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

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

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

Inflammatory bowel disease (IBD) patients with impaired quality of life on biologic therapy benefit from the support of an IBD nurse specialist: Results of a randomised controlled trial in Germany (IBDBIO-ASSIST study).

BACKGROUND: IBDBIO-ASSIST was a randomised controlled trial assessing the efficacy of care provided by IBD nurse specialists in Germany in improving health-related quality of life (QoL) in IBD patients on biologic therapy. AIM: To evaluate patient-related outcomes and economic consequences associated with integrating IBD nurses into usual care. METHODS: We randomly assigned 1086 patients with IBD on biologic therapy to a control group (CG) receiving usual care or an intervention group (IG) receiving additional care from an IBD nurse specialist. The primary outcome was disease-specific QoL (sIBDQ) assessed at 6, 12 and 18 months. RESULTS: At baseline, patients in both groups were highly satisfied with their treatment situation and had relatively high sIBDQ values (range: 1-7; CG: 5.12; IG: 4.92). In the intention-to-treat (ITT) analysis of the overall sample, there was no significant difference in sIBDQ between groups at the assessment time points. However, a per-protocol analysis of patients with impaired QoL at baseline (EQ-VAS < 75 [median]), showed improvement in sIBDQ over 6 months that became significant at month 12 and remained significant through month 18 (baseline: IG 4.24; CG 4.31; 18 months: IG 5.02; CG 4.76; p = 0.017). CONCLUSION: High baseline satisfaction of IBD patients with treatment and the relatively high baseline sIBDQ values may have contributed to the lack of significant difference in sIBDQ scores for the overall sample. However, patients with impaired QoL derived significant benefit from additional care provided by an IBD nurse specialist, leading to meaningful improvements in sIBDQ over the long term.

Mapping from SIBDQ to EQ-5D-5L for patients with inflammatory bowel disease.

OBJECTIVE: Clinical studies commonly use disease-specific measures to assess patients' health-related quality of life. However, economic evaluation often requires preference-based utility index scores to calculate cost per quality-adjusted life-year (QALY). When utility index scores are not directly available, mappings are useful. To our knowledge, no mapping exists for the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Our aim was to develop a mapping from SIBDQ to the EQ-5D-5L index score with German weights for inflammatory bowel disease (IBD) patients. METHODS: We used 3856 observations of 1055 IBD patients who participated in a randomised controlled trial in Germany on the effect of introducing regular appointments with an IBD nurse specialist in addition to standard care with biologics. We considered five data availability scenarios. For each scenario, we estimated different regression and machine learning models: linear mixed-effects regression, mixed-effects Tobit regression, an adjusted limited dependent variable mixture model and a mixed-effects regression forest. We selected the final models with tenfold cross-validation based on a model subset and validated these with observations in a validation subset. RESULTS: For the first four data availability scenarios, we selected mixed-effects Tobit regressions as final models. For the fifth scenario, mixed-effects regression forest performed best. Our findings suggest that the demographic variables age and gender do not improve the mapping, while including SIBDQ subscales, IBD disease type, BMI and smoking status leads to better predictions. CONCLUSION: We developed an algorithm mapping SIBDQ values to EQ-5D-5L index scores for different sets of covariates in IBD patients. It is implemented in the following web application: https://www.bwl.uni-hamburg.de/hcm/forschung/mapping.html .

Real-World Effectiveness of Vedolizumab vs Anti-TNF in Biologic-naïve Crohn's Disease Patients: A 2-year Propensity-score-adjusted Analysis from the VEDOIBD-Study.

BACKGROUND: The aim of this observational, real-world evidence, modified intention-to-treat (mITT) study based on prospectively collected data from the VEDOIBD registry was to compare the effectiveness of vedolizumab (VEDO) vs antitumor necrosis factor (anti-TNF) in biologic-naïve Crohn's disease (CD) patients. METHODS: Between 2017 and 2020, 557 CD patients starting therapy with VEDO or anti-TNF were consecutively enrolled in 45 IBD centers across Germany. Per study protocol, the analysis excluded biologic-experienced patients and those with a missing Harvey-Bradshaw Index score, resulting in a final sample of 327 biologic-naïve CD patients. Clinical remission was measured using the Harvey-Bradshaw Index at the end of induction therapy and after 1 and 2 years. Switching to a different therapy was considered an outcome failure. Propensity score adjustment with inverse probability of treatment weighting was used to correct for confounding. RESULTS: The effectiveness of both VEDO (n = 86) and anti-TNF (n = 241) was remarkably high for induction treatment, but VEDO performed significantly less well than anti-TNF (clinical remission: 56.3% vs 73.9%, P < .05). In contrast, clinical remission after 2 years was significantly better for VEDO compared with anti-TNF (74.2% vs 44.7%; P < .05; odds ratio, 0.45; 95% CI, 0.22-0.94). Remarkably, only 17% of patients switched from VEDO to another biologic vs 44% who received anti-TNF. CONCLUSIONS: The results of this prospective, 2-year, real-world evidence study suggest that the choice of VEDO led to higher remission rates after 2 years compared with anti-TNF. This could support the role of VEDO as a first-line biologic therapy in CD.

