Upadacitinib in Crohn's disease.

INTRODUCTION: The small molecule and oral selective and reversible Janus kinase (JAK) inhibitor upadacitinib has been approved for the treatment of moderate to severe active Crohn's disease (CD) in adult patients since April 2023 by EMA/FDA. AREAS COVERED: The approval is based on the two induction studies a maintenance study showing that upadacitinib induction and maintenance therapy was superior to placebo. The approval of upadacitinib in CD expands the therapeutic armamentarium for the management of inflammatory bowel diseases (IBD). Upadacitinib is the first and only JAK inhibitor approved in patients with CD and provides a novel mechanism of action and the first advanced oral treatment option for patients with CD. Upadacitinib is approved for the treatment of other immunologically mediated disorders, including ulcerative colitis, rheumatoid arthritis, psoriasis arthritis, axial spondylarthritis, ankylosing spondylitis, and atopic dermatitis. Treatment of atopic dermatitis has been approved from the age of 12 years. EXPERT OPINION: Upadacitinib may cause relevant changes of our current treatment algorithms for Crohn's disease. Further real-world studies and head-to-head comparisons are needed to position upadacitinib in our current treatment algorithms for CD.

[Biologics in inflammatory bowel diseases]. / Biologika bei chronisch-entzündlichen Darmerkrankungen.

BACKGROUND: In addition to conventional anti-inflammatory treatment for chronic inflammatory bowel disease (IBD), there has been an evolution of new treatment options over the past 20 years. Already approved biologics provide multiple treatment alternatives but also make the treatment algorithms more complex. This development results in a substantial improvement in patient care. The ambitious treatment targets are associated with a higher quality of life and the reduction of long-term disability and morbidity. OBJECTIVE: The aim of this article is to give an overview of how biologics can currently be implemented in IBD. In particular, the current clinical management is presented and an outlook on future treatment options with biologics for IBD is provided. MATERIAL AND METHODS: A search was carried out in PubMed and ClinicalTrials.gov and the current German and European guidelines and expert recommendations were evaluated. RESULTS: Since the late 1990s there have been a continuously increasing number of treatment options for IBD. All substances have proven safety and efficacy in large randomized clinical studies and enable increasingly more individualized treatment for patients with IBD. Biologics are currently the standard treatment of choice for moderate to severe inflammatory activity as well as for steroid-refractory or steroid-dependent courses of disease after failure of conventional treatment. CONCLUSION: The diversity of IBD treatment offers increasing treatment options and thus improved patient care; however, as the number of new substances increases treatment becomes more complex. This article summarizes the current and future treatment options for IBD and their integration into current treatment algorithms.

Moderate endurance and muscle training is beneficial and safe in patients with quiescent or mildly active Crohn's disease.

BACKGROUND AND AIMS: Physical activity is beneficial in several chronic disorders including Crohn's disease, but the preferred type of exercise is unknown. Our study aimed to examine and compare the safety, feasibility and potential beneficial effects of individual moderate endurance and moderate muscle training in patients with Crohn's disease. METHODS: Quiescent or mildly active (Crohn's disease activity index <220) patients with Crohn's disease were randomly allocated to either a control, endurance, or muscle training group. Participants exercised individually for 3 months three times per week. Endpoints included dropout rate, disease activity, inflammatory parameters including faecal calprotectin, anthropometric data, quality of life, physical activity and strength. RESULTS: A total of 45 patients with Crohn's disease were randomly allocated. In the endurance group (n = 17), the dropout rate was significantly higher (47% vs. 13%) compared with the muscle group (n = 15). In both groups the maximal and average strength in the upper and lower extremities increased significantly (all P < 0.04). In the endurance group emotional function was significantly improved (P = 0.03). Statistically significant changes of disease activity and other outcome parameters were not observed in this pilot cohort. CONCLUSION: Both individual moderate endurance and muscle training can be safely performed in patients with mild or quiescent Crohn's disease. Muscle training appears more feasible and may be favoured. Both forms of exercise have beneficial effects on strength. Quality of life increased in both intervention groups, although statistical significance was only reached in one subgroup.

A prospective cohort study to assess the relevance of vedolizumab drug level monitoring in IBD patients.

BACKGROUND: Vedolizumab (VDZ) drug monitoring strategies in inflammatory bowel disease (IBD) patients have not been systematically investigated so far. We evaluated the correlation between VDZ trough levels (VTL) and the treatment response in IBD. METHODS: Fifty-one patients with active IBD on or starting a therapy with VDZ were enrolled in this prospective and observational single centre study. Disease activity indices, blood tests, and anthropometric parameters were assessed over a time period of 6 months. One hundred and fifty-five VDZ serum trough levels were measured directly before the next scheduled application using liquid chromatography mass spectrometry (LC-MS/MS). RESULTS: VDZ treatment was found to be clinically effective (Harvey Bradshaw Index (HBI) dropping from 10 to 5.5 points (p < .0005) in Crohn's disease (CD) patients; partial Mayo score (pMS) from 4.4 to 2.1 points (p < .0005) in ulcerative colitis patients (UC). CRP levels tended to decrease and haemoglobin levels to increase under VDZ therapy. CD patients with a serum CRP level lower than 5 mg/l exhibited significantly higher VTL than those with elevated CRP levels (34.9 versus 21.7 µg/ml, p = .00153). UC patients with haemoglobin levels higher 12 g/dl at the time of VTL measurement had significantly higher VTL compared to patients with lower haemoglobin levels (35.4 versus 15.6 µg/ml, p < .0005). CONCLUSIONS: Our data suggest a significant correlation between VTL and response to therapy in IBD patients (higher VTL associated with better response).

