Abstract Background In this real-world-evidence (RWE) study we aimed to analyse the persistence of biologic therapy in biologic-naïve ulcerative colitis (UC) patients and to compare 1-year effectiveness of vedolizumab (VDZ) and anti-TNF. Methods Between 2017 and 2020, 1200 consecutively enrolled biologic-naïve and biologic- experienced patients with UC and Crohn′s disease (CD) were prospectively included in the VEDOIBD-Registry from 45 IBD-experienced centres across Germany. After exclusion of bio-experienced patients, CD and missing outcomes, the final sample consisted of 274 biologic-naïve UC-patients with 1-year follow-up data. Switchers of a drug were considered as treatment failure (modified intention-to-treat analysis; mITT) while switchers were excluded from per protocol analysis (PP). Clinical response modified (reduction of partial Mayo score (pMayo) from baseline to 1-year by >3 points or a reduction of at least 30% compared to baseline or reaching remission at 1-year) and (steroid-free) remission rates (pMayo ≤1 plus a bleeding subscore=0 (and no systemic use of steroids or budesonide at 1-year)) were predefined as outcomes. To reduce the effect of confounders, PS adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Results 158 VDZ and 116 anti-TNF (ADA: 27.6%, IFX: 57.8%, GOL: 14.7%) biologic-naïve UC-patients were included in this prospective RWE comparing the effectiveness of VDZ vs anti-TNF. Until week 52 significantly more patients switched to another biologic-drug in the anti-TNF group than in the VDZ group (40.5% vs 16.5%; p<0.001) (Fig. 1). In mITT, clinical response at 1-year was significantly higher in VDZ than in anti-TNF treated patients (61.7% vs. 40.3%; OR 2.39 (95% CI 1.39–4.10)). VDZ also tended to be superior to anti-TNF for (steroid-free) remission (Tab. 1; p=0.058 (p=0.051)). In the PP-analysis, VDZ showed numerically higher 1-year effectiveness, but this did not reach statistical significance (Tab. 1). Analysing week-14 induction phase responders (Tab. 2), VDZ had numerically higher effectiveness rates compared to anti-TNF but without significant difference. Conclusion The 1-year maintenance findings suggested, in line with our previous induction phase data, only moderate long-term effectiveness in both groups. However, besides the significant response data, VDZ showed numerically higher remission rates compared to anti-TNF though only borderline significant. The higher treatment persistence of VDZ vs anti-TNF, along with the higher effectiveness, may suggest VDZ as a first-line biologic therapy option in UC patients.

Abstract Background To gain insight into vedolizumab (VDZ) use as a first-line biologic in Crohn′s Disease (CD), this real-world study aimed to assess, within the maintenance phase, the 1-year comparative effectiveness and persistence of VDZ vs anti-TNF therapy in biologic-naïve CD-patients. Methods Between 2017–2020, 1200 consecutively enrolled biologic-naïve and biologic-experienced patients with ulcerative colitis (UC) and CD were prospectively included in the VEDOIBD-Registry from 45 IBD-experienced centres across Germany. 294 biologic-naïve CD-patients starting a new therapy with VDZ or anti-TNF (adalimumab: ADA or infliximab: IFX) were included in this real-world evidence (RWE) study. The Kaplan-Meier was used to summarize the treatment persistence from the start of therapy through week-52. The primary outcome was week-52 clinical remission (HBI ≤ 4). Patients were analyzed on a modified intent-to-treat basis (mITT; switchers considered as outcome failure) and on a per-protocol (PP) basis (excluding switchers). To reduce selection bias in the estimation of treatment effects, the inverse probability of treatment weighting propensity score (PS) was implemented. A weighted logistic regression was used to evaluate the effectiveness. The results were reported as odds ratio (OR) and 95% confidence interval (CI). Results 71 VDZ and 223 anti-TNF (ADA: 59.6%, IFX: 40.4%) biologic-naïve CD-patients were evaluated. 52-weeks after treatment initiation approximately 94% of VDZ patients were still in continuous treatment vs 75% of ADA and 78% of IFX (Figure 1). The mITT 1-year clinical remission rate was 76.1% for VDZ vs 63.8% for anti-TNF (OR: 1.80, 95% CI: 0.86–3.76). Similar results were observed for VDZ vs IFX (Table 1). In contrast, the clinical remission was significantly higher in the VDZ group than in the ADA group (OR: 2.24, 95% CI: 1.04–4.85). The PP analysis suggested comparative effectiveness, having excluded more anti-TNF switchers. 91.7% of week-14 responders VDZ patients were in clinical remission from week 14 through 52 vs 66.1% of anti-TNF patients (OR: 5.69, 95% CI: 1.66–19.5). Similar, significant, results were observed for VDZ vs ADA and for VDZ vs IFX (Table 2). Conclusion In this real-world setting comparing VDZ and anti-TNF in biologic-naïve patients via PS weighted analysis, VDZ showed especially in week-14 responders higher clinical remission rates in comparison to anti-TNF. The higher treatment persistence observed for VDZ, perhaps due to a more favourable safety profile vs anti-TNF, may be considered the main driver for the better effectiveness of VDZ at one year. These findings may aid physicians’ decision-making on the choice of VDZ as the first-line biologic for CD.

