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Summary: Background: The Bowel Ultrasound Score (BUSS) accurately detects therapy-related changes by using the Simple Endoscopic Score for Crohn's disease (SES-CD) as the reference standard. We aimed to evaluate ultrasound remission as a treatment target and its prediction for long-term endoscopic remission. Methods: This single-centre prospective observational study, based at a tertiary referral centre in Milan, Italy, enrolled, between March 1, 2018, and January 31, 2021, adult patients with active CD (SES-CD >2) who were starting biologics. Colonoscopy and IUS was performed at baseline and at 12 months (mean 12.8 ± 4.2). The primary outcome was the predictive value of ultrasound remission at week 12 (BUSS ≤3.52) for long-term endoscopic remission at 12 months. The International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) was also calculated and optimal cut-point to detect endoscopic remission was identified through ROC analysis. Findings: 93 patients with CD were included. Of these, 22 patients (24%) achieved endoscopic remission. Week 12 ultrasound remission predicted endoscopic remission (59% compared with 41% of the patients who were not in ultrasound remission; OR 9.93, 95% CI 3.10–31.80; p

Background: The dysregulation of the gut-brain axis in chronic inflammatory bowel diseases can cause neuro-psychological disturbances, but the underlying mechanisms are still not fully understood. The choroid plexus (CP) maintains brain homeostasis and nourishment through the secretion and clearance of cerebrospinal fluid. Recent research has demonstrated the existence of a CP vascular barrier in mice which is modulated during intestinal inflammation.This study investigates possible correlations between CP modifications and inflammatory activity in patients with Crohn's disease (CD). Methods: In this prospective study, 17 patients with CD underwent concomitant abdominal and brain 3 T MRI. The volume and permeability of CP were compared with levels of C-reactive protein (CRP), fecal calprotectin (FC), sMARIA and SES-CD scores. Results: The CP volume was negatively correlated with CRP levels (R = -0.643, p-value = 0.024) and FC (R = -0.571, p-value = 0.050). DCE metrics normalized by CP volume were positively correlated with CRP (K-trans: R = 0.587, p-value = 0.045; Vp: R = 0.706, p-value = 0.010; T1: R = 0.699, p-value = 0.011), and FC (Vp: R = 0.606, p-value = 0.037). Conclusions: Inflammatory activity in patients with CD is associated with changes in CP volume and permeability, thus supporting the hypothesis that intestinal inflammation could affect the brain through the modulation of CP vascular barrier also in humans.

Background: Vedolizumab (VDZ) and infliximab are used to treat moderate to severe ulcerative colitis (UC). The choice of the drug to use at first-line is often based on a combination of clinical and economic factors. The cost of treatment pathway is rarely considered. Therefore, this cost-consequence analysis (CCA) investigated the overall costs of treatment pathway for vedolizumab followed by infliximab (VDZ → IFX) compared to infliximab followed by vedolizumab (IFX → VDZ). Methods: We used a published cost-consequence model (CCM), based on a targeted literature search reporting the time-on-treatment data for vedolizumab or infliximab in UC in first and second-line of treatment. CCM time horizon was defined by the length of treatment sequences. Considering the Italian hospital perspective, the CCA evaluated the biologic drugs acquisition costs, drug administration costs, hospitalization costs, switch costs, colectomy costs and third-line treatment costs. Third-line options included colectomy, tofacitinib, ustekinumab or dose escalation of second-line biologic. Results: Over the 5.2-year time horizon (duration of the longer VDZ → IFX pathway), the mean cost per patient of VDZ → IFX pathway was slightly lower than the mean cost per patient of IFX → VDZ pathway (€ 86,339 vs 89,636). The CCM predicted that using VDZ as first-line treatment delayed the time to costly third-line therapies compared to first-line using IFX (VDZ-first-line median time-on-treatment 3.6-years and IFX-second-line 1.6-years; IFX-first-line 1.4-years and VDZ-second-line 2.3-years and third-line 1.5-years). Conclusion: The CCA showed that a biologic treatment pathway that begins with first-line vedolizumab is not more expensive than one beginning with first-line infliximab and delayed the time to costly third-line.