Complementary therapies in inflammatory bowel diseases.

Complementary and alternative therapies (CAM) are defined as therapies that are presently not considered part of conventional medical practice. They are termed "complementary" when used in addition to conventional therapies and termed "alternative" when used instead of conventional therapies. CAM includes many different practices, for example Ayurveda, acupuncture or traditional Chinese medicine (TCM), phytotherapy, homeopathy, probiotics and dietary supplements. While some evidence of benefit exists regarding some therapies, for most of these therapeutic approaches, the therapeutic efficacy and safety have not been proven in well-designed scientific studies. However, the use of complementary and alternative medicine among IBD patients is common, and physicians are frequently confronted with questions about their use. As most of the reported studies contain methodological problems, it is often difficult for physicians to inform their patients adequately. Nevertheless, the widespread use of CAM needs to be recognized. Some of these agents exert plausible biological effects in IBD patients and warrant further investigation. Controlled trials in IBD are warranted to show therapeutic benefits and safety of CAM. This review aims to give a brief overview on the current use of various complementary and alternative treatment options in IBD patients.

Correlation of left ventricular wall thickness, heart mass, serological parameters and late gadolinium enhancement in cardiovascular magnetic resonance imaging of myocardial inflammation in an experimental animal model of autoimmune myocarditis.

For a definitive diagnosis of myocarditis, different strategies like analysis of late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR) up to invasive endomyocardial biopsy have been applied. The objective of the study was to investigate inflammatory changes like left ventricular wall thickening and increase of ventricular mass and to quantitatively analyse their correlation with extent and localisation of myocardial damage in CMR and with subsequent changes of serological markers in an animal model of an experimental autoimmune myocarditis (EAM). In the current study, an EAM was induced in 10 male Lewis rats, 10 rats served as control. On day 21, animals were examined with four CMR protocols to assess the extent of LGE in a 12 segment model of the rat heart. Left myocardial wall thickness and mass and histological grade of inflammation were measured to determine localisation and severity of the induced myocarditis. Depending on the CMR sequence, LGE was mostly found in the left anterior (9.6%) and left lateral (8.7%) myocardial wall segments. Wall thickness correlated with the LGE area in CMR imaging and the histopathological severity of myocarditis for the left lateral myocardial wall segment. In a similar way, the heart mass correlated to the extent of LGE for the left lateral segment. We conclude that in our animal model left ventricular wall thickness and mass reflect the severity of myocardial changes in myocarditis and that the EAM rat model is well suited for further investigations of myocarditis.

Accuracy of cardiovascular magnetic resonance in myocarditis: comparison of MR and histological findings in an animal model.

BACKGROUND: Because endomyocardial biopsy has low sensitivity of about 20%, it can be performed near to myocardium that presented as late gadolinium enhancement (LGE) in cardiovascular magnetic resonance (CMR). However the important issue of comparing topography of CMR and histological findings has not yet been investigated. Thus the current study was performed using an animal model of myocarditis. RESULTS: In 10 male Lewis rats experimental autoimmune myocarditis was induced, 10 rats served as control. On day 21 animals were examined by CMR to compare topographic distribution of LGE to histological inflammation. Sensitivity, specificity, positive and negative predictive values for LGE in diagnosing myocarditis were determined for each segment of myocardium. Latter diagnostic values varied widely depending on topographic distribution of LGE and inflammation as well as on the used CMR sequence. Sensitivity of LGE was up to 76% (left lateral myocardium) and positive predictive values were up to 85% (left lateral myocardium), whereas sensitivity and positive predictive value dropped to 0-33% (left inferior myocardium). CONCLUSIONS: Topographic distribution of LGE and histological inflammation seem to influence sensitivity, specificity, positive and negative predictive values. Nevertheless, positive predictive value for LGE of up to 85% indicates that endomyocardial biopsy should be performed "MR-guided". LGE seems to have greater sensitivity than endomyocardial biopsy for the diagnosis of myocarditis.

Acute myocarditis in a rat model: late gadolinium enhancement with histopathological correlation.

The aim of the current study was to use an established animal model of autoimmune myocarditis and to judge the ability of cardiovascular MRI (CMR) in quantitatively measuring the extent of myocardial involvement compared with histopathological measurement of severity and extent. Experimental autoimmune myocarditis (EAM) was induced in 10 male Lewis rats. On day 21, all animals were investigated by CMR to measure the extent of late gadolinium enhancement (LGE). Subsequently, histopathological evaluation of the entire heart was performed. All animals of the experimental group fulfilled histopathological criteria of myocarditis, revealing necrosis in seven of eight cases. At reduced heart rate, area of LGE correlated highly with histologically proven area of myocarditis (r = 0.80-0.87, p < 0.05). LGE was mainly located in the anterior (range 50-62.5%) and lateral (range 62.5-75%) left ventricular wall and septum (range 25-50%) with a midwall to subepicardial accentuation. The LGE pattern found by CMR can be regarded as suggestive of EAM. With cellular necrosis being the main mechanism for LGE we were able to show high correlations between CMR examination results and histopathologically proven areas of myocarditis. Thus we think the current animal model can provide the opportunity for further fundamental research into myocarditis.