Real-world effectiveness of vedolizumab compared to anti-TNF agents in biologic-naïve patients with ulcerative colitis: A two-year propensity-score-adjusted analysis from the prospective, observational VEDOIBD -study.

BACKGROUND: This observational real-world evidence (RWE) study is based on prospectively collected data from the VEDOIBD registry study. AIM: To compare the effectiveness of vedolizumab and anti-TNF agents in biologic-naïve patients with ulcerative colitis (UC) at the end of induction and during maintenance treatment. METHODS: Between 2017 and 2020, we enrolled 512 patients with UC starting therapy with vedolizumab or an anti-TNF agent in 45 IBD centres across Germany. We excluded biologic-experienced patients and those with missing partial Mayo (pMayo) outcomes; this resulted in a final sample of 314 (182 on vedolizumab and 132 on an anti-TNF agent). The primary outcome was clinical remission measured using pMayo score; any switch to a different biologic agent was considered an outcome failure (modified ITT analysis). We used propensity score adjustment with inverse probability of treatment weighting to correct for confounding. RESULTS: During induction therapy, clinical remission was relatively low and similar in vedolizumab- and anti-TNF-treated patients (23% vs. 30.4%, p = 0.204). However, clinical remission rates after two years were significantly higher for vedolizumab-treated patients than those treated with an anti-TNF agent (43.2% vs. 25.8%, p < 0.011). Among patients treated with vedolzumab, 29% switched to other biologics, versus 54% who had received an anti-TNF agent. CONCLUSION: After two years of treatment, vedolizumab resulted in higher remission rates than anti-TNF agents.

Health Status, Quality of Life, Psychosocial Well-being, and Wearables Data of Patients With Active Ulcerative Colitis Receiving Filgotinib Therapy (FilgoColitis Study): Protocol for a Real-world Observational Study.

BACKGROUND: Filgotinib was approved in Germany for treating patients with moderate to severe active ulcerative colitis in November 2021. It represents a preferential Janus kinase 1 inhibitor. The FilgoColitis study began recruiting immediately after approval and aims to assess filgotinib effectiveness under real-world conditions with a particular focus on patient-reported outcomes (PROs). The novelty of the study design is the optional inclusion of 2 innovative wearables, which could provide a new layer of patient-derived data. OBJECTIVE: The study investigates quality of life (QoL) and psychosocial well-being of patients with active ulcerative colitis during long-term exposure to filgotinib. PROs related to QoL and psychometric profiles (fatigue and depression) are collected alongside with disease activity symptom scores. We aim to evaluate physical activity patterns collected by wearables as an addition to traditional PROs, patient-reported health status, and QoL in different phases of disease activity. METHODS: This is a prospective, single-arm, multicentric, noninterventional, observational study with a sample size of 250 patients. QoL is assessed with validated questionnaires: the Short Inflammatory Bowel Disease Questionnaire (sIBDQ) for the disease-specific QoL, the EQ-5D for the general QoL, and the fatigue questionnaire (Inflammatory Bowel Disease-Fatigue [IBD-F]). Physical activity data are collected from patients using wearables (SENS motion leg sensor [accelerometry] and smartwatch, GARMIN vívosmart 4). RESULTS: The enrollment started in December 2021 and was still open at the date of submission. After 6 months of study initiation, 69 patients were enrolled. The study is expected to be completed in June 2026. CONCLUSIONS: Real-world data for novel drugs are important to assess effectiveness outside of highly selected populations represented by randomized controlled trials. We examine whether patients' QoL and other PROs can be supplemented with physical activity patterns measured objectively. Use of wearables with newly defined outcomes represents an additional observational tool for monitoring disease activity in patients with inflammatory bowel disease. TRIAL REGISTRATION: German Clinical Trials Register DRKS00027327; https://drks.de/search/en/trial/DRKS00027327. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42574.

