Cancer Risk in Patients Treated with the JAK Inhibitor Tofacitinib: Systematic Review and Meta-Analysis.

Tofacitinib is approved for several immune-mediated inflammatory diseases, but safety concerns have recently been raised. We searched PubMed (accessed on 27 February 2023) for original articles regarding tofacitinib's cancer risk when used for rheumatoid arthritis, ulcerative colitis, Crohn's disease, psoriatic arthritis, and ankylosing spondylitis. Of the 2047 initial records, 22 articles describing 26 controlled studies (including 22 randomized controlled trials) were selected. In the comparison between tofacitinib and any control treatment, the relative risk (RR) for any cancer was 1.06 (95% CI, 0.86-1.31; p = 0.95). In separate comparisons between tofacitinib and either a placebo or biological therapy, no difference was found in the overall cancer risk (vs. placebo, RR = 1.04; 95% CI, 0.44-2.48; p = 0.95; vs. biological drugs, RR = 1.06; 95% CI, 0.86-1.31; p = 0.58). When tofacitinib was compared to tumor necrosis factor (TNF) inhibitors, the overall cancer RR was 1.40 (95% CI, 1.06-2.08; p = 0.02). Similarly, significant results were obtained for all cancers, except for non-melanoma skin cancer (RR = 1.47; 95% CI, 1.05-2.06; p = 0.03), and for this skin cancer alone (RR = 1.30; 95% CI, 0.22-5.83; p = 0.88). In conclusion, no difference in the overall cancer risk was found between tofacitinib and either a placebo or biological drugs, while a slightly higher risk was found in patients treated with tofacitinib than anti-TNF agents. Further studies are needed to better define the cancer risk of tofacitinib therapy.

Periodontitis prevalence and severity in inflammatory bowel disease: A case-control study.

BACKGROUND: Recent evidence is supporting the notion of a microbiological and immunological continuum on the gum-gut axis in health and disease. Therefore, the purpose of this study was to assess the prevalence and risk indicators of periodontitis in patients with Crohn's disease (CD) or ulcerative colitis (UC) compared to age- and sex-matched controls without inflammatory bowel disease (IBD). METHODS: A total of 180 IBD (117 CD, 60 UC, 3 IBD-unclassified) and 180 healthy controls were compared for their periodontitis diagnosis (Centers for Disease Control and Prevention/American Academy of Periodontology [CDC/AAP] case definition) and full-mouth periodontal parameters. In addition, explorative logistic regression models were performed. RESULTS: Significantly more patients with IBD had moderate/severe periodontitis (85.6% vs. 65.6%, p < 0.001) and severe periodontitis (36.7% vs. 25.6%, p < 0.001) than controls. Differences were higher in the 35-50 and 51-65 age groups, without significant changes between CD and UC. IBD subjects presented chances ∼3.5 higher of having moderate/severe periodontitis (p < 0.001). Significant variables associated with periodontitis in the whole sample were older age, presence of IBD, and higher full-mouth plaque scores, whereas in the IBD group they were male sex, IBD-associated surgery, and IBD duration and localization (pancolitis). Positive risk indicators for IBD were periodontitis severity and higher bleeding scores, while smoking was negatively associated with UC. CONCLUSIONS: Relevant associations between IBD and periodontitis were found, being modified by CD and UC clinical characteristics. Preventive and therapeutic strategies involving the gum-gut axis should be enforced in IBD patients.

Inflammatory bowel disease and immune-mediated inflammatory diseases: looking at the less frequent associations.

