was 14/50 (28%), the remission rate, 8/50 (16%) and the corresponding figures at week 52 were 13/50 (26%) and 10/50 (20%). Among patients who continued golimumab, the median Mayo score decreased from 7 (6-9) at baseline to 1 (0-5) at 52 weeks (p < .01) and the faecal calprotectin decreased from 862 (335-1759) mu g/g to 90 (34-169) mu g/g (p < .01). Clinical response at week 12 was highly predictive of clinical remission at week 52 (adjusted OR: 73.1; 95% CI: 4.5-1188.9). Conclusions The majority of golimumab treated patients represented a treatment refractory patient-group. Despite this, our results confirm that golimumab is an effective therapy in ulcerative colitis., Funding Agencies|MSD; Swedish governments agreement on medical training and research [OLL-836791, OLL-929900]

BACKGROUND: To avoid a permanent stoma, restorative surgery is performed after the colectomy. Previous studies have shown that less than half of patients with ulcerative colitis undergo restorative surgery. OBJECTIVE: The primary aim was to explore the association between socioeconomic status and restorative surgery after colectomy. DESIGN: This was a nationwide register-based cohort study. SETTINGS: The study was conducted in Sweden. PATIENTS: All Swedish patients with ulcerative colitis who underwent colectomy between 1990 and 2017 at the age of 15 to 69 years were included. MAIN OUTCOME MEASURES: The main outcome was restorative surgery, and the secondary outcome was failure of the reconstruction (defined as the need for a new ileostomy after the reconstruction or nonreversal of a defunctioning stoma within 2 years of the reconstruction). To calculate HRs for restorative surgery after colectomy, as well as failure after restorative surgery, multivariable Cox regression models were performed (adjusted for sex, year of colectomy, colorectal cancer diagnosis, education, civil status, country of birth, income (quartiles 1 to 4, where Q4 represents highest income), hospital volume, and stratified by age). RESULTS: In all, 5969 patients with ulcerative colitis underwent colectomy, and of those, 2794 (46.8%) underwent restorative surgery. Restorative surgery was more common in patients with a high income at the time of colectomy (quartile 1, reference; quartile 2, 1.09 (0.98-1.21); quartile 3, 1.20 (1.07-1.34); quartile 4, 1.27 (1.13-1.43)) and less common in those born in a Nordic country than in immigrants born in a non-Nordic country (0.86 (0.74-0.99)), whereas no association was seen with educational level and civil status. There was no association between socioeconomic status and the risk of failure after restorative surgery. LIMITATIONS: The study was restricted to register data. CONCLUSIONS: Restorative surgery in ulcerative colitis appears to be more common in p, Funding Agencies|Region Stockholm; Bengt Ihre research fellowship; Karolinska Institutet foundationKarolinska Institutet; Karolinska Institutets Young Scholar Award from the Strategic Research Area Epidemiology Program; Swedish Medical Society; Bengt Ihre foundation

Objectives Clinical trials demonstrated that golimumab is effective in anti-TNF naive patients with ulcerative colitis. We aimed to assess the clinical effectiveness of golimumab in a real-world setting. Materials and methods This was a prospective cohort study, conducted at 16 Swedish hospitals. Data were collected using an electronic case report form. Patients with active ulcerative colitis, defined as Mayo endoscopic subscore >= 2 were eligible for inclusion. The primary outcomes were clinical effectiveness at 12 weeks and 52 weeks, i.e. response (defined as a decrease in Mayo score by >= 3 points or 30% from baseline) and remission (defined as a Mayo score of <= 2 with no individual subscores >1). Results Fifty patients were included. At study entry, 70% were previously exposed to anti-TNF, 16% to vedolizumab, and 96% to immunomodulators. The 12 and 52-week drug continuation rates were 37/50 (74%) and 23/50 (46%), respectively. The 12-week response rate was 14/50 (28%), the remission rate, 8/50 (16%) and the corresponding figures at week 52 were 13/50 (26%) and 10/50 (20%). Among patients who continued golimumab, the median Mayo score decreased from 7 (6-9) at baseline to 1 (0-5) at 52 weeks (p < .01) and the faecal calprotectin decreased from 862 (335-1759) mu g/g to 90 (34-169) mu g/g (p < .01). Clinical response at week 12 was highly predictive of clinical remission at week 52 (adjusted OR: 73.1; 95% CI: 4.5-1188.9). Conclusions The majority of golimumab treated patients represented a treatment refractory patient-group. Despite this, our results confirm that golimumab is an effective therapy in ulcerative colitis., Funding Agencies|MSD; Swedish governments agreement on medical training and research [OLL-836791, OLL-929900]