Rates of clinical remission and inadequate response to advanced therapies among patients with ulcerative colitis in Germany.

PURPOSE: Many patients treated for ulcerative colitis (UC) do not achieve clinical remission. This real-world study assessed clinical remission and inadequate response rates among patients with UC in Germany treated with advanced therapies. METHODS: This retrospective chart review included patients with UC newly initiating advanced (index) therapy (anti-TNFα agents, vedolizumab, tofacitinib) from January 2017-September 2019 (index date). Included patients had data for ≥ 12 months before (baseline period) and after the index date (follow-up period). Remission was defined as a partial Mayo score ≤ 1. Indicators of inadequate response were: index therapy discontinuation; therapy adjustments (index therapy dose escalation; augmentation with non-advanced therapies; corticosteroid [CS] use during maintenance therapy); CS dependency (use for ≥ 12 weeks); and UC-related hospitalisation, surgery or emergency department visit. Time to first remission and inadequate response were analyzed using Kaplan-Meier analyses. RESULTS: Among 149 patients with UC (median age: 40 years), 96 (64.4%) were biologic-naïve and 42 (28.2%) received CS at the index date. Within 12 months, 52 patients (47.2%) were in remission; of these, 13 patients (25.0%) received ≥ 1 therapy adjustment. At 12 months, 55 patients (37.6%) had ≥ 1 indicator of an inadequate response. Median time to remission was longer among biologic-experienced vs biologic-naïve patients (24 vs 7 months; p = 0.012). CONCLUSION: Over half of the patients were not in clinical remission after 12 months and more than one-third experienced inadequate response. One-quarter of patients in remission required therapy adjustments. Patients with UC require therapies that are more effective than those currently available to achieve better treatment outcomes.

Evaluation of a downstaging, bidirectional version of the Montreal classification of Crohn's disease: Analysis of 5-year follow-up data from the prospective BioCrohn study.

OBJECTIVE: Under the assumption of irreversibility, the Montreal classification provides a unidirectional assessment of the complications and behaviour of Crohn's disease (CD) that does not allow for downstaging. We examined the use of a bidirectional Montreal classification system that can capture disease regression. DESIGN: From the BioCrohn Registry, an inception cohort of patients with CD for ≤12 months duration was defined and followed up for 5-years. Cumulative probabilities for developing complications were estimated using the Kaplan-Meier method. Potential associations of explanatory variables with disease progression were estimated with Cox regression. RESULTS: Among 393 incident CD patients (of whom 255 completed the entire follow-up), the 5-year cumulative probability of developing complications was 41.5% (15.6% and 25.9% for stricturing and penetrating complications respectively). Perianal disease (hazard ratio [95% confidence interval]: 8.45 [4.74-15.07]) and surgical resection of the intestine (2.71 [1.50-4.92]) in the very early phase of the disease were associated with a higher risk of developing a penetrating complication within the 5-year follow-up. The use of a bidirectional Montreal classification system which can account for disease regression demonstrated that 90% of patients exhibited inflammatory disease behaviour at 5 years, in contrast to 58%, if the hierarchical, unidirectional Montreal classification system was used. CONCLUSION: An additional bidirectional disease behaviour assessment capturing reversed or fully controlled complications may provide a more realistic appraisal of the complexity and unmet needs of patients treated with advanced therapies.

Real-world observational cohort study of treatment patterns and safety outcomes of infliximab biosimilar CT-P13 for the treatment of inflammatory bowel disease (CONNECT-IBD).

BACKGROUND: The objective of this non-interventional, observational prospective cohort study (CONNECT-IBD) was to assess the use of CT-P13 (Inflectra®) in the treatment of patients with Crohn's disease (CD) and ulcerative colitis (UC) in the context of treatment with reference infliximab (IFX; Remicade®). METHODS: Patients (recruited April 2015 to October 2018) at 150 sites across 13 European countries were followed for up to 2 years. Primary outcomes were safety, population characteristics, and drug utilization patterns. Secondary outcomes included clinical assessment of disease activity. Data were analyzed descriptively. RESULTS: Overall, 2543 patients (CD, n = 1676; UC, n = 867) were included. In the CT-P13 cohort (n = 1522), median disease duration was 63 (0-579) months and 30% of patients were IFX naïve; median duration of prior IFX treatment was 5 months. During the observation period, median duration of drug exposure was 14 (0-28) months. 41% of patients reported 912 all-causality treatment-emergent adverse events (TEAEs); 24% experienced treatment-related TEAEs. Most TEAEs were of mild-to-moderate severity. Treatment-emergent serious adverse events were reported by 17% of patients. CONCLUSION: Safety information for CT-P13 in this large study was consistent with the known safety profile for IFX and did not alter the established benefit-risk profile of CT-P13.