Gut microbiota dysbiosis has a critical role in the pathogenesis of inflammatory bowel diseases, prompting the exploration of novel therapeutic approaches like fecal microbiota transplantation, which involves the transfer of fecal microbiota from a healthy donor to a recipient with the aim of restoring a balanced microbial community and attenuating inflammation. Fecal microbiota transplantation may exert beneficial effects in inflammatory bowel disease through modulation of immune responses, restoration of mucosal barrier integrity, and alteration of microbial metabolites. It could alter disease course and prevent flares, although long-term durability and safety data are lacking. This review provides a summary of current evidence on fecal microbiota transplantation in inflammatory bowel disease management, focusing on its challenges, such as variability in donor selection criteria, standardization of transplant protocols, and long-term outcomes post-transplantation.

Abstract Background In Italy, the incidence of SARS-CoV-2 infection peaked in April and November 2020, defining two pandemic waves of coronavirus disease 2019 (COVID-19). This study compared the characteristics and outcomes of patients with inflammatory bowel disease (IBD) and SARS-CoV-2 infections between pandemic waves. Methods Observational longitudinal study of IBD patients with SARS-CoV-2 infection. Patients with established diagnoses of IBD and of SARS-CoV-2 infection were consecutively enrolled in two periods: (i) first wave, from 1 March 2020 to 31 May 2020; and (ii) second wave, from 15 September to 15 December 2020. Results We enrolled 937 IBD patients (219 in the first wave, 718 in the second wave). Patients of the first wave were older (mean ± SD: 46.3 ± 16.2 vs. 44.1 ± 15.4 years, p = 0.06), more likely to have ulcerative colitis (58.0% vs. 44.4%, p

Background & Aims: DNA methylation alterations may provide important insights into gene-environment interaction in cancer, aging, and complex diseases, such as inflammatory bowel disease (IBD). We aim first to determine whether the circulating DNA methylome in patients requiring surgery may predict Crohn’s disease (CD) recurrence following intestinal resection; and second to compare the circulating methylome seen in patients with established CD with that we had reported in a series of inception cohorts. Methods: TOPPIC was a placebo-controlled, randomized controlled trial of 6-mercaptopurine at 29 UK centers in patients with CD undergoing ileocolic resection between 2008 and 2012. Genomic DNA was extracted from whole blood samples from 229 of the 240 patients taken before intestinal surgery and analyzed using 450KHumanMethylation and Infinium Omni Express Exome arrays (Illumina, San Diego, CA). Coprimary objectives were to determine whether methylation alterations may predict clinical disease recurrence; and to assess whether the epigenetic alterations previously reported in newly diagnosed IBD were present in the patients with CD recruited into the TOPPIC study. Differential methylation and variance analysis was performed comparing patients with and without clinical evidence of recurrence. Secondary analyses included investigation of methylation associations with smoking, genotype (MeQTLs), and chronologic age. Validation of our previously published case-control observation of the methylome was performed using historical control data (CD, n = 123; Control, n = 198). Results: CD recurrence in patients following surgery is associated with 5 differentially methylated positions (Holm P < .05), including probes mapping to WHSC1 (P = 4.1 × 10-9, Holm P = .002) and EFNA3 (P = 4.9 × 10-8, Holm P = .02). Five differentially variable positions are demonstrated in the group of patients with evidence of disease recurrence including a probe mapping to MAD1L1 (P = 6.4 × 10-5). DNA methylation clock analyses demonstrated significant age acceleration in CD compared with control subjects (GrimAge + 2 years; 95% confidence interval, 1.2–2.7 years), with some evidence for accelerated aging in patients with CD with disease recurrence following surgery (GrimAge +1.04 years; 95% confidence interval, -0.04 to 2.22). Significant methylation differences between CD cases and control subjects were seen by comparing this cohort in conjunction with previously published control data, including validation of our previously described differentially methylated positions (RPS6KA2 P = 1.2 × 10-19, SBNO2 = 1.2 × 10-11) and regions (TXK [false discovery rate, P = 3.6 × 10-14], WRAP73 [false discovery rate, P = 1.9 × 10-9], VMP1 [false discovery rate, P = 1.7 × 10-7], and ITGB2 [false discovery rate, P = 1.4 × 10-7]). Conclusions: We demonstrate differential methylation and differentially variable methylation in patients developing clinical recurrence within 3 years of surgery. Moreover, we report replication of the CD-associated methylome, previously characterized only in adult and pediatric inception cohorts, in patients with medically refractory disease needing surgery.

