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BACKGROUND AND AIMS: Individuals with inflammatory bowel disease (IBD) are at increased risk of serious infections, but whether this risk varies by histological disease activity is unclear. METHODS: A national population-based study of 55,626 individuals diagnosed with IBD in 1990-2016 with longitudinal data on ileo-colorectal biopsies followed through 2016. Serious infections were defined as having an inpatient infectious disease diagnosis in the Swedish National Patient Register. We used Cox regression to estimate hazard ratios (HRs) for serious infections in the 12 months following documentation of histologic inflammation (vs. histological remission), adjusting for social and demographic factors, chronic comorbidities, prior IBD-related surgery and hospitalization. We also adjusted for IBD-related medications in sensitivity analyses. RESULTS: With histological inflammation vs. remission, there was 4.62 (95%CI=4.46-4.78) and 2.53 (95%CI=2.36-2.70) serious infections per 100 person-years of follow-up, respectively (adjusted [a]HR=1.59; 95%CI=1.48-1.72). Histological inflammation (vs. remission) were associated with an increased risk of serious infections in ulcerative colitis (UC, aHR=1.68; 95%CI=1.51-1.87) and Crohn's disease (CD, aHR=1.59; 95%CI=1.40-1.80). The aHRs of sepsis and opportunistic infections were 1.66 (95%CI=1.28-2.15) and 1.71 (95%CI=1.22-2.41), respectively. Overall, results were consistent across age groups, sex and education level and remained largely unchanged after adjustment for IBD-related medications (aHR=1.47; 95%CI=1.34-1.61). CONCLUSION: Histological inflammation of IBD was an independent risk factor of serious infections, including sepsis, suggesting that achieving histological remission may reduce infections in IBD., Funding Agencies:ALF-funding from Region Västra GötalandUniversity of Gothenburg, SwedenBirgitta och Göran Karlssons foundationThe Swedish Society for Medical ResearchThe Swedish Research CouncilThe Swedish Society of MedicineKarolinska InstitutetSwedish Research CouncilThe Swedish Society of MedicineRegion Stockholm (ALF project)Crohn’s and Colitis FoundationJudith Stewart Colton Center for AutoimmunityNIH NIDDK Diseases

Background Real-world data on starting intravenous (IV) vedolizumab (VDZ) and transitioning to subcutaneous (SC) treatment in inflammatory bowel disease (IBD) are scarce. Aims To assess treatment outcomes of patients with IBD starting IV VDZ and switching to SC VDZ in routine clinical care. Methods Adult patients with IBD switching from IV to SC VDZ treatment between 1 March 2020 and 31 December 2021 were identified from the Swedish IBD quality register. The primary outcome was SC VDZ persistence. Secondary outcomes included clinical remission, changes in quality of life (QoL) according to EuroQual 5-Dimensions 5-Levels (EQ-5D-5L) and the Short-Health Scale (SHS) and inflammatory markers, including faecal Calprotectin (FCP). Results Altogether, 406 patients with IBD (Crohn's disease, n = 181; ulcerative colitis, n = 225) were identified. After a median follow-up of 30 months from starting IV VDZ treatment, the persistence rates were 98%(178/181) in Crohn's disease and 94% (211/225) in ulcerative colitis. Most patients (84%) transitioned during maintenance therapy, and the median follow-up from switch to SC VDZ was 10 months. Compared to baseline, statistically significant improvements were observed in all domains of the SHS, EQ-5D index value and visual analogue scale. Median (interquartile range) FCP concentrations (mu g/g) decreased from 459 (185-1001) to 65 (26-227) in Crohn's disease (n = 45; p < 0.001) and from 646 (152-1450) to 49 (20-275) in ulcerative colitis (n = 58; p < 0.001). Conclusion Initiating IV VDZ and switching to SC treatment was associated with high persistence rates and improvements in measures of QoL and FCP. These findings are reassuring for patients who start IV VDZ and switch to SC VDZ., Funding Agencies|Orebro University [OLL-836791]; Takeda Pharma AB [VedolizumabSC-4002]; Region Orebro County [OLL-836791]