Patients with inflammatory bowel disease (IBD) often have other immune-mediated inflammatory diseases (IMIDs), and the prevalence of any IMID is higher in IBD patients than in the general population. IBD and other IMIDs involve alterations in innate and adaptive immune responses. Their co-occurrence depends on shared immune and inflammatory processes, pathogenic mechanisms, and genetic and environmental risk factors, including drugs, especially tumor necrosis factor inhibitors. The more common IMIDs associated with IBD have been widely described, so this review focuses on the less frequent associations. The IMIDs discussed here are skin disorders (psoriasis, atopic dermatitis, vitiligo, epidermolysis bullosa acquisita, cutaneous polyarteritis nodosa, and hidradenitis suppurativa), hepato-pancreatic diseases (autoimmune hepatitis, granulomatous hepatitis, and autoimmune pancreatitis), endocrine diseases (autoimmune thyroid diseases, and type 1 diabetes mellitus), multiple sclerosis, and respiratory diseases (asthma, bronchiectasis, and interstitial pneumonia). The early detection of IMIDs in IBD patients is important to prevent their deleterious clinical course and limit their psychological impact. Care for IBD patients with IMIDs should be multispecialist, with a single therapeutic strategy instead of treating each disease separately.

Crosstalk between Irisin Levels, Liver Fibrogenesis and Liver Damage in Non-Obese, Non-Diabetic Individuals with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Insulin resistance plays a relevant role in the onset of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH) and fibrosis. Irisin is an exercise-induced myokine involved in the regulation of energy homeostasis and glucose metabolism. Additionally, pre-clinical models have shown a potential role of irisin in the pathogenesis of NAFLD. The aim of this study is to explore the association between irisin, histological features and biomarkers of liver fibrogenesis in non-diabetic, non-obese, biopsy-proven NAFLD individuals. METHODS: Forty-one patients with histological evidence of NAFLD were included. Circulating irisin and direct markers of fibrogenesis N-terminal type III collagen propeptide (PRO-C3) and type VI collagen cleavage product (PRO-C6) were measured by ELISA. RESULTS: Median age of the cohort was 45 years (41-51) and 80.4% were male. Significant fibrosis (stage ≥ 2) was present in 36.6% of cases. Circulating irisin, PRO-C3 and PRO-C6 levels were significantly higher in subjects with fibrosis stage ≥ 2 when compared to those with fibrosis stage < 2 (5.96 ng/mL (95% CI = 4.42-9.19) vs. 2.42 ng/mL (95% CI = 1.73-5.95), p = 0.033; 9.5 ng/mL (95% CI = 7.7-13.6) vs. 6.2 ng/mL (95% CI = 4.9-8.9), p = 0.016; 6.6 ng/mL (95% CI = 5.6-7.9) vs. 5.1 ng/mL (95% CI = 4.2-5.4), p = 0.013, respectively). Irisin levels were similarly distributed between the features of NASH. Circulating irisin positively correlated with both PRO-C3 and PRO-C6 levels (r = 0.47, p = 0.008 and r = 0.46, p = 0.002). CONCLUSIONS: Increased circulating irisin levels may identify a more aggressive phenotype of liver disease with increased fibrogenesis and more severe liver damage.

Insights into the role of gastrointestinal ultrasound in ulcerative colitis.

Endoscopic evaluation with histological sampling is the gold standard for the diagnosis and follow-up of patients with inflammatory bowel disease (IBD), but in the past few years, gastrointestinal ultrasound (GIUS) has been gaining ground. Due to the transmural nature of inflammation in Crohn's disease, GIUS has been mainly applied in this context. However, GIUS is now being reported to be accurate also for ulcerative colitis (UC). This review summarizes current knowledge on the use of GIUS in UC, with a focus on clinical practice. The review covers topics such as GIUS parameters, especially bowel wall thickness; the use of GIUS in assessing disease extent and in monitoring disease activity; GIUS indexes and scores; and the combination of GIUS with transperineal ultrasound for a better assessment of the rectum. With the always growing body of evidence supporting the accuracy of GIUS in UC, this diagnostic imaging modality can be expected to play a bigger role in disease flare evaluation, early treatment monitoring, and acute severe disease management.

Risk Factors of Urothelial Cancer in Inflammatory Bowel Disease.

