Publications

BACKGROUND: There are limited data on the role of proactive therapeutic drug monitoring (TDM) of ustekinumab (UST) in patients with inflammatory bowel disease (IBD). This study investigated the efficacy and safety of proactive TDM in IBD patients treated with subcutaneous (sc) UST.

METHODS: This was a retrospective single-center cohort study. Consecutive patients with IBD who received maintenance subcutaneous (sc) UST therapy and underwent TDM from January 2017 to February 2023 were eligible for inclusion. Patients were followed through May 2024 or until drug discontinuation or an IBD-related surgery. Patients underwent either at least one proactive TDM or reactive TDM only. Survival analysis was performed to evaluate drug persistence, defined as no need for drug discontinuation due to loss of response, serious adverse event (SAE) or an IBD-related surgery, and IBD-related hospitalizations.

RESULTS: The study population consisted of 83 patients (proactive TDM, n = 46) of whom 67 (81%) had Crohn's disease. Patients who had at least one proactive TDM had higher drug persistence (Log-rank P < .001) and less IBD-related hospitalization (Log-rank P = .012) compared to patients undergoing only reactive TDM. In multivariable COX proportional hazard regression analysis, at least one proactive TDM was associated with increased drug persistence (hazard ratio [HR]: 5; 95% confidence interval [95% CI], 2-10; P < .001) and decreased IBD-related hospitalization (HR: 0.24; 95% CI, 0.07-0.83; P = .024). There was no SAE reported.

CONCLUSIONS: This retrospective study showed that proactive TDM is associated with increased drug persistence and decreased IBD-related hospitalization in IBD patients treated with sc UST.

Despite growing numbers of women entering medicine, women remain underrepresented in gastroenterology (GI) in the United States and globally, and barriers to equity persist. Prior studies describing gender makeup and ongoing challenges for women in GI have largely reflected the physician experience in the United States (US). In this study by Venezia et al., the authors report the results of a survey conducted among Italian women gastroenterologists. Despite more robust protective laws, including mandatory paid maternity leave, disparities in career trajectory, participation in advanced training opportunities, and academic representation persist. This study suggests that longitudinal policies (including and beyond parental leave) and improved collaboration among women in GI across the globe are needed to achieve equity and parity in our field.

In patients with disorders of gut-brain interaction (DGBI), overlapping non-gastrointestinal conditions such as fibromyalgia, headaches, gynaecological and urological conditions, sleep disturbances and fatigue are common, as is overlap among DGBI in different regions of the gastrointestinal tract. These overlaps strongly influence patient management and outcome. Shared pathophysiology could explain this scenario, but details are not fully understood. This overlap has been shown to be of great relevance for DGBI. In addition, symptoms considered to be caused by a DGBI could have a detectable organic cause, and in patients with a diagnosed organic gastrointestinal disease, symptoms not clearly explained by the pathology defining this organic disease are common. Thus, the aims of this Rome Foundation Working Team Report were to review the literature on overlapping conditions among patients with paediatric and adult DGBI and, based on the available epidemiological and clinical evidence, make recommendations for the current diagnostic and therapeutic approach, and for future research. Specifically, we focused on other DGBI in the same or different gastrointestinal anatomical region(s), DGBI overlap with organic bowel diseases in remission, and DGBI overlap with non-gastrointestinal, non-structural conditions.

BACKGROUND: Therapeutic drug monitoring is important for optimizing anti-tumor necrosis factor-α (TNF-α) therapy in inflammatory bowel disease. However, the exposure-response relationship has never been assessed in pouchitis.

AIMS: To explore associations between anti-TNF-α drug concentration and pouchitis disease activity in patients with a background of ulcerative colitis.

METHODS: A retrospective, multicenter, cross-sectional study was conducted in adult patients with pouchitis requiring anti-TNF-α treatment. Rates of clinical and endoscopic remission were calculated, and drug concentrations during maintenance therapy were compared between remission and non-remission cohorts.