BACKGROUND: Serious infections have been observed in patients with inflammatory bowel disease (IBD) on anti-TNF use-but to what extent these infections are due to anti-TNF or the disease activity per se is hard to disentangle. We aimed to describe how the rates of serious infections change over time both before and after starting anti-TNF in IBD. METHODS: Inflammatory bowel disease patients naïve to anti-TNF treatment were identified at 5 centers participating in the Swedish IBD Quality Register, and their medical records examined in detail. Serious infections, defined as infections requiring in-patient care, the year before and after the start of anti-TNF treatment were evaluated. RESULTS: Among 980 patients who started their first anti-TNF therapy between 1999 and 2016, the incidence rate of serious infections was 2.19 (95% CI,1.43-3.36) per 100 person years the year before and 2.11 (95% CI, 1.33-3.34) per 100 person years 1 year after treatment start. This corresponded to an incidence rate ratio 1 year after anti-TNF treatment of 0.97 (95% CI, 0.51-1.84). Compared with before anti-TNF therapy, the incidence of serious infection was significantly decreased more than 1 year after treatment (incidence rate ratio 0.56; 95% CI, 0.33-0.95; P = .03). CONCLUSIONS: In routine clinical practice in Sweden, the incidence rate of serious infection among IBD patients did not increase with anti-TNF therapy. Instead, serious infections seemed to decrease more than 1 year after initiation of anti-TNF treatment.

Background and aims Therapeutic drug monitoring (TDM) may optimize biologic and thiopurine therapies in inflammatory bowel disease (IBD). The study aimed to investigate implementation and utilization of TDM in Scandinavia. Methods A web-based questionnaire on the use of TDM was distributed to Scandinavian gastroenterologists via the national societies. Results In total, 297 IBD physicians prescribing biologic therapies, equally distributed between community and university hospitals, were included (response rate 42%) (Norway 118 (40%), Denmark 86 (29%), Sweden 50 (17%), Finland 33 (11%), Iceland 10 (3%)). Overall, TDM was applied during biologic therapies by 87%, and for TNF-inhibitors >90%. Among the users, reactive and proactive TDM were utilized by 90% and 63%, respectively. Danish physicians were significantly less inclined to use TDM compared to other Scandinavian countries; (58% vs 98%); OR 0.03 [0.01-0.09], p < 0.001). Reactive TDM was commonly applied at primary (74%) and secondary (99%) treatment failure. Proactive TDM was used by 80% during maintenance therapy and 56% during induction and more commonly utilized in Norway (p < 0.001), and by physicians managing >10 IBD patients/week (p = 0.005). TDM scenarios were interpreted in accord with available evidence but with discrepancies for proactive TDM. The main barriers to TDM were lack of guidelines (51%) and time lag between sampling and results (49%). TDM of thiopurines was routinely used by 87%. Conclusion TDM of biologic and thiopurine therapies has been broadly implemented into clinical practice in Scandinavia. However, physicians call for TDM guidelines detailing indications and interpretations of test results along with improved test response times., Funding Agencies|Akershus University Hospital

Background Health-related quality of life (hrQoL) may be the most important patient-reported outcome for patients with chronic disorders. The Short Health Scale (SHS) is a brief four-item instrument to assess hrQoL in patients with bowel disorders. This study examined the validity, reliability and sensitivity of the German translation of the SHS in a cohort of outpatients with inflammatory bowel diseases (IBD).Methods The study was preregistered in April 2021 ( https://doi.org/10.17605/OSF.IO/S82D9 ). Outpatients with IBD (n=225) in different stages of disease activity (as determined by the Harvey-Bradshaw index or partial Mayo score) completed the German SHS and the short Inflammatory Bowel Disease Questionnaire (sIBDQ) as an established measure of hrQoL to examine the convergent validity. To assess reliability, a subset of patients (n=30) in remission completed the same questionnaires after 4-8 weeks. Sensitivity to change was established from questionnaires of patients with either decreased (n=15) or increased (n=16) disease activity after 3-6 months.Results The internal consistency of the German SHS was high (Cronbachs a=0.860). SHS total scores correlated strongly with sIBDQ scores (?=-0.760, p<0.001) and disease activity (?=0.590, p<0.001). Retest reliability was high (?=0.695, p<0.001). Sensitivity to change was statistically significant for patients with decreased (p=0.013) but not increased (p=0.134) disease activity.Conclusion The German version of the SHS is a valid and reliable tool to measure hrQoL in persons with IBD., Funding Agencies|Land Baden-Wurttemberg (BW-ZDFP) | Deutsche Forschungsgemeinschaft [GRK 2350, GRK2727, RE 2706, TH2341]