Burden of disease among patients with prevalent Crohn's disease: results from a large German sickness fund.

PURPOSE: The aim of this study was to investigate the burden of disease among a real-world cohort of patients with prevalent Crohn's disease (CD) in Germany. METHODS: We conducted a retrospective cohort analysis using administrative claims data from the German AOK PLUS health insurance fund. Continuously insured patients with a CD diagnosis between 01 October 2014 and 31 December 2018 were selected and followed for at least 12 months or longer until death or end of data availability on 31 December 2019. Medication use (biologics, immunosuppressants (IMS), steroids, 5-aminosalicylic acid) was assessed sequentially in the follow-up period. Among patients with no IMS or biologics (advanced therapy), we investigated indicators of active disease and corticosteroid use. RESULTS: Overall, 9284 prevalent CD patients were identified. Within the study period, 14.7% of CD patients were treated with biologics and 11.6% received IMS. Approximately 47% of all prevalent CD patients had mild disease, defined as no advanced therapy and signs of disease activity. Of 6836 (73.6%) patients who did not receive advanced therapy in the follow-up period, 36.3% showed signs of active disease; 40.1% used corticosteroids (including oral budesonide), with 9.9% exhibiting steroid dependency (≥ 1 prescription every 3 months for at least 12 months) in the available follow-up. CONCLUSIONS: This study suggests that there remains a large burden of disease among patients who do not receive IMS or biologics in the real world in Germany. A revision of treatment algorithms of patients in this setting according to the latest guidelines may improve patient outcomes.

Real-world Comparative Effectiveness of Ustekinumab vs Anti-TNF in Crohn's Disease With Propensity Score Adjustment: Induction Phase Results From the Prospective, Observational RUN-CD Study.

BACKGROUND: In addition to randomized controlled trials (RCTs), real-world studies on the effectiveness of ustekinumab (UST) in Crohn's disease (CD) are required inasmuch as RCTs are usually confined to selected patients, which may not represent everyday clinical practice. Within the framework of the prospective real-world RUN-CD registry, a total of approximately 900 CD patients from 44 inflammatory bowel disease centers from all over Germany starting a new therapy with UST or other biologics were screened for a real-world evidence (RWE) comparison of CD patients with UST vs antitumor necrosis factor (TNF). METHODS: A total of 618 CD patients with a nonrandomized biological therapy were qualified for this induction phase effectiveness RUN-CD study of UST vs anti-TNF. To reduce selection bias in estimations of treatment effects, the propensity score with inverse probability of treatment weighting was implemented. The results were reported as odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 339 UST and 279 anti-TNF patients were analyzed. The effectiveness of UST vs anti-TNF in terms of clinical remission (UST 65.4% vs anti-TNF 63.0%; OR, 1.11; 95% CI, 0.71-1.74) and steroid-free remission (UST 51.0% vs anti-TNF 53.8%; OR, 0.94; 95% CI, 0.60-1.47) was comparable at the end of induction therapy. Similar results were observed in the bio-naïve and bio-experienced UST vs anti-TNF groups. For both, the remission rates were higher in the bio-naïve than in the bio-experienced groups (P < .05). CONCLUSIONS: In this prospective, observational RUN-CD study, the RWE head-to-head comparison of UST vs anti-TNF showed similar induction effectiveness in both groups, remarkably higher than those found in prior RCTs.

The higher effectiveness outcome rates observed in patients treated with UST compared with pivotal studies in combination with its known favorable safety profile and an improved HRQoL support UST use as a first-line, advanced therapy in CD.

Real-world outcomes associated with switching to anti-TNFs versus other biologics in Crohn's Disease patients: A retrospective analysis using German claims data.