Extraintestinal cancers are important complications in patients with inflammatory bowel disease (IBD). A limited number of publications are available regarding the association between IBD and urothelial cancer. The primary outcome of our study was the comparison of the prevalence of urothelial cancer in patients with IBD with respect to the prevalence in the general population. Secondary outcomes were the assessment of risk factors for the onset of urothelial cancer in IBD. In a retrospective study we examined the medical records of all patients with a confirmed diagnosis of IBD followed in our clinic between 1978 and 2021. For each of the patients with identified urothelial cancer, more than ten patients without cancer were analyzed. Furthermore, 5739 patients with IBD were analyzed and 24 patients diagnosed with urothelial cancer were identified. The incidence of urothelial cancer, compared with the incidence in the general population, was not significantly different (0.42% vs. 0.42%; p = 0.98). Twenty-three cases were then compared (1 case was discarded due to lack of follow-up data) against 250 controls. During the multivariate analysis, smoking (odds ratio, OR = 8.15; 95% confidence interval, CI = 1.76-37.63; p = 0.007) and male sex (OR = 4.04; 95% CI = 1.29-12.66; p = 0.016) were found as risk factors. In conclusion, patients with IBD have a similar risk of developing urothelial cancer compared to the general population, but males with a history of smoking are at increased risk.

Artificial intelligence in gastrointestinal endoscopy for inflammatory bowel disease: a systematic review and new horizons.

INTRODUCTION: Since the advent of artificial intelligence (AI) in clinical studies, luminal gastrointestinal endoscopy has made great progress, especially in the detection and characterization of neoplastic and preneoplastic lesions. Several studies have recently shown the potential of AI-driven endoscopy for the investigation of inflammatory bowel disease (IBD). This systematic review provides an overview of the current position and future potential of AI in IBD endoscopy. METHODS: A systematic search was carried out in PubMed and Scopus up to 2 December 2020 using the following search terms: artificial intelligence, machine learning, computer-aided, inflammatory bowel disease, ulcerative colitis (UC), Crohn's disease (CD). All studies on human digestive endoscopy were included. A qualitative analysis and a narrative description were performed for each selected record according to the Joanna Briggs Institute methodologies and the PRISMA statement. RESULTS: Of 398 identified records, 18 were ultimately included. Two-thirds of these (12/18) were published in 2020 and most were cross-sectional studies (15/18). No relevant bias at the study level was reported, although the risk of publication bias across studies cannot be ruled out at this early stage. Eleven records dealt with UC, five with CD and two with both. Most of the AI systems involved convolutional neural network, random forest and deep neural network architecture. Most studies focused on capsule endoscopy readings in CD (n = 5) and on the AI-assisted assessment of mucosal activity in UC (n = 10) for automated endoscopic scoring or real-time prediction of histological disease. DISCUSSION: AI-assisted endoscopy in IBD is a rapidly evolving research field with promising technical results and additional benefits when tested in an experimental clinical scenario. External validation studies being conducted in large and prospective cohorts in real-life clinical scenarios will help confirm the added value of AI in assessing UC mucosal activity and in CD capsule reading. PLAIN LANGUAGE SUMMARY: Artificial intelligence for inflammatory bowel disease endoscopy Artificial intelligence (AI) is a promising technology in many areas of medicine. In recent years, AI-assisted endoscopy has been introduced into several research fields, including inflammatory bowel disease (IBD) endoscopy, with promising applications that have the potential to revolutionize clinical practice and gastrointestinal endoscopy.We have performed the first systematic review of AI and its application in the field of IBD and endoscopy.A formal process of paper selection and analysis resulted in the assessment of 18 records. Most of these (12/18) were published in 2020 and were cross-sectional studies (15/18). No relevant biases were reported. All studies showed positive results concerning the novel technology evaluated, so the risk of publication bias cannot be ruled out at this early stage.Eleven records dealt with UC, five with CD and two with both. Most studies focused on capsule endoscopy reading in CD patients (n = 5) and on AI-assisted assessment of mucosal activity in UC patients (n = 10) for automated endoscopic scoring and real-time prediction of histological disease.We found that AI-assisted endoscopy in IBD is a rapidly growing research field. All studies indicated promising technical results. When tested in an experimental clinical scenario, AI-assisted endoscopy showed it could potentially improve the management of patients with IBD.Confirmatory evidence from real-life clinical scenarios should be obtained to verify the added value of AI-assisted IBD endoscopy in assessing UC mucosal activity and in CD capsule reading.