Aims: To investigate the diagnostic accuracy of fecal calprotectin (FC) for inflammatory bowel disease (IBD) and organic gastrointestinal disease (OGID) in primary care. To examine the association with demographic factors, symptoms and concomitant medical therapy.Methods: A retrospective analysis of data on all semiquantitative FC tests from individuals =18 years conducted in primary care in ostergotland County in 2010. A 5-year follow-up with inclusion of new gastrointestinal diagnoses.Results: A total of 1293 eligible patients were included. IBD was found in 8.8% and other OGID in 30.8% of patients with positive FC. Positive FC was associated with diarrhea, age >60 years, duration <3 months, use of nonsteroidal anti-inflammatory drug (NSAID), and proton pump inhibitor (PPI). Predictors of IBD were positive FC, diarrhea, rectal bleeding, and male sex; predictors of OGID positive FC, age >35 years, abnormal clinical findings, and duration <3 months. FC yielded the highest sensitivity and negative predictive value compared with demographic factors, symptoms, and duration. Use of NSAID and PPI showed a marginal increase in the sensitivity, positive predictive value, and decrease in the specificity of FC. Within 5 years, 4.0% had a new gastrointestinal diagnosis among patients with positive FC (0.6% IBD).Conclusions: FC reliably rules out IBD and contradicts the presence of other OGID in primary care patients. Positive FC test together with other predictors, such as diarrhea, rectal bleeding, short duration, or age >35 years, should encourage a prioritized investigation. Use of NSAID, PPI, and ASA may affect the diagnostic accuracy of FC for IBD and OGID., Funding Agencies|County Council of Ostergotland, Sweden

Background:Real-world data on long-term outcomes of vedolizumab (VDZ) are scarce. Objective:To assess long-term outcomes (up to 3 years) of VDZ in treating inflammatory bowel disease (IBD). Design:A nationwide, prospective multicentre extension of a Swedish observational study on VDZ assessing Effectiveness And Healthcare resource utilization in patients with IBD (SVEAH). Methods:After re-consent, data of patients with Crohns disease (CD) (n = 68) and ulcerative colitis (UC) (n = 46) treated with VDZ were prospectively recorded using an electronic case report form integrated with the Swedish IBD Register (SWIBREG). The primary outcome was clinical remission (defined as Harvey-Bradshaw Index <= 4 in CD and partial Mayo score <= 2 in UC) at 104 and 156 weeks in patients with a response and/or remission 12 weeks after starting VDZ. Secondary outcomes included health-related quality of life (HRQoL) and biochemical outcomes. Results:VDZ continuation rates were high at weeks 104 and 156, 88% and 84%, respectively, for CD and 87% and 78%, respectively, for UC. Of the 53 CD patients with a response/remission at 12 weeks, 40 (75%) patients were in remission at 104 weeks and 42 (79%) patients at 156 weeks. For UC, these numbers were 25/31 (81%) and 22/31 (71%), respectively. Improvements were seen in the Short Health Scale (p < 0.01 for each dimension; CD, n = 51; UC, n = 33) and the EuroQol 5-Dimensions, 5-levels index value (p < 0.01; CD, n = 39; UC, n = 30). Median plasma-C-reactive protein concentrations (mg/L) decreased from 5 at baseline to 4 in CD (p = 0.01, n = 53) and from 5 to 4 in UC (p = 0.03, n = 34) at 156 weeks. Correspondingly, median faecal-calprotectin (mu g/g) decreased from 641 to 114 in CD patients (p < 0.01, n = 26) and from 387 to 37 in UC patients (p = 0.02, n = 17). Conclusion:VDZ demonstrated high continuation rates and was associated with improvements in clinical outcomes, HRQoL measures and inflammatory markers at, Funding Agencies|Takeda [EUPAS22735]; Swedish governments agreement on medical training and research [OLL-836791, OLL-934569, OLL-929900, OLL-960775]