RESULTS: Sixty-three patients were included: median age, 48 years (IQR 36-59) and median time since pouchitis diagnosis, 7 years (IQR 2-13). Patients received infliximab, n = 27 (43%), adalimumab, n = 29 (46%), or both n = 7 (11%). Thirty-two (51%) patients received concomitant immunomodulation. Median infliximab trough concentrations (mg/ml) were similar between patients in clinical remission (n = 21) vs non-remission (n = 11), 5.3 vs. 4.4, p = 0.73. For adalimumab, median drug concentrations did not significantly differ between remission/non-remission groups based on clinical (n = 18/18), 11.4 vs 7.6, p = 0.32, or endoscopic assessment, (n = 7/29), 9.0 vs. 7.8, p = 0.78. Four patients had positive anti-drug antibodies with undetectable drug concentration.

CONCLUSION: In a cohort of patients with pouchitis, higher anti-TNF-α drug concentrations were not associated with more clinical or endoscopic remission.

Microvascular ischemia, especially in the heart and kidneys, is associated with inflammation and metabolic perturbation, resulting in cellular dysfunction and end-organ failure. Heightened production of adenosine from extracellular nucleotides released in response to inflammation results in protective effects, inclusive of adaptations to hypoxia, endothelial cell nitric oxide release with the regulation of vascular tone, and inhibition of platelet aggregation. Purinergic signaling is modulated by ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1)/CD39, which is the dominant factor dictating vascular metabolism of extracellular ATP to adenosine throughout the cardiovascular tissues. Excess levels of extracellular purine metabolites, however, have been associated with metabolic and cardiovascular diseases. Physiological estrogen signaling is anti-inflammatory with vascular protective effects, but pharmacological replacement use in transgender and postmenopausal individuals is associated with thrombosis and other side effects. Crucially, the loss of this important sex hormone following menopause or with gender reassignment is associated with worsened pro-inflammatory states linked to increased oxidative stress, myocardial fibrosis, and, ultimately, diastolic dysfunction, also known as Yentl syndrome. While there is a growing body of knowledge on distinctive purinergic or estrogen signaling and endothelial health, much less is known about the relationships between the two signaling pathways. Continued studies of the interactions between these pathways will allow further insight into future therapeutic targets to improve the cardiovascular health of aging women without imparting deleterious side effects.

INTRODUCTION: Stricturing Crohn's disease is a common phenotype and treatment aims to improve symptoms, prevent complications, assess for proximal bowel disease activity, and screen for upstream neoplasm. Management is challenging due to diagnostic limitations, stricture composition, and recurrence rate.

AREAS COVERED: Categorizing a stricture as inflammatory or fibrotic is necessary to determine appropriate management. Inflammatory strictures are treated with medical therapy, and fibrostenotic strictures require endoscopic or surgical management. While EBD is increasingly utilized, stricture recurrence rates remain high, necessitating repeat endoscopic procedures or surgery. We performed a PubMed (MEDLINE database) search for the latest research on IBD-related stricture management, including detection, diagnosis, and medical and procedural therapies. We highlight the current literature on endoscopic techniques for the treatment of intestinal strictures and future areas of research.

EXPERT OPINION: The field of intestinal stricture management is expected to evolve in the coming years and will include enhanced imaging modalities, medication optimization, and increasing use of advanced endoscopic techniques.

Therapeutic drug monitoring (TDM) for dose modification of biologics has the potential to improve patient outcomes. The US Food and Drug Administration (FDA) and the American Association of Pharmaceutical Scientists (AAPS) hosted the first US-based public workshop on TDM of biologics with contributions from a broad array of interested parties including healthcare providers, clinical pharmacologists, test developers, bioanalysis and immunogenicity scientists, health economics and outcomes research (HEOR) experts and regulators. The key insight was that despite a body of evidence to support TDM in certain therapeutic areas, there remain substantial challenges to widespread clinical implementation. There is a lack of consensus regarding the integration of TDM in clinical guidelines, and a lack of consensus on the cost-effectiveness of TDM; both factors contribute to the difficulty that healthcare providers face in obtaining reimbursement for TDM (both coverage of testing itself, and coverage of potential dosing modifications). The HEOR experts outlined alternative routes to obtaining reimbursement and suggested advocating for changes in coverage policies to promote TDM use in the clinic. Reaching alignment across policy makers, patients and advocacy groups, payers, and healthcare providers, on specific treatment settings where TDM will be clearly beneficial, was identified as an important step to advancing TDM implementation for the benefit of patients.