Effectiveness and safety of switching to adalimumab biosimilar ABP 501 in Crohn's disease: the extrapolation concept.

We sincerely thank Viscido et al. for their appropriate and sharable comments on our recent study on adalimumab biosimilar ABP 501 in Crohn's disease (CD). The use of a biosimilar in inflammatory disorders is one of the current main topics, given the great opportunity to save resources that can be invested in innovative drugs and the ethical problems that non-medical switching can generate.

Role of Compositum Zeolite® in management of inflammatory bowel disease: a pilot study.

BACKGROUND: Zeolites are crystalline mineral aluminosilicate compounds with microporous structures of tetrahedrons and huge porosity. In the gut, these silicates act as adsorbents, ion-exchangers, catalysts, detergents or antidiarrheic agents. In addition to its well-known antioxidant effect, a new potential advantage of Zeolite could be the microbiome modulation. In this scenery, we aimed to investigate the effect of this compound on inflammation among inflammatory bowel disease patients, assessing both clinical activity and inflammatory markers. METHODS: This was an open one branch pilot study involving 20 IBD patients, both affected with Crohn's disease and ulcerative colitis affering to San Giovanni Antica Sede Hospital, Città della Salute e della Scienza in Turin. Each patient was given Compositum Zeolite® 6 g/die for 56 days; follow-up time was 60 days from the end of Zeolite therapy. Primary outcomes of the study were to evaluate the improvement of the quality of life (Partial Mayo score or Harvey Bradshaw Index) and the compliance to therapy, while secondary outcome was the reduction of calprotectin value. RESULTS: Of the twenty patients enrolled, 4 did not attend the scheduled check-up visit and 2 reported non-adherence to the therapy with Compositum Zeolite® so these 6 patients were considered as drop out and their data were not included in statistical analysis. So, compliance rate was 70%, that is similar to general adherence to therapy in our setting. Regarding Ulcerative Colitis patients, at the moment of enrolment mean Mayo Partial Score (MPS) was 3.09 (CI: 1.76-4.41) while after 8 weeks of Compositum Zeolite® supplementation the mean MPS was 2.72 (CI: 1.45-4.00) (P=0.57) and after 60 days of follow-up mean MPS was 1.9 (CI: 0.85-2.97) (P=0.24). As Crohn's disease patients are concerned, HBI Score at enrolment was 5.3 (CI: 3.38-7.29) while mean score after 8 week of therapy was 4 (CI: 2.85-5.15) (P=0.042) and after 60 days of follow-up mean score was 3.1 (CI: 1.48-4.87) (P=0.18). Mean calprotectin value at enrolment was 925.64 (CI: 451.83-1399.45). while after 2 months of Compositum Zeolite® addon therapy was 952.72 (CI: 492.73-1412.73); P value 0.93. After 2 months of follow-up mean value was 724.45 (CI: 240.15-1208.73) P value 0.3. CONCLUSIONS: Compositum Zeolite® has a compliance rate similar to the other prescribed therapies and is a good addon therapy to improve activity indexes, mainly in Crohn's disease. It also seems to improve inflammatory indexes, even if maybe dose or time of therapy were insufficient to reach a full negativization of these parameters.

Pitfalls in the Diagnosis of Coeliac Disease and Gluten-Related Disorders.