Introduction: Fecal calprotectin (FC) is anoninvasive tool for examining response to biologics in inflammatory boweldisease (IBD), but its performance in relation to other novel fecal markers of various cellular origins is unknown. Methods: We performed a prospective multicenter cohort study and included patients with active IBD who provided a fecal sample at initiation of biological therapy. Levels of FC, myeloperoxidase (MPO), human neutrophil lipocalin (HNL), and eosinophil-derived neurotoxin (EDN) were analyzed and related to clinical remission status at 3 months. Changes in levels of markers at 3 months were calculated, and the impact of concomitant use of corticosteroids at baseline was estimated. Results: In patients achieving clinical remission (n = 27), a decrease in levels of FC (P = 0.005), MPO (P < 0.001), HNL (P < 0.001), and EDN (P < 0.001) was observed, whereas no significant decrease was seen in patients not achieving remission (n = 39). There was a significant difference in the change in the level of MPO (P = 0.01) and HNL (P = 0.02) between patients achieving clinical remission and those who did not, but changes in FC and EDN could not differentiate between these groups. Patients with concomitant systemic corticosteroids at inclusion had lower levels of HNL (P = 0.01) and EDN (P < 0.001) at baseline, compared with patients without corticosteroids. Discussion: Fecal MPO, HNL, and EDN are all promising biomarkers for assessing the treatment outcome of biologics in patients with IBD. Fecal levels of EDN and HNL are significantly affected by corticosteroids indicating a greater sensitivity to the effects of corticosteroids compared with levels of FC and MPO., This work was supported by the Swedish Foundation for Strategic Research (grant number RB13-016), Medical Faculty, Uppsala University, Uppsala, Sweden (M.C.) and the Orebro University Hospital Research Foundation (grant numbers OLL-936004, OLL-890291, OLL-790011, OLL-723021, and OLL-333321 to J.H.).

Background and aims: Therapeutic drug monitoring (TDM) may optimize biologic and thiopurine therapies in inflammatory bowel disease (IBD). The study aimed to investigate implementation and utilization of TDM in Scandinavia. Methods: A web-based questionnaire on the use of TDM was distributed to Scandinavian gastroenterologists via the national societies. Results: In total, 297 IBD physicians prescribing biologic therapies, equally distributed between community and university hospitals, were included (response rate 42%) (Norway 118 (40%), Denmark 86 (29%), Sweden 50 (17%), Finland 33 (11%), Iceland 10 (3%)). Overall, TDM was applied during biologic therapies by 87%, and for TNF-inhibitors >90%. Among the users, reactive and proactive TDM were utilized by 90% and 63%, respectively. Danish physicians were significantly less inclined to use TDM compared to other Scandinavian countries; (58% vs 98%); OR 0.03 [0.01–0.09], p < 0.001). Reactive TDM was commonly applied at primary (74%) and secondary (99%) treatment failure. Proactive TDM was used by 80% during maintenance therapy and 56% during induction and more commonly utilized in Norway (p < 0.001), and by physicians managing >10 IBD patients/week (p = 0.005). TDM scenarios were interpreted in accord with available evidence but with discrepancies for proactive TDM. The main barriers to TDM were lack of guidelines (51%) and time lag between sampling and results (49%). TDM of thiopurines was routinely used by 87%. Conclusion: TDM of biologic and thiopurine therapies has been broadly implemented into clinical practice in Scandinavia. However, physicians call for TDM guidelines detailing indications and interpretations of test results along with improved test response times.

Introduction: Fecal calprotectin (FC) is a noninvasive tool for examining response to biologics in inflammatory bowel disease (IBD), but its performance in relation to other novel fecal markers of various cellular origins is unknown. Methods: We performed a prospective multicenter cohort study and included patients with active IBD who provided a fecal sample at initiation of biological therapy. Levels of FC, myeloperoxidase (MPO), human neutrophil lipocalin (HNL), and eosinophil-derived neurotoxin (EDN) were analyzed and related to clinical remission status at 3 months. Changes in levels of markers at 3 months were calculated, and the impact of concomitant use of corticosteroids at baseline was estimated. Results: In patients achieving clinical remission (n = 27), a decrease in levels of FC ( P = 0.005), MPO ( P < 0.001), HNL ( P < 0.001), and EDN ( P < 0.001) was observed, whereas no significant decrease was seen in patients not achieving remission (n = 39). There was a significant difference in the change in the level of MPO ( P = 0.01) and HNL ( P = 0.02) between patients achieving clinical remission and those who did not, but changes in FC and EDN could not differentiate between these groups. Patients with concomitant systemic corticosteroids at inclusion had lower levels of HNL ( P = 0.01) and EDN ( P < 0.001) at baseline, compared with patients without corticosteroids. Discussion: Fecal MPO, HNL, and EDN are all promising biomarkers for assessing the treatment outcome of biologics in patients with IBD. Fecal levels of EDN and HNL are significantly affected by corticosteroids indicating a greater sensitivity to the effects of corticosteroids compared with levels of FC and MPO., Funding: Swedish Foundation for Strategic Research [RB13-016]; Medical Faculty, Uppsala University, Uppsala, Sweden; Orebro University Hospital Research Foundation [OLL-936004, OLL-890291, OLL-790011, OLL-723021, OLL-333321]