Background: Whether long-term effectiveness differs between anti-tumour necrosis factor (anti-TNF) agents is unknown. Aims: To examine drug survival of first-line anti-TNF agents and identify predictors of discontinuation. To reduce channelling bias, we also compared drug survival of the second anti-TNF. Methods: Biologic-naive patients (N = 955) recorded in the Swedish IBD Quality Register (SWIBREG) were examined. We used propensity score matching, comparing drug survival over up to three years of follow-up. Cox regression estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Results: In Crohns disease, discontinuation because of lack/loss of response was 32% [95%CI = 26%-38%] for infliximab versus 16% [95%CI = 11%-21%] for adalimumab. Infliximab [vs adalimumab; aHR = 1.96; 95%CI = 1.20-3.21] and colonic disease (L2) [vs no L2; aHR = 2.17; 95% CI = 1.26-3.75] were associated with higher discontinuation rates, whereas normalised CRP at three months [aHR = 0.40; 95% CI = 0.19-0.81] with a lower rate. Consistently, patients who switched from adalimumab to infliximab (vs infliximab to adalimumab) had earlier discontinuation (P = 0.04). Concomitant use of immunomodulators was associated with a lower adverse drug reaction-mediated discontinuation rate [aHR = 0.46; 95% CI = 0.28-0.77], in part explained by fewer infusion reactions [aHR = 0.27; 95% CI = 0.08-0.89]. In ulcerative colitis, the probability of discontinuation because of lack/loss of response was 40% [95% CI = 33%-47%] for infliximab versus 37% [95% CI = 21%-53%] for adalimumab. Disease duration >= 10 years [aHR = 0.25; 95% CI = 0.10-0.58] and normalised CRP after three months [aHR = 0.39; 95% CI = 0.18-0.84] were associated with lower discontinuation rates. Conclusions: Clinical characterisation of patients may aid decision-making on anti-TNF treatment. The consistently shorter drug survival for infliximab (vs adalimumab) in Crohns disease, suggests a potential difference between, Funding Agencies: Research committee in Region Örebro County [OLL-685891]; Swedish governments agreement on medical training and research (ALF) [OLL-929900, OLL-549221]

Background Prospectively and systematically collected real-world data on the effectiveness of ustekinumab (anti-interleukin-12/23) for treating Crohns disease (CD) are still limited. Aim To assess the short-term real-world effectiveness of ustekinumab in Swedish patients with active CD. Methods Prospective multicentre study of adult CD patients initiating ustekinumab according to recommended doses at 20 hospitals, between January 2017 and November 2018. Data were collected through an electronic case report form (eCRF) linked to the Swedish Inflammatory Bowel Disease Registry (SWIBREG). The primary outcomes were clinical response (>= 3-point-decrease of Harvey-Bradshaw index (HBI)) and remission (HBI <= 4 points) at week 16. Secondary outcomes included C-reactive protein (CRP) and haemoglobin (Hb) at baseline compared to week 16. Results Of 114 included patients, 107 (94%) had failed >= 1 and 58 (51%) >= 2 biological agents (anti-tumour necrosis factor [aTNF] agents or vedolizumab). The 16-week ustekinumab retention rate was 105 (92%). Data on HBI at baseline were available for 96 patients. At week 16, response or remission was achieved in 38/96 (40%) patients (25/96 (26%) achieving clinical remission and 23/96 (24%) showing a clinical response). The median CRP concentration (N = 65) decreased from 6 to 4 mg/l (p = .006). No significant changes in Hb were observed. No incident malignancies or infections, requiring antibiotic treatment, were reported. Conclusions In this nation-wide prospective real-world study of adult patients with CD, ustekinumab was associated with clinical effectiveness when administered according to clinical practice and seemed to represent a safe treatment option., Funding Agencies|Janssen Cilag AB, Sweden