The spectrum of gluten-related disorders (GRD) has emerged as a relevant phenomenon possibly impacting on health care procedures and costs worldwide. Current classification of GRD is mainly based on their pathophysiology, and the following categories can be distinguished: immune-mediated disorders that include coeliac disease (CD), dermatitis herpetiformis (DH), and gluten ataxia (GA); allergic reactions such as wheat allergy (WA); and non-coeliac gluten sensitivity (NCGS), a condition characterized by both gastrointestinal and extra-intestinal symptoms subjectively believed to be induced by the ingestion of gluten/wheat that has recently gained popularity. Although CD, DH, and WA are well-defined clinical entities, whose diagnosis is based on specific diagnostic criteria, a diagnosis of NCGS may on the contrary be considered only after the exclusion of other organic disorders. Neither allergic nor autoimmune mechanisms have been found to be involved in NCGS. Mistakes in the diagnosis of GRD are still a relevant clinical problem that may result in overtreatment of patients being unnecessary started on a gluten-free diet and waste of health-care resources. On the basis of our clinical experience and literature, we aim to identify the main pitfalls in the diagnosis of CD and its complications, DH, and WA. We provide a practical methodological approach to guide clinicians on how to recognize and avoid them.

Preventing Infections by Encapsulated Bacteria Through Vaccine Prophylaxis in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), which comprises ulcerative colitis and Crohn's disease, is an immune-mediated, chronic-relapsing, disabling disorder which is associated with increased mortality and poor patients' quality of life. Patients with IBD are at increased risk of infections for many reasons. In fact, IBD often requires a lifelong immunosuppressive and/or biologic therapy, both commonly associated with respiratory and opportunistic infections, but also gastrointestinal, urinary tract infections, and sepsis. Moreover, impaired spleen function has been found in a considerable proportion of IBD patients, further increasing the risk of developing infections sustained by encapsulated bacteria, such as S. pneumoniae, H. influenzae, and N. meningitidis. Finally, comorbidities and surgery represent additional risk factors for these patients. Despite the availability of vaccinations against the most common serotypes of encapsulated bacteria, uncertainties still exist regarding a proper vaccination strategy and the actual effectiveness of vaccinations in this particular setting. Aim of this narrative review is to focus on the broad topic of vaccinations against encapsulated bacteria in IBD patients, discussing the clinical impact of infections, predisposing factors, vaccinations strategies, and unmet research and clinical needs.

Effectiveness and safety of adalimumab biosimilar ABP 501 in Crohn's disease: an observational study.

BACKGROUND AND OBJECTIVE: there are no studies in the literature about the effectiveness of adalimumab biosimilar ABP 501 in Crohn's disease. The aim of this study was to evaluate its effectiveness and safety. METHODS: an observational study was performed in Crohn's disease patients treated with ABP 501, with the classic induction and maintenance regimen and in Crohn's disease patients who were switched from the adalimumab originator to ABP 501. RESULTS: eighty-seven patients were included in the study, of which 25 were naïve to the adalimumab originator and 62 were switched to ABP 501. In adalimumab-naïve patients, clinical response at three months was 60% (15/25) and clinical remission at three months was 56% (14/25). At six months, 95.2% (59/62) of the patients switched to ABP 501 were still in therapy, without a significant increase of clinical activity (Harvey-Bradshaw index from 3.4, 95% CI = 2.4-4.4, to 3.8, 95% CI = 2.7-4.9, p = 0.23) and inflammatory biomarkers (C-reactive protein from 4.2 mg/l, 95% CI = 2.5-5.9 mg/l, to 3.6 mg/l, 95% CI = 2.2-5 mg/l, p = 0.32). There were no unexpected adverse events during the study period. CONCLUSIONS: our results support ABP 501 as an effective and well-tolerated drug, with a good interchangeability with its originator for the treatment of Crohn's disease.

Adalimumab versus azathioprine to halt the progression of bowel damage in Crohn's disease: application of Lémann Index.