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the gastrointestinal tract, which generally manifests as Crohn's disease (CD) or ulcerative colitis (UC). These subtypes are heterogeneous in terms of disease location and histological features, while sharing common clinical presentation, genetic associations and thus, common immune regulatory pathways. METHODS: Using miRNA and mRNA coupled transcriptome profiling and systems biology approaches, we report a comprehensive analysis of blood transcriptomes from treatment-naïve (n=110) and treatment-exposed (n=177) IBD patients as well as symptomatic- (n=65) and healthy controls (n=95). RESULTS: Broadly, the peripheral blood transcriptomes of CD and UC patients were similar. However, there was an extensive gene deregulation in the blood of IBD patients, while only a slight deregulation in symptomatic controls, when compared with healthy controls. The deregulated mRNAs and miRNAs are mainly involved in the innate immunity and are especially enriched in neutrophil activation-related pathways. Oxidative phosphorylation and neutrophil activation-related modules were found to be differentially co-expressed among treatment-naïve IBD as compared to healthy controls. In the deregulated neutrophil activation-related co-expression module, the IL1B was identified as the central gene. The co-expression levels among IL1B and chemosensing receptor (CXCR1/2 and FPR1/2) genes were reduced in the blood of IBD patients when compared with healthy controls. CONCLUSIONS: Immune dysregulation seen in peripheral blood transcriptomes of treatment-naïve IBD patients is mainly driven by neutrophil activation., Funding agency:German Research Foundation (DFG) EXC 2167

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 Crohn's 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.

Background and aims Therapeutic drug monitoring (TDM) may optimize biologic and thiopurine therapies in inflammatory bowel disease (IBD). The study aimed to investigate implementation and utilization of TDM in Scandinavia. Methods A web-based questionnaire on the use of TDM was distributed to Scandinavian gastroenterologists via the national societies. Results In total, 297 IBD physicians prescribing biologic therapies, equally distributed between community and university hospitals, were included (response rate 42%) (Norway 118 (40%), Denmark 86 (29%), Sweden 50 (17%), Finland 33 (11%), Iceland 10 (3%)). Overall, TDM was applied during biologic therapies by 87%, and for TNF-inhibitors >90%. Among the users, reactive and proactive TDM were utilized by 90% and 63%, respectively. Danish physicians were significantly less inclined to use TDM compared to other Scandinavian countries; (58% vs 98%); OR 0.03 [0.01-0.09], p < 0.001). Reactive TDM was commonly applied at primary (74%) and secondary (99%) treatment failure. Proactive TDM was used by 80% during maintenance therapy and 56% during induction and more commonly utilized in Norway (p < 0.001), and by physicians managing >10 IBD patients/week (p = 0.005). TDM scenarios were interpreted in accord with available evidence but with discrepancies for proactive TDM. The main barriers to TDM were lack of guidelines (51%) and time lag between sampling and results (49%). TDM of thiopurines was routinely used by 87%. Conclusion TDM of biologic and thiopurine therapies has been broadly implemented into clinical practice in Scandinavia. However, physicians call for TDM guidelines detailing indications and interpretations of test results along with improved test response times., Funding Agencies|Akershus University Hospital