Background: Programing of body composition during intrauterine growth may contribute to the higher risk for cardio-metabolic disease in individuals born small or large for gestational age (SGA, LGA). Compensations of intrauterine growth by catch-up or catch-down postnatal growth may lead to adverse consequences like a thin-fat phenotype. Methods: The impact of (i) birth weight as well as (ii) the interaction between birth weight and catch-up or catch-down growth during the first 2 years of life on fat-free mass index (FFMI) and fat mass index (FMI) in 3,204 5–7-year-old children were investigated using Hattori’s body composition chart. Body composition results were compared to appropriate for gestational age (AGA) birth weight with the same body mass index (BMI). Results: In total, 299 children at age 5–7 years were categorized as SGA, 2,583 as AGA, and 322 as LGA. When compared to AGA-children, BMI at 5–7 years of age was higher in LGA-children (15.5 vs. 16.2 kg/m²; p < 0.001) but not different in SGA-children. Compared to AGA with the same BMI, LGA was associated with higher FMI and a lower FFMI in 5–7-year-old girls. This phenotype was also seen for both sexes with catch-down growth during the first 2 years of life whereas catch-up growth prevented the higher FMI and lower FFMI per BMI. By contrast, SGA was associated with a higher FFMI and lower FMI in 5–7-year-old boys compared to AGA boys with the same BMI. This phenotype was also seen with catch-down growth in both genders whereas catch-up growth in girls led to more gain in FMI per BMI. Conclusion: LGA with a compensatory catch-down postnatal growth may be a risk factor for the development of disproportionate gain in fat over lean mass whereas SGA with a catch-down postnatal growth seems to favor the subsequent accretion of lean over fat mass. A higher propensity of lean mass accretion during postnatal growth in boys compared to girls explains sex differences in these phenotypes.