Background: Iron deficiency anemia (IDA) is a common extraintestinal manifestation of inflammatory bowel disease (IBD), affecting around one-third of patients. Objective: To compare IBD progression and healthcare resource utilization in patients with and without a co-diagnosis of IDA in a real-world setting. Design: A retrospective comparative study was conducted using Italian entities’ administrative databases, covering 9.3 million health-assisted individuals. Methods: Adult IBD patients diagnosed with ulcerative colitis and/or Crohn’s disease were enrolled between January 2010 and September 2017. Within 12 months from IBD diagnosis, IDA was identified by at least one prescription for iron and/or IDA hospitalization and/or blood transfusion (proxy of diagnosis). IBD population was divided according to the presence/absence of IDA. Given the nonrandom patients’ allocation, propensity score matching (PSM) was applied to abate potential unbalances between the groups. Before and after PSM, IBD progression (in terms of IBD-related hospitalizations and surgeries), and healthcare resource costs were assessed. Results: Overall, 13,475 IBD patients were included, with an average age at diagnosis of 49.9 years, and a 53.9% percentage of male gender. Before PSM, 1753 (13%) patients were IBD–IDA, and 11,722 (87%) were IBD–non-IDA. Post-PSM, 1753 IBD–IDA patients were matched with 3506 IBD–non-IDA. Before PSM, IBD progression was significantly higher in IBD–IDA (12.8%) than in IBD–non-IDA (6.5%) ( p

Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring ad hoc interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice.

Delayed diagnosis is a challenge in the management of inflammatory bowel disease (IBD). Several studies show a significant association between diagnostic delay and disease progression to complications and surgery, especially in Crohn’s disease (CD). What risk factors are associated with diagnostic delay in IBD remains unclear. In order to reduce diagnostic delay, the Red Flags Index has been developed and validated. The combination of the Red Flags Index score and non-invasive biomarkers such as fecal calprotectin seems to be highly accurate in screening patients with underlying IBD to be referred for further diagnostic workup and eventual early effective treatment strategies. Our literature review aims to obtain a comprehensive overview of the impacts of diagnostic delay in IBD on the potential risk factors associated with IBD, how diagnostic tools may be effective in reducing diagnostic delay, and future perspectives in this field.

Abstract Data regarding double switching from originator infliximab (IFX) to IFX biosimilars in inflammatory bowel diseases (IBDs) are lacking. The purpose of this study was to evaluate the safety and efficacy of switching from originator IFX to CT‐P13 and subsequently to SB2 (double switch) in patients with IBD. Patients undergoing IFX‐double switch in eight Centers in Lombardy (Italy) from November 2018 to May 2019 were retrospectively analyzed. The IFX discontinuation rate, incidence and type of adverse events (AEs), and clinical remission rate were recorded. A comparison with a control group of patients with IBD single‐switched from originator IFX to CT‐P13 was performed, before and after an inverse probability of treatment weighting (IPTW)‐based propensity score analysis. Fifty‐two double‐switched patients with IBD were enrolled. The 24‐ and 52‐week proportions of patients continuing on IFX therapy following the second switch (CTP13 → SB2) were 98% (95% confidence interval [CI] 94%–100%) and 90% (95% CI 81%–99%), respectively. Four patients experienced a total of five AEs, all graded 1–3 according to Common Terminology Criteria for Adverse Events (CTCAE). No infusion reactions were observed. The 24‐week and follow‐up end clinical remission rates following the second switch were 94% and 88%, respectively. No differences were observed in the safety and efficacy outcomes by comparing the double‐switch group with a single‐switch group of 66 patients with IBD; all these results were confirmed by IPTW‐adjusted analysis. The study suggests both the safety and efficacy of the double switch from originator IFX to CT‐P13 and SB2 in patients with IBD is maintained. This strategy may be associated with potential cost implications.