Background: The Lémann Index (LI) was recently developed to evaluate the cumulative bowel damage in patients with Crohn's disease (CD).Aims: To search for a difference between adalimumab and azathioprine to halt the progression of bowel damage in active CD, using the LI.Methods: A single-centre, retrospective study was conducted. Patients with CD were included if they had colonoscopy and magnetic resonance enterography performed within 4 months from the start of adalimumab or azathioprine and repeated after 12 months of therapy. Primary outcome was reached if the increase of LI after 12 months of treatment was <0.3, the drug was not stopped, and the use of systemic steroids was continued for no more than 3 months.Results: Ninety-one patients were enrolled, 31 (34.1%) of them treated with adalimumab and 60 (65.9%) with azathioprine. Sixty-seven percent of patients treated with adalimumab reached the primary outcome compared to 28.3% of patients treated with azathioprine (p = .0006). The LI in the group on adalimumab therapy decreased after 12 months (from 9.9 to 8.8), while in the group on azathioprine therapy it increased (from 7.7 to 8.8).Conclusion: Treatment with adalimumab halts the progression of bowel damage in CD while that with azathioprine does not.

Dual biological therapy with anti-TNF, vedolizumab or ustekinumab in inflammatory bowel disease: a systematic review with pool analysis.

Background: Inflammatory bowel diseases patients eligible for biological therapy represent a group with considerable disease burden and biologics only achieve 40% clinical remission rates in responders after 1 year of therapy. Aims: To collect all the published data about patients treated with dual biological therapy with an Anti-TNF, vedolizumab or ustekinumab, for a period of at least 3 months and to pool the data about the effectiveness and safety. Methods: A MEDLINE, and Web of Science search of all studies published in English until 1 January 2019 was conducted. Results: We included 7 studies with a total of 18 patients. Fifteen patients were treated with a combination of an anti-TNF and vedolizumab, 3 patients were treated with vedolizumab and ustekinumab. Fifty-six percent of patients were affected by Crohn's disease and 50% of patients were treated with an immunosuppressant drug or steroid too. A clinical improvement was obtained in 100% of patients, and an endoscopic improvement in 93% of patients. No serious adverse events were reported. Conclusions: The use of dual biological therapy is an attractive therapeutic option and may be an opportunity to better tailor and personalize the therapies for patients. Further studies, as randomized control trials, to provide comparative efficacy and safety endpoints of combination therapies, and to clarify potential advantages of combined biological therapies, are needed.

Oral iron supplementation with Feralgine® in inflammatory bowel disease: a retrospective observational study.

BACKGROUND: Inflammatory bowel disease (IBD) is a relapsing chronic disease of the gastrointestinal (GI) tract. Among IBD patients, anemia is more frequent than in general population. Recent studies demonstrated a good iron absorption using Feralgine®, a compound of ferrous bysglicinate chelate and alginic acid, oral supplementation with both good compliance rate and efficacy in treating iron deficiency anemia especially due to its high oral bioavailability. In this study we evaluated hemoglobin (Hb) improvement after Feralgine® supplementation in patients with IBD and anemia. METHODS: This is a retrospective observational study. All data were derived from the patients' registry of the Inflammatory Bowel Disease Center, San Giovanni Antica Sede-Molinette Hospital, Turin, Italy. All IBD patients suffering from anemia and treated with Feralgine® (Tecnofer Plus), 1 capsule daily, were selected. RESULTS: Mean Hb value increased from 11 g/dL (95% confidence interval [CI]: 10.72-11.47) to 12.2 g/dL (95% CI: 11.6-12.52, P=0.0001), after three months of Feralgine® supplementation. While 90% of the patients did not report adverse events, 10% experienced dyspepsia and worsening of diarrhea. Only 6% of patients suspended oral iron supplementation due to GI intolerance (adherence rate 94%). CONCLUSIONS: Oral supplementation with Feralgine® induced a significant improvement in Hb levels, suggesting that in IBD patients with mild or moderate anemia, oral iron supplementation could be considered the first line therapy. We suggest further studies on larger cohorts to assess iron, ferritin and transferrin saturation improvement after this treatment.