Abstract Background IBD-care may be challenging and benefits from a multidisciplinary, cross-sectoral treatment approach and active patient involvement. However, occasionally there is a lack of patients′ empowerment and additionally, a necessity for the optimisation of physicians′ treatment is apparent. Furthermore, there is a deficiency in evidence regarding the effectiveness of structured care approaches (“managed care”) on patient-related outcomes (PROs). Therefore, our study aims to evaluate the potential of managed care programmes for IBD patients. Methods EASEIBD is a cross-border study conducted by IBD-DACH, an IBD working group in Germany (D), Austria (A) and Switzerland (Ch). Within the DACH-region, a cross-sectional survey of patients and physicians from IBD hospital-outpatient departments and gastroenterology practices was carried out. The questionnaire evaluated the effect of instruments and contextual factors of IBD-care with regard to quality of life (QoL). Additionally, the effects of “managed care” instruments were examined while considering centre-related structural characteristics. The analysis was performed using a multivariate multilevel regression model, controlled by various physician and patient characteristics. Results 2536 IBD-patients from 66 centres (643 IBD-patients/quarter; 31% hospital out-patient departments) were consecutively enrolled in EASEIBD (centres/IBD-pat.: D-52/1735; A-10/647; Ch-4/154). Overall, patient satisfaction (77-84%) (Fig. 1) as well as perceived quality of care (82-87%) (Fig. 2) was high and comparable in the descriptive analysis between German, Austrian and Swiss IBD-patients. Statistically significant differences were only found in single characteristics, e.g. in quality of life (EQ5D-VAS) (p=0.004) (Fig. 3). However, these do not appear clinically relevant with regard to the absolute values. In the entire DACH-region there were detectable effects of elements representing structural quality and assessments of the centres, with regard to the perceived quality of patient care (Fig. 4), whereby, in particular, a positive influence of web-based instruments (e.g. homepage) (p=0.040) and potential use of homecare calprotectin (0.046) had the most pronounced effect. Noteworthy, in Germany, the implementation of specialised IBD nurses was associated with a beneficial impact on patients′ QoL (0.027) when compared to the cumulative results from the entire DACH region (p=0.681). Conclusion Our study shows that the use of elements of managed care programmes resulted in a high process quality, which is evident from the reported high patient satisfaction and quality of care by IBD-patients in the entire DACH region, and qualifies this area as a suitable common study landscape.

Abstract Background Prospective, observational real world studies on the effectiveness and safety of ustekinumab (UST) in Crohn’s disease (CD) are required in addition to RCTs, usually confined to selected patients, which may not represent special treatment patterns and everyday clinical practice. The aim of the present 3-year RUN-CD study was to investigate the induction phase effectiveness of UST vs. other biologics (OB) in CD in terms of clinical and steroid-free remission at week 16. To the best of our knowledge, RUN-CD is currently the largest prospective real world evidence (RWE) study with UST in CD using propensity score adjustment. Methods Between 2017–2020, 901 CD-patients starting a new therapy with UST or OB, were enrolled in 44 IBD-experienced centers across Germany. After exclusion of missing outcomes, the final sample consisted of 657 patients. Clinical remission (HBI ≤ 4), and steroid-free remission (HBI ≤ 4 and no systemic use of steroids or budesonide during the last 8 weeks) were considered as outcomes at week 16. To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Results 339 UST (naïve: 34) and 318 OB CD-patients were included (ADA: 50.3%, IFX: 37.4%, VDZ: 12.3%) (naïve: 203). PS removed systematic differences between both groups (30.8% smokers, 15.1% perianal disease, 36.2% surgical resection, 40.5% EIM). The effectiveness of UST for clinical and steroid-free remission was comparable to that of OB at week 16. Besides, in bio-naïve patients, clinical remission was numerically, though not significantly, higher in UST vs OB (Table 1). Similar results were observed in the bio-experienced UST vs. OB groups [remission: 59.3% vs 55.4%; OR: 1.17 (0.73–1.90)]. For both the remission rates were higher in the bio-naïve than in the bio-experienced groups (p&amp;lt;0.05 for both). Conclusion In this prospective RUN-CD study, with propensity score weighted groups, UST showed similar induction effectiveness in comparison with OB therapies. Remarkably higher remission rates were observed in this RWE study than in prior RCTs. An additional favorable safety profile supports consideration of UST as a first-line targeted therapy for CD.