Background: The positioning of new biologic agents for the treatment of Crohn's disease (CD) following failure of initial anti-tumor necrosis factor (anti-TNF) therapy remains a challenge in the real world. Objectives: This study aims to investigate the real-world outcomes associated with the sequential use of biologics in CD patients that newly initiate anti-TNFs, specifically comparing those that switch to another anti-TNF versus biologics with other modes of action. Design: Retrospective cohort study. Methods: We identified CD patients who newly began anti-TNF therapy between 1 October 2014 and 31 December 2018 using two German claims databases. Patients were classified as within-class switchers (WCS) if they switched to another anti-TNF or outside-class switchers (OCS) if they switched to vedolizumab (VDZ) or ustekinumab (UST). To compare WCS and OCS, baseline covariates were adjusted through inverse probability of treatment weighting (IPTW), and time-to-event analyses were performed using Cox Proportional Hazard regressions. Results from both databases were meta-analyzed using an inverse variance model. Results: Overall, 376 prevalent adult CD patients who initiated anti-TNFs and switched to another biologic were identified. After IPTW, there were 152 and 177 patients in the WCS and OCS group, respectively. WCS were more likely to receive prolonged corticosteroid therapy [hazard ratio (HR): 1.63, 95% confidence interval (CI): 1.17-2.27, p = 0.004], switch a second time to a different biologic (HR: 2.44, 95% CI: 1.63-3.66, p < 0.001), and discontinue treatment (HR: 1.71, 95% CI: 1.25-2.34, p = 0.001) than OCS. Conclusion: This study suggests that CD patients exhibit more favorable outcomes when switching outside the anti-TNF class to VDZ or UST after initial anti-TNF failure than switching to a second anti-TNF. With loss of response to anti-TNFs as a concern in the real world, comparative evidence from claims data assessing sequential use of biologics can help optimize treatment algorithms of patients after anti-TNF failure.

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility.

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.

A novel unconventional T cell population enriched in Crohn's disease.

OBJECTIVE: One of the current hypotheses to explain the proinflammatory immune response in IBD is a dysregulated T cell reaction to yet unknown intestinal antigens. As such, it may be possible to identify disease-associated T cell clonotypes by analysing the peripheral and intestinal T-cell receptor (TCR) repertoire of patients with IBD and controls. DESIGN: We performed bulk TCR repertoire profiling of both the TCR alpha and beta chains using high-throughput sequencing in peripheral blood samples of a total of 244 patients with IBD and healthy controls as well as from matched blood and intestinal tissue of 59 patients with IBD and disease controls. We further characterised specific T cell clonotypes via single-cell RNAseq. RESULTS: We identified a group of clonotypes, characterised by semi-invariant TCR alpha chains, to be significantly enriched in the blood of patients with Crohn's disease (CD) and particularly expanded in the CD8+ T cell population. Single-cell RNAseq data showed an innate-like phenotype of these cells, with a comparable gene expression to unconventional T cells such as mucosal associated invariant T and natural killer T (NKT) cells, but with distinct TCRs. CONCLUSIONS: We identified and characterised a subpopulation of unconventional Crohn-associated invariant T (CAIT) cells. Multiple evidence suggests these cells to be part of the NKT type II population. The potential implications of this population for CD or a subset thereof remain to be elucidated, and the immunophenotype and antigen reactivity of CAIT cells need further investigations in future studies.

Inadequate Response, Treatment Patterns, Health Care Utilization, and Associated Costs in Patients With Ulcerative Colitis: Retrospective Cohort Study Based on German Claims Data.

BACKGROUND: Real-world data regarding response rates in ulcerative colitis treatment are rare, particularly for later lines of therapy. This study aimed to assess continuity of and changes to advanced therapies, as well as costs and specific indicators defining suboptimal therapy. METHODS: German claims data were retrospectively analyzed (January 2014 to June 2019). Patients with ulcerative colitis initiating an advanced therapy (adalimumab, golimumab, infliximab, tofacitinib, vedolizumab) were included. Inadequate response was indicated by therapy discontinuation, switch, escalation, augmentation, corticosteroid dependency, disease-related hospitalization, or surgery. Health care resource utilization (inpatient, outpatient, sick leaves, medication, aids, and remedies) and related costs were assessed from therapy initiation until discontinuation or loss to follow-up. RESULTS: Among 574 patients (median age, 39 years; female sex, 53.5%) who initiated advanced therapies, 458 (79.8%) received an antitumor necrosis factor therapy, 113 (19.7%) vedolizumab, and 3 (0.5%) tofacitinib. After 12 months, 75% had ≥1 indicator for suboptimal therapy. The median time to first indicated inadequate response was 4.8 months. Therapy discontinuation (38%), switching (26%), and prolonged use of steroids (36%) were common within the first year of treatment. In an unadjusted comparison, all-cause total costs per person-year were significantly higher in those who switched vs patients remaining on their therapy (€44,570 vs €36,807; P < .001). CONCLUSIONS: Our study indicates a high prevalence of inadequate response to advanced therapies. Only 25% of patients showed adequate response within 12 months after therapy initiation. Frequent dose and treatment changes were observed. The economic impact of suboptimal therapy in ulcerative colitis is substantial, highlighting the ongoing need for improved treatment strategies.