Abstract Background Ulcerative colitis (UC) is an inflammatory bowel disease with increasing prevalence worldwide. Current treatment strategies place considerable economic and humanistic burdens on patients. The aim of this study was to determine the socioeconomic burden of UC in adult patients in European countries in a real-world setting. Methods In this retrospective, cross-sectional and observational pan-European study, patients with moderate or severe UC were assigned to ARM 1 and patients who had moderate or severe UC but achieved mild or remission status 12 months before index date (or clinical consultation date), were assigned to ARM 2. Clinical and medical resource use data were collected via electronic case report forms, and data on non-medical and indirect costs, and health-related quality of life (HRQoL) were collected via patient and public involvement and engagement (PPIE) questionnaires. Per-patient annual total costs per ARM and per country were calculated using the collated resource use in the last 12 months (between the start of the documentation period and patient consultation or index date) and country specific unit costs. Quality of life was described by arm and by country. Results In the physician-reported eCRF population (n = 2966), the mean annual direct medical cost was €4065 in ARM 1 (n = 1835) and €2935 in ARM 2 (n = 1131). In the PPIE population (ARM 1, n = 1001; ARM 2, n = 647), mean annual direct cost was €4526 in ARM 1 and €3057 in ARM 2, mean annual direct non-medical cost was €1162 in ARM 1 and €1002 in ARM 2, mean annual indirect cost was €3098 in ARM 1 and €2309 ARM 2, and mean annual total cost was in €8787 in ARM 1 and €6368 in ARM 2. HRQoL scores showed moderate to high burden of UC in both groups. Conclusions The cost and HRQoL burden were high in patients in both ARM 1 and ARM 2 indicating unmet needs in the UC active population.

Immune mediated inflammatory diseases (IMIDs) are a heterogeneous group of debilitating, multifactorial and unrelated conditions featured by a dysregulated immune response leading to destructive chronic inflammation. The immune dysregulation can affect various organ systems: gut (e.g., inflammatory bowel disease), joints (e.g., rheumatoid arthritis), skin (e.g., psoriasis, atopic dermatitis), resulting in significant morbidity, reduced quality of life, increased risk for comorbidities, and premature death. As there are no reliable disease progression and therapy response biomarkers currently available, it is very hard to predict how the disease will develop and which treatments will be effective in a given patient. In addition, a considerable proportion of patients do not respond sufficiently to the treatment. ImmUniverse is a large collaborative consortium of 27 partners funded by the Innovative Medicine Initiative (IMI), which is sponsored by the European Union (Horizon 2020) and in-kind contributions of participating pharmaceutical companies within the European Federation of Pharmaceutical Industries and Associations (EFPIA). ImmUniverse aims to advance our understanding of the molecular mechanisms underlying two immune-mediated diseases, ulcerative colitis (UC) and atopic dermatitis (AD), by pursuing an integrative multi-omics approach. As a consequence of the heterogeneity among IMIDs patients, a comprehensive, evidence-based identification of novel biomarkers is necessary to enable appropriate patient stratification that would account for the inter-individual differences in disease severity, drug efficacy, side effects or prognosis. This would guide clinicians in the management of patients and represent a major step towards personalized medicine. ImmUniverse will combine the existing and novel advanced technologies, including multi-omics, to characterize both the tissue microenvironment and blood. This comprehensive, systems biology-oriented approach will allow for identification and validation of tissue and circulating biomarker signatures as well as mechanistic principles, which will provide information about disease severity and future disease progression. This truly makes the ImmUniverse Consortium an unparalleled approach.

Background: Endoscopic treatment of post-esophagectomy/gastrectomy anastomotic dehiscence includes Self-Expandable Metal Stents (SEMS), which have represented the “gold standard” for many years, and Endoscopic Vacuum Therapy (EVT), which was recently introduced, showing promising results. The aim of the study was to compare outcomes of SEMS and EVT in the treatment of post-esophagectomy/gastrectomy anastomotic leaks, focusing on oncologic surgery. Methods: A systematic search was performed on Pubmed and Embase, identifying studies comparing EVT versus SEMS for the treatment of leaks after upper gastro-intestinal surgery for malignant or benign pathologies. The primary outcome was the rate of successful leak closure. A meta-analysis was conducted, performing an a priori-defined subgroup analysis for the oncologic surgery group. Results: Eight retrospective studies with 357 patients were eligible. Overall, the EVT group showed a higher success rate (odd ratio [OR] 2.58, 95% CI 1.43–4.66), a lower number of devices (pooled mean difference [pmd] 4.90, 95% CI 3.08–6.71), shorter treatment duration (pmd −9.18, 95% CI −17.05–−1.32), lower short-term complication (OR 0.35, 95% CI 0.18–0.71) and mortality rates (OR 0.47, 95% CI 0.24–0.92) compared to stenting. In the oncologic surgery subgroup analysis, no differences in the success rate were found (OR 1.59, 95% CI 0.74–3.40, I2 = 0%). Conclusions: Overall, EVT has been revealed to be more effective and less burdened by complications compared to stenting. In the oncologic surgery subgroup analysis, efficacy rates were similar between the two groups. Further prospective data need to define a unique management algorithm for anastomotic leaks.

