Das Spektrum der medikamentösen Therapie chronisch-entzündlicher Darmerkrankungen wird immer komplexer, da laufend neue Substanzen nach entsprechendem Wirknachweis zugelassen werden und auf den Markt kommen. Die Leitlinien der DGVS und der ECCO müssen rascher denn je aktualisiert werden, sind aber trotzdem nicht immer auf dem neuesten Stand und bieten nach wie vor keine Priorisierung der Therapieoptionen. Dieses Update geht nach einem Blick auf die Verlaufsdiagnostik auf die aktuell neuen Therapeutika ein, sowie auf die Wirkstoffe in der „Pipeline“.

Schlüsselwörter chronisch-entzündliche Darmerkrankungen - CED - Diagnose - Therapie - Remission - Remissionserhaltung

INTRODUCTION:The STRIDE consensus intends to complement the clinical endpoint with an endoscopic endpoint of mucosal healing and others as treatment targets in ulcerative colitis. If these targets are not reached, STRIDE requires dose or timing adjustments or switching the medication. This narrative review provides a critique of this concept. AREAS COVERED:We analyze and discuss the limitations of current endpoints as targets, their currently limited achievability, and the lacking evidence from controlled trials relating to 'treat to target.' The relevant publications in PubMed were identified in a literature review with the key word 'ulcerative colitis.' EXPERT OPINION:In ulcerative colitis, the standard clinical target is measured traditionally by the MAYO-score, but in variable combinations of patient and physician reported outcomes as well as also different definitions of the endoscopic part. Only a score of 0 is more stringent than clinical remission but is only achieved by a minority of patients in first and even less in second line therapy. The concept is not based on clear evidence that patients indeed benefit from appropriate escalation of treatment. Until the STRIDE approach is proven to be superior to standard treatment focusing on clinical well-being, the field should remain reluctant.

ABSTRACT Introduction Most guidelines for IBD still recommend step-by-step therapy with initially classic drugs such aminosalicylates (in ulcerative colitis) or steroids but avoid prioritizing certain biological drugs and JAK inhibitors in the complicated course. This review provides an aid to pending therapy decisions. Areas covered In this review, we analyze the evidence for Crohn’s disease as well as ulcerative colitis in order to optimize and ‘personalize’ the choice of therapy, especially in difficult cases. The relevant publications in Pubmed were identified in a continuous literature review with the key words ‘Crohn´s disease’ and ‘ulcerative colitis.’ Expert opinion Based on this complex data set following standard therapies steroid-refractory Crohn´s disease should preferentially be treated with combined infliximab plus azathioprine or risankizumab, in second line after their failure with ustekinumab or adalimumab. In steroid-refractory ulcerative colitis infliximab plus azathioprine or upadacitinib should be preferred in first line, filgotinib, tofacitinib or ustekinumab in second line. A steroid-dependent course in both diseases requires azathioprine or vedolizumab, in second line infliximab or Janus kinase inhibitors. The conclusions drawn from these complex data may be helpful for individual decision making in daily clinical practice.

Introduction: The STRIDE consensus suggested to focus on mucosal healing, based on biomarkers and endoscopy, in addition to clinical endpoints as treatment target. This narrative review provides a critique of this concept in Crohn's disease.Areas covered: We analyze and discuss the limitations of endpoints as targets, their currently limited achievability, and the controversial evidence relating to 'treat to target.' The relevant publications in Pubmed were identified in a literature review with the key word 'Crohn's disease.'Expert opinion: All targets and endpoints have their limitations, and, even if reached, not all have unequivocally been shown to improve prognosis. The major deficiency of STRIDE is not only the lack of validation and agreement upon endpoints but little evidence of their achievability in a sizable proportion of patients by dose or timing adjustments or switching the medication. Above all, the concept should be based on clear evidence that patients indeed benefit from appropriate escalation of treatment and relevant controlled studies in this regard have been controversial. Until the STRIDE approach is proven to be superior to standard treatment focusing on clinical well-being, the field should remain reluctant and expect more convincing evidence before new targets are approved.

Introduction: SARS-CoV-2 infected patients with cancer have a worse outcome including a significant higher mortality, compared to non-cancer patients. However, limited data are available regarding in-hospital mortality during the Omicron phase of the pandemic. Therefore, the aim of the study was the comparison of mortality in patients with history of cancer and patients with active cancer disease during the different phases of the COVID-19 pandemic, focusing on the current Omicron variant of concern. Methods: We conducted a multicenter, observational, epidemiological cohort study at 45 hospitals in Germany. Until July 20, 2022, all adult hospitalized SARS-CoV-2 positive patients were included. The primary endpoint was in-hospital mortality regarding cancer status (history of cancer and active cancer disease) and SARS-CoV-2 virus type. Results: From March 11, 2020, to July 20, 2022, a total of 27,490 adult SARS-CoV-2 positive patients were included in the study. 2,578 patients (9.4%) had diagnosis of cancer, of whom 1,065 (41.3%) had history of cancer, whereas 1,513 (58.7%) had active cancer disease. Overall 3,749 out of the total of 27,490 patients (13.6%) died during the hospital stay. Patients with active cancer disease had a significantly higher mortality compared to patients without cancer diagnosis, in both phases of the pandemic (wild-type to Delta: OR 1.940 [1.646–2.285]); Omicron: 2.864 [2.354–3.486]). After adjustment to co-variables, SARS-CoV-2 infected patients with active cancer disease had the highest risk for in-hospital mortality compared to the other groups, in both phases of the pandemic. Conclusion: The CORONA Germany study indicates that hospitalized patients with active cancer disease are at high risk of death during a SARS-CoV-2 infection. Mortality of patients with history of cancer improved to nearly the level of non-cancer patients during Omicron phase.