Clinical predictors for a complicated course of disease in an inception cohort of patients with ulcerative colitis: results from the prospective, observational EPICOL study.

PURPOSE: The clinical course of ulcerative colitis (UC) is highly heterogeneous, with 20 to 30% of patients experiencing chronic disease activity requiring immunosuppressive or biologic therapies. The aim of this study was to identify predictors for a complicated disease course in an inception cohort of patients with UC. METHODS: EPICOL was a prospective, observational, inception cohort (UC diagnosis, ≤ 6 months) study in 311 patients with UC who were naive to immunosuppressants (IS)/biologics. A complicated course of disease was defined as the need for IS and/or biologic treatment (here therapy with a TNF-α antagonist) and/or UC-related hospitalisation. Patients were followed up for 24 months. RESULTS: Of the 307 out of 311 participants (4 patients did not meet the inclusion criteria "confirmed diagnosis of active UC within the last 6 months" (n = 2) and "immunosuppressive-naïve" (n = 2), analysis population), 209 (68.1%) versus 98 (31.9%) had an uncomplicated versus a complicated disease course, respectively. In a multivariate regression analysis, prior use of corticosteroids and prior anaemia were associated with a significantly increased risk for a complicated disease course (2.3- and 1.9-fold increase, respectively; p < 0.001 and p = 0.002). Based on these parameters, a risk model for patient stratification was developed. CONCLUSION: Our study identifies anaemia and an early need for corticosteroids as predictors for a complicated course of disease in an inception cohort of patients with UC. By determining these parameters in routine clinical practice, our results may support the identification of patients who might benefit from early escalation of therapy.

Long-Term Effectiveness of Oral Ferric Maltol vs Intravenous Ferric Carboxymaltose for the Treatment of Iron-Deficiency Anemia in Patients With Inflammatory Bowel Disease: A Randomized Controlled Noninferiority Trial.

BACKGROUND: Iron-deficiency anemia is common in inflammatory bowel disease, requiring oral or intravenous iron replacement therapy. Treatment with standard oral irons is limited by poor absorption and gastrointestinal toxicity. Ferric maltol is an oral iron designed for improved absorption and tolerability. METHODS: In this open-label, phase 3b trial (EudraCT 2015-002496-26 and NCT02680756), adults with nonseverely active inflammatory bowel disease and iron-deficiency anemia (hemoglobin, 8.0-11.0/12.0 g/dL [women/men]; ferritin, <30 ng/mL/<100 ng/mL with transferrin saturation <20%) were randomized to oral ferric maltol 30 mg twice daily or intravenous ferric carboxymaltose given according to each center's standard practice. The primary endpoint was a hemoglobin responder rate (≥2 g/dL increase or normalization) at week 12, with a 20% noninferiority limit in the intent-to-treat and per-protocol populations. RESULTS: For the intent-to-treat (ferric maltol, n = 125/ferric carboxymaltose, n = 125) and per-protocol (n = 78/88) analyses, week 12 responder rates were 67% and 68%, respectively, for ferric maltol vs 84% and 85%, respectively, for ferric carboxymaltose. As the confidence intervals crossed the noninferiority margin, the primary endpoint was not met. Mean hemoglobin increases at weeks 12, 24, and 52 were 2.5 vs 3.0 g/dL, 2.9 vs 2.8 g/dL, and 2.7 vs 2.8 g/dL with ferric maltol vs ferric carboxymaltose. Treatment-emergent adverse events occurred in 59% and 36% of patients, respectively, and resulted in treatment discontinuation in 10% and 3% of patients, respectively. CONCLUSIONS: Ferric maltol achieved clinically relevant increases in hemoglobin but did not show noninferiority vs ferric carboxymaltose at week 12. Both treatments had comparable long-term effectiveness for hemoglobin and ferritin over 52 weeks and were well tolerated.