Ulcerative colitis (UC) is a chronic relapsing disorder of the colonic tract, characterized by a dysregulated innate and adaptive immune response to gut microbiota that contributes to the perpetuation of intestinal inflammatory processes. The Interleukin (IL) 23/IL17 axis has been reported to play a key role in UC pathogenesis promoting Th17 cells and cytokines-related immune response. Recently, the blockade of IL23/IL17 pathways has been raised enormous interest in the treatment o several chronic inflammatory disorders. In this review, we summarize the emerging results from clinical trials that evoked both promise and discouragement in IL23/IL17 axis in the treatment of UC. Targeting IL23 p40 through Ustekinumab results safe and effective to induce and maintain clinical remission, low inflammatory indexes, mucosal healing, and a better quality of life. Studies targeting IL23 p19 through Mirikizumab, Risankizumab, Brazikumab and Guselkumab are still ongoing. To date, no clinical studies targeting IL17 pathway are ongoing in UC. IL-17 targeting is thought to have a context-dependent biological effect, based on whether cytokine is selectively targeted or if its function is dampened by the upstream block of IL23.

The potential of endoscopic evaluation in the management of inflammatory bowel diseases (IBD) has undoubtedly grown over the last few years. When dealing with IBD patients, histological remission (HR) is now considered a desirable target along with symptomatic and endoscopic remission, due to its association with better long-term outcomes. Consequently, the ability of endoscopic techniques to reflect microscopic findings in vivo without having to collect biopsies has become of upmost importance. In this context, a more accurate evaluation of inflammatory disease activity and the detection of dysplasia represent two mainstay targets for IBD endoscopists. New diagnostic technologies have been developed, such as dye-less chromoendoscopy, endomicroscopy, and molecular imaging, but their real incorporation in daily practice is not yet well defined. Although dye-chromoendoscopy is still recommended as the gold standard approach in dysplasia surveillance, recent research questioned the superiority of this technique over new advanced dye-less modalities [narrow band imaging (NBI), Fuji intelligent color enhancement (FICE), i-scan, blue light imaging (BLI) and linked color imaging (LCI)]. The endoscopic armamentarium might also be enriched by new video capsule endoscopy for monitoring disease activity, and high expectations are placed on the application of artificial intelligence (AI) systems to reduce operator-subjectivity and inter-observer variability. The goal of this review is to provide an updated insight on contemporary knowledge regarding new endoscopic techniques and devices, with special focus on their role in the assessment of disease activity and colorectal cancer surveillance.

Introduction: Patients’ quality of life impairment together with a heavy burden to the NHS and society are caused by chronic inflammatory diseases. Their treatment substantially improved with the advent of biological drugs (such as adalimumab), but these drugs are very expensive. At present, the patent protection of adalimumab (Humira®) has expired, and a biosimilar (Hyrimoz®) has been approved. Since the biosimilar price is expected to be lower as compared with the originator’s, the present Drug Budget Impact analysis tries to evaluate whether and how much profitable the biosimilar availability will be for the Italian NHS, in terms of cost containment (savings). Methods and results : The time horizon in the analysis model is five years. The initial overall number of patients treated with adalimumab is estimated (based on the Italian population, the disease prevalence rates, the proportion of patients under treatment and adalimumab market share) and kept constant in time. However, the model assumes that, year by year, patients in treatment with the originator will partly switch to the biosimilar (based on a prudent estimate of the uptake rate), while (due to a bolder estimate) a larger share of naïve patients will directly start with the biosimilar. Thanks to such assumptions, total number of patients treated with adalimumab (separately with the originator and with the biosimilar) is estimated, with the respective total costs. Conclusions: According to the present analysis, the availability of the biosimilar would generate cumulated savings (in five years) as high as €260 millions for the Italian NHS.

Tofacitinib is an oral small molecule directed against the JAK/STAT pathway, blocking the inflammatory cascade. Oral formulation of tofacitinib has recently been approved for the treatment of patients with moderate–severe ulcerative colitis. Its efficacy and safety have been demonstrated in three phase III clinical trials and confirmed by promising real-life data. The purpose of this review is to summarize the available evidence on the efficacy and safety of tofacitinib and to define its role and position in the treatment algorithms for patients with ulcerative colitis.