We characterized the profile of Crohn's disease (CD) or ulcerative colitis (UC) biologic-naïve patients (starting a new therapy with vedolizumab or TNFα-antagonists), their baseline disease activity predictors, and their perception of the quality of life (HRQoL). The VEDOIBD-Study is a real-world study on the effectiveness of vedolizumab vs other biologics as induction and maintenance therapy for CD and UC. A total of 627 CD and 546 UC patients were enrolled from IBD-experienced centers across Germany. In both biologic-naïve vedolizumab (n=397) and anti-TNF (n=359) patients, CD and UC disease severity and HRQoL predictors were analyzed with logistic regression. The results were reported as odds ratio (OR) and 95% confidence interval (CI). When compared to biologic-naïve anti-TNF patients, a first biological therapy with vedolizumab was considered for older CD patients, with a less complicated though longer disease course, and with a history of comorbidities. No differences in (unmet) needs were observed among patients with UC. The presence of extra-intestinal manifestations in biologic-naïve anti-TNF patients with CD (OR (95% CI): 3.83 (1.69-8.68)) and, in both biologic-naïve groups of patients with UC, stool frequency (2.00 (1.25-3.19); 1.82 (1.10-3.02), respectively) and rectal bleeding (2.24 (1.20-4.18); 1.92 (1.19-3.11), respectively) emerged as the most important predictors of disease severity, which in turn were also significantly associated with a worse HRQoL. This study highlights the existence of unmet medical needs of patients with CD or UC, for whom a new biological therapy is planned as part of the VEDOIBD-Study, which considerably impacts their HRQoL.

Introduction: Body composition assessment is superior to the use of body mass index (BMI) to characterize the nutritional status in pediatric populations. For data interpretation, suitable reference data are needed; hence, we aimed to generate age-dependent and sex-specific body composition reference data in a larger population of children and adolescents in Germany. Methods: This is a cross-sectional study on a representative group of 15,392 5- to 17-year-old children and adolescents. Body composition was assessed by bioelectrical impedance analysis using a population-specific algorithm validated against air displacement plethysmography. Age- and sex-specific percentiles for BMI, fat mass index (FMI), fat-free mass index (FFMI), and a “load-capacity model” (characterized by the ratios of fat mass [FM]/ fatt-free mass [FFM] and FM/FFM²) were modeled using the LMS method. Results: BMI, FMI, FFMI, FM/FFM, and FM/FFM² curves showed similar shapes between boys and girls with steady increases in BMI, FMI, and FFMI, while FM/FFM²-centiles decreased during early childhood and adolescence. Sex differences were observed in FMI and FM/FFM percentiles with increases in FMI up to age 9 years followed by a steady decrease in FM/FFM during and after puberty with a fast-growing FFMI up to age 17 in boys. The prevalence of low FFM relative to FM reached more than 60% in overweight children and adolescents. Conclusion: These pediatric body composition reference data enable physicians and public health scientists to monitor body composition during growth and development and to interpret individual data. The data point out to an early risk of sarcopenia in overweight children and adolescents.

Metabolomics can be a tool to identify dietary biomarkers. However, reported food-metabolite associations have been inconsistent, and there is a need to explore further associations. Our aims were to confirm previously reported food-metabolite associations and to identify novel food-metabolite associations. We conducted a cross-sectional analysis of data from 849 participants (57% men) of the PopGen cohort. Dietary intake was obtained using FFQ and serum metabolites were profiled by an untargeted metabolomics approach. We conducted a systematic literature search to identify previously reported food-metabolite associations and analyzed these associations using linear regression. To identify potential novel food-metabolite associations, datasets were split into training and test datasets and linear regression models were fitted to the training datasets. Significant food-metabolite associations were evaluated in the test datasets. Models were adjusted for covariates. In the literature, we identified 82 food-metabolite associations. Of these, 44 associations were testable in our data and confirmed associations of coffee with 12 metabolites, of fish with five, of chocolate with two, of alcohol with four, and of butter, poultry and wine with one metabolite each. We did not identify novel food-metabolite associations; however, some associations were sex-specific. Potential use of some metabolites as biomarkers should consider sex differences in metabolism.