Background Real-world data on clinical outcomes of ustekinumab in ulcerative colitis are lacking. Objective To assess short- and long-term clinical outcomes of ustekinumab in ulcerative colitis. Methods Adult ulcerative colitis patients without previous colectomy starting ustekinumab treatment up until 11 December 2020 were identified through the Swedish Inflammatory Bowel Disease Register (SWIBREG). Prospectively recorded data were extracted from the SWIBREG. The primary outcome was persistence to ustekinumab 16 weeks after treatment initiation. Secondary outcomes included drug persistence beyond week 16, clinical remission (defined as a patient-reported Mayo rectal bleeding subscore = 0 and stool frequency subscore <= 1), biochemical remission (defined as faecal-calprotectin <250 mu g/g) and changes in health-related quality of life (HRQoL), as measured by the Short Health Scale (SHS). Logistic regression was used to identify potential predictors of ustekinumab persistence at 16 weeks. Results Of the 133 patients with ulcerative colitis, only three were naive to biologics and tofacitinib. The persistence rates of ustekinumab were 115/133 (86%) at 16 weeks and 89/133 (67%) at last follow-up, that is, after a median follow-up of 32 (interquartile range 19-56) weeks. The clinical remission rates were 17% at 16 weeks and 32% at the last follow-up. The corresponding rates for biochemical remission were 14% and 23%. The median faecal-calprotectin concentration decreased from 740 mu g/g at baseline to 98 mu g/g at the last follow-up (p < 0.01, n = 37). Improvement was seen in each dimension of the SHS between baseline and last follow-up (p < 0.01 for each dimension, n = 46). Male sex was associated with ustekinumab persistence at 16 weeks (adjusted odds ratio = 4.00, 95% confidence interval: 1.35-11.83). Conclusion In this nationwide real-world cohort of ulcerative colitis patients with prior drug failures, including other biologics and tofaci, Funding Agencies|Janssen Pharmaceuticals [CNTO1275UCO0001]

IntroductionCollagenous colitis (CC) is an inflammatory bowel disease, which usually responds to budesonide treatment. Our aim was to study the immunological background of the disease. MethodsAnalyses of peripheral and mucosal MAIT (mucosa associated invariant T cells) and NK (natural killer) cells were performed with flow cytometry. Numbers of mucosal cells were calculated using immunohistochemistry. We studied the same patients with active untreated CC (au-CC) and again while in remission on budesonide treatment. Budesonide refractory patients and healthy controls were also included. The memory marker CD45R0 and activation marker CD154 and CD69 were used to further study the cells. Finally B cells, CD4(+) and CD8(+) T cells were also analysed. ResultsThe percentages of circulating CD56(dim)CD16(+) NK cells as well as MAIT cells (CD3(+)TCRVa7.2(+)CD161(+)) were decreased in au-CC compared to healthy controls. This difference was not seen in the mucosa; where we instead found increased numbers of mucosal CD4(+) T cells and CD8(+) T cells in au-CC. Mucosal immune cell numbers were not affected by budesonide treatment. In refractory CC we found increased mucosal numbers of MAIT cells, CD4(+) and CD8(+) T cells compared to au-CC. DiscussionPatients with active collagenous colitis have lower percentages of circulating MAIT and NK cells. However, there was no change of these cells in the colonic mucosa. Most mucosal cell populations were increased in budesonide refractory as compared to au-CC patients, particularly the number of MAIT cells. This may indicate that T cell targeting therapy could be an alternative in budesonide refractory CC.

Iron deficiency, defined as ferritin <100 µg/L or ferritin 100-299 µg/L if the transferrin saturation is <20 %, with or without anaemia is a common comorbidity in patients with acute and chronic heart failure. International and Swedish guidelines recommend treatment of iron deficiency with intravenous iron in patients with symptomatic heart failure and ejection fraction <50 %. Controlled studies document positive effects from treatment with iron carboxymaltose on symptoms, quality of life, functional parameters and risk of hospitalisation. We present a simple algoritm based on published data to help the responsible physician to manage these patients in clinical practice., Hos patienter med akut och kronisk hjärtsvikt utgör järnbrist med eller utan samtidig anemi en vanlig komorbiditet kopplad till sämre funktionsklass och prognos. Vid hjärtsvikt definieras järnbrist som ferritin <100µg/l eller som ferritin 100–299 µg/l om transferrinmättnaden samtidigt är <20 procent. Svenska och internationella riktlinjer rekommenderar utredning (blodstatus, ferritin och transferrinmättnad) och behandling av järnbrist hos patienter med symtomatisk hjärtsvikt och reducerad ejektionsfraktion (<50 procent). Genomförda studier dokumenterar positiva effekter av intravenös behandling med järnkarboximaltos (Ferinject) på symtom, livskvalitet, funktionella variabler och risk för sjukhusvård för hjärtsvikt. Pågående studier undersöker effekterna avseende mortalitet och effekterna vid hjärtsvikt med bevarad ejektionsfraktion (>50 procent) samt effekterna av järnderisomaltos (Monofer). Ansvarig läkare ska ta ställning till utredning av bakomliggande orsak till järnbristen mot bakgrund av patientens allmäntillstånd och hjärtstatus.