Hyaluronan (HA) has proven to be beneficial in the treatment of several diseases. Recently, it has been shown that the local application of HA (IBD98E) improves endoscopic and clinical outcomes in subjects with active distal ulcerative colitis (UC). However, the mechanisms by which this polysaccharide exerts its beneficial effects are unclear. Here, we demonstrated that HA treatment in vitro and in vivo improved mucosal healing by accelerating intestinal epithelial regeneration. Indeed, mice treated with HA showed a faster recovery from colitis and reduced endoscopic signs of mucosal inflammation compared to those receiving saline. Furthermore, histological analysis revealed less ulcerated mucosa in mice treated with HA, characterized by re-epithelialized areas. TSG-6, the secreted product of TNF-stimulated gene-6, is an HA-binding protein shown previously to have tissue-protective properties and promote wound healing. Mucosal levels of TSG-6 increased in UC patients compared to the healthy controls and also after wounding in mice. TSG-6 deletion prevented the beneficial properties of HA in mucosal wound repair, suggesting that the interaction of HA with TSG-6 is crucial for intestinal epithelial regeneration. Overall these results are consistent with HA having a therapeutic effect via the promotion of mucosal healing in patients with ulcerative colitis.

Background: Inflammatory bowel diseases (IBD), ulcerative colitis (UC), and Crohn’s disease (CD), represent systematic chronic conditions with a deficient intestinal absorption. We first attempt to investigate the serum bile acids (sBAs) profile in a large cohort of IBD patients to evaluate changes under anti-TNF alpha treatment. Methods: Forty CD and 40 UC patients were enrolled and BAs were quantified by high-pressure liquid chromatography-electrospray-tandem mass spectrometry (HPLC-ES-MS/MS). Up to 15 different sBAs concentrations and clinical biomarkers where added to a Principal Component Analysis (PCA) to discriminate IBD from healthy conditions and treatment. Results: PCA allowed a separation into two clusters within CD (biologic-free patients and patients treated with anti-TNF alpha drugs and healthy subjects) but not UC. The first included CD. CD patients receiving anti-TNF alpha have an increase in total sBAs (4.11 ± 1.23 μM) compared to patients not exposed. Secondary BAs significantly increase after anti-TNF alpha treatment (1.54 ± 0.83 μM). Furthermore, multivariate analysis based on sBA concentration highlighted a different qualitative sBAs profile for UC and CD patients treated with conventional therapy. Conclusion: According to our results, anti-TNF alpha in CD restores the sBA profile by re-establishing the physiological levels. These findings indicate that, secondary BAs might serve as an indirect biomarker of the healing process.

IBD98-M is a delayed-release formulation of mesalamine (mesalazine) and SH with a potential therapeutic role in ulcerative colitis (UC). A total of 51 patients with a modified Ulcerative Colitis Disease Activity Index (UCDAI) score of ≥4 and ≤10, and a modified UCDAI endoscopy subscore ≥1 were randomized for 6 weeks of double-blind treatment with IBD98 0.8 g/day or IBD 1.2 g/day or placebo. The efficacy and safety of IBD98-M in mild to moderate active UC were primarily evaluated. At week 6, 1 (5.9%), 2 (12.5%), and 2 (11.1%) patients receiving IBD98-M 0.8 g, IBD98-M 1.2 g, and placebo, respectively, (p > 0.999) achieved clinical remission. Higher clinical response was seen in IBD98-M 1.2 g (31.3%) versus placebo (16.7%) and endoscopic improvement in IBD98-M 0.8 g (29.4%) versus placebo (22.2%) was seen. Fecal calprotectin levels were reduced in IBD98-M groups versus placebo (p > 0.05). IBD98-M patients achieved significant improvement in physical health summary score component of the SF-36 (p = 0.01 and p = 0.03 respectively) compared to placebo. IBD98-M did not meet the primary end point but had higher clinical response (1.2 g/day) and endoscopic improvement (0.8 g/day) compared to placebo. The safety result shown that IBD98-M treatment was safe and well tolerated in this patient population. No new safety signals or unexpected safety findings were observed during the study. Further trials with different stratification and longer follow-up may be needed to evaluate the efficacy.

Antiadhesion molecules are effective and safe in patients with ulcerative colitis (UC). Etrolizumab, a monoclonal antibody targeting both α 4 β 7 and α E β 7 , represents a promising therapy for patients with UC, since this novel mechanism of action may be effective in blocking leukocyte recruitment both at the vascular and at the mucosal level. Preliminary studies show that etrolizumab is effective in inducing clinical response and remission, and mucosal healing. Moreover, new predictors of response have recently been identified, opening the way to a tailored therapeutic approach. This review of