BACKGROUND:Dementia has been identified as a major predictor of mortality associated with COVID-19.OBJECTIVE:The objective of this study was to investigate the association between dementia and mortality in COVID-19 inpatients in Germany across a longer interval during the pandemic.METHODS:This retrospective study was based on anonymized data from 50 hospitals in Germany and included patients with a confirmed COVID-19 diagnosis hospitalized between March 11, 2020 and July, 20, 2022. The main outcome of the study was the association of mortality during inpatient stays with dementia diagnosis, which was studied using multivariable logistic regression adjusted for age, sex, and comorbidities as well as univariate logistic regression for matched pairs.RESULTS:Of 28,311 patients diagnosed with COVID-19, 11.3% had a diagnosis of dementia. Prior to matching, 26.5% of dementia patients and 11.5% of non-dementia patients died; the difference decreased to 26.5% of dementia versus 21.7% of non-dementia patients within the matched pairs (n = 3,317). This corresponded to an increase in the risk of death associated with dementia (OR = 1.33; 95% CI: 1.16-1.46) in the univariate regression conducted for matched pairs.CONCLUSION:Although dementia was associated with COVID-19 mortality, the association was weaker than in previously published studies. Further studies are needed to better understand whether and how pre-existing neuropsychiatric conditions such as dementia may impact the course and outcome of COVID-19.

Background Machine learning (ML) algorithms have been trained to early predict critical in-hospital events from COVID-19 using patient data at admission, but little is known on how their performance compares with each other and/or with statistical logistic regression (LR). This prospective multicentre cohort study compares the performance of a LR and five ML models on the contribution of influencing predictors and predictor-to-event relationships on prediction model´s performance. Methods We used 25 baseline variables of 490 COVID-19 patients admitted to 8 hospitals in Germany (March–November 2020) to develop and validate (75/25 random-split) 3 linear (L1 and L2 penalty, elastic net [EN]) and 2 non-linear (support vector machine [SVM] with radial kernel, random forest [RF]) ML approaches for predicting critical events defined by intensive care unit transfer, invasive ventilation and/or death (composite end-point: 181 patients). Models were compared for performance (area-under-the-receiver-operating characteristic-curve [AUC], Brier score) and predictor importance (performance-loss metrics, partial-dependence profiles). Results Models performed close with a small benefit for LR (utilizing restricted cubic splines for non-linearity) and RF (AUC means: 0.763–0.731 [RF–L1]); Brier scores: 0.184–0.197 [LR–L1]). Top ranked predictor variables (consistently highest importance: C-reactive protein) were largely identical across models, except creatinine, which exhibited marginal (L1, L2, EN, SVM) or high/non-linear effects (LR, RF) on events. Conclusions Although the LR and ML models analysed showed no strong differences in performance and the most influencing predictors for COVID-19-related event prediction, our results indicate a predictive benefit from taking account for non-linear predictor-to-event relationships and effects. Future efforts should focus on leveraging data-driven ML technologies from static towards dynamic modelling solutions that continuously learn and adapt to changes in data environments during the evolving pandemic. Trial registration number : NCT04659187.

Schlüsselwörter extraintestinale Manifestation - intraepitheliale Neoplasie - intestinale Komplikation - Immunsuppressiva - Primäre Sklerosierende Cholangitis

Durch die Einführung der „Biologika“, das heißt monoklonaler Antikörper gegen verschiedene Zielstrukturen, wie Tumornekrosefaktor (TNF), Integrinen oder Interleukin 12/23 ist die Therapie der chronisch entzündlichen Darmerkrankung (CED, ▶Abb. 1, ▶Abb. 2) immer komplexer und parenteral geworden [1]. Nunmehr rücken aber verstärkt orale Medikamente mit einem neuen Angriffspunkt, den Januskinasen (ursprünglich „just another kinase“, JAK) in den Fokus. Sie liefern die Kinaseaktivität für Zytokinrezeptoren, phosphorylieren sich gegenseitig sowie auch die STAT(signal transducer and activator of transcription)-Proteine. Letztere wandern als Transkriptionsfaktoren zum Zellkern und aktivieren – in der Regel proinflammatorische – Zielgene [2]. Mehrere oral verfügbare JAK-Inhibitoren stehen als neuere antiinflammatorische Substanzen zur Verfügung, die sich durch ihre Spezifität für die JAK-Typen 1–3 beziehungsweise Tyrosinkinase-2 (TYK2) unterscheiden. Zugelassen sind sie für rheumatoide Arthritis (RA), Psoriasis und Colitis ulcerosa [3]. Eine Übersicht der Studienlage zeigt ▶Tab. 1.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study