Background and Aims: Patient-reported outcome measures [PROMs] aim to measure patients' perception of how their disorder influences everyday functioning. The objective of this study was to develop a PROM to assess disease activity in microscopic colitis [MC] fulfilling the requirements of the Food and Drug Administration [FDA]. Methods: The European Microscopic Colitis Activity Index [E-MCAI] was developed in four steps. [1] A list of symptoms associated with active MC was created by a group of experts in the field. [2] Content validity of the symptoms was performed by experts [n = 14] and patients [n = 79] using the Content Validity Index. [3] Questions and response alternatives were created for each symptom, and validity of the E-MCAI was evaluated with cognitive interviews with patients [n = 7] and by the experts. [4] A pilot postal survey was performed to ensure usability. Results: Seven of the symptoms related to active MC fulfilled the criteria for content validity and were included in the E-MCAI: stool consistency, stool frequency, stools at night, feel a need to pass more stools shortly after a bowel movement, urgent need to empty the bowel, leakage of stool and abdominal pain. The development and validation process resulted in the current version of the E-MCAI consisting of six questions related to MC. Conclusions: The E-MCAI was developed using the methods advocated by the FDA. The evaluation indicates good content validity. Further evaluation will be performed to achieve construct validity, reliability and responsiveness in future cross-sectional and longitudinal studies.

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 Crohn's 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:Julins FoundationBengt Ihre FellowshipMagtarmfonden

Luiza Moraes Holst,1 Jonas Halfvarson,2 Marie Carlson,3 Charlotte Hedin,4 Robert Kruse,5 Carl Mårten Lindqvist,6 Daniel Bergemalm,2 Sven Almér,4 Francesca Bresso,7 Maria Ling Lundström,3 Dirk Repsilber,6 Mauro D’Amato,8– 10 Åsa Keita,11 Henrik Hjortswang,12 Johan Söderholm,11 Johanna Sundin,13 Hans Törnblom,14 Magnus Simrén,14,15 Hans Strid,16 Maria K Magnusson,1 Lena Öhman1 1Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 3Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 4Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden; 5Department of Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 6School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 7Karolinska University Hospital, Gastroenterology Unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden; 8Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; 9IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; 10Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain; 11Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; 12Department of Clinical and Experimental Science, Linköping University, Linköping, Sweden; 13Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden; 14Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 15Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 16Department of Internal Medicine, Södra Älvsborg Hospital

Background and Aims: Patient-reported outcome measures [PROMs] aim to measure patients perception of how their disorder influences everyday functioning. The objective of this study was to develop a PROM to assess disease activity in microscopic colitis [MC] fulfilling the requirements of the Food and Drug Administration [FDA]. Methods: The European Microscopic Colitis Activity Index [E-MCAT] was developed in four steps. [1] A list of symptoms associated with active MC was created by a group of experts in the field. [2] Content validity of the symptoms was performed by experts [n= 14] and patients [n = 79] using the Content Validity Index. [3] Questions and response alternatives were created for each symptom, and validity of the E-MCAI was evaluated with cognitive interviews with patients [n= 7] and by the experts. [4] A pilot postal survey was performed to ensure usability. Results: Seven of the symptoms related to active MC fulfilled the criteria for content validity and were included in the E-MCAI: stool consistency, stool frequency, stools at night, feel a need to pass more stools shortly after a bowel movement, urgent need to empty the bowel, leakage of stool and abdominal pain.The development and validation process resulted in the current version of the E-MCAI consisting of six questions related to MC. Conclusions: The E-MCAI was developed using the methods advocated by the FDA.The evaluation indicates good content validity. Further evaluation will be performed to achieve construct validity, reliability and responsiveness in future cross-sectional and longitudinal studies., Funding Agencies: Tillotts Pharma; N-ECCO research grants