Background It is not known to what extent biologic treatment for IBD is captured in the Swedish Prescribed Drug Register (PDR) and the National Patient Register (NPR). Methods A cross-sectional study from July 2005 until 2017, comparing data on biologic treatment in the PDR and the NPR with medical records. We assessed the proportion of started treatment episodes in the medical records that were found in the PDR/NPR ever, within +/- one year and within +/- three months; for any biologic drug, per specific drug (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab), by calendar period (2005-2008, 2009-2012, and 2013-2017) and by study center. For adalimumab, we assessed the validity of end of treatment episodes. Results Medical records of 1361 patients and 2323 treatment episodes with any biologic were reviewed and 80.1% (95% CI: 78.4-81.7) were ever captured in the PDR/NPR in. A time window of +/- one year or +/- three months reduced the sensitivity to 63.3% (95% CI: 61.3-65.3) and 52.6% (95% CI: 50.5-54.6), respectively. The sensitivity was high (>85%) for the prescribed injection drugs adalimumab, golimumab, and ustekinumab for all time windows and for adalimumab end of treatment, while considerably lower for the infusion drugs infliximab and vedolizumab. Conclusions The PDR and the NPR are reliable data sources on treatment with injection biologics in patients with IBD in Sweden. Infliximab and vedolizumab are poorly captured, why PDR/NPR data should only be used after careful consideration of their limitations or complemented by other data sources, e.g., the disease-specific quality register SWIBREG.

Background It is not known to what extent biologic treatment for IBD is captured in the Swedish Prescribed Drug Register (PDR) and the National Patient Register (NPR). Methods A cross-sectional study from July 2005 until 2017, comparing data on biologic treatment in the PDR and the NPR with medical records. We assessed the proportion of started treatment episodes in the medical records that were found in the PDR/NPR ever, within +/- one year and within +/- three months; for any biologic drug, per specific drug (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab), by calendar period (2005-2008, 2009-2012, and 2013-2017) and by study center. For adalimumab, we assessed the validity of end of treatment episodes. Results Medical records of 1361 patients and 2323 treatment episodes with any biologic were reviewed and 80.1% (95% CI: 78.4-81.7) were ever captured in the PDR/NPR in. A time window of +/- one year or +/- three months reduced the sensitivity to 63.3% (95% CI: 61.3-65.3) and 52.6% (95% CI: 50.5-54.6), respectively. The sensitivity was high (>85%) for the prescribed injection drugs adalimumab, golimumab, and ustekinumab for all time windows and for adalimumab end of treatment, while considerably lower for the infusion drugs infliximab and vedolizumab. Conclusions The PDR and the NPR are reliable data sources on treatment with injection biologics in patients with IBD in Sweden. Infliximab and vedolizumab are poorly captured, why PDR/NPR data should only be used after careful consideration of their limitations or complemented by other data sources, e.g., the disease-specific quality register SWIBREG.

Introduction: Whether data on International Classification of Diseases (ICD)-codes from the Swedish National Patient Register (NPR) correctly correspond to subtypes of inflammatory bowel disease (IBD) and phenotypes of the Montreal classification scheme among patients with prevalent disease is unknown. Materials and methods: We obtained information on IBD subtypes and phenotypes from the medical records of 1403 patients with known IBD who underwent biological treatment at ten Swedish hospitals and retrieved information on their IBD-associated diagnostic codes from the NPR. We used previously described algorithms to define IBD subtypes and phenotypes. Finally, we compared these register-generated subtypes and phenotypes with the corresponding information from the medical records and calculated positive predictive values (PPV) with 95% confidence intervals. Results: Among patients with clinically confirmed disease and diagnostic listings of IBD in the NPR (N = 1401), the PPV was 97 (96-99)% for Crohns disease, 98 (97-100)% for ulcerative colitis, and 8 (4-11)% for IBD-unclassified. The overall accuracy for age at diagnosis was 95% (when defined as A1, A2, or A3). Examining the validity of codes representing disease phenotype, the PPV was 36 (32-40)% for colonic Crohns disease (L2), 61 (56-65)% for non-stricturing/non-penetrating Crohns disease behaviour (B1) and 83 (78-87)% for perianal disease. Correspondingly, the PPV was 80 (71-89)% for proctitis (E1)/left-sided colitis (E2) in ulcerative colitis. Conclusions: Among people with known IBD, the NPR is a reliable source of data to classify most subtypes of prevalent IBD, even though misclassification commonly occurred in Crohns disease location and behaviour and also among IBD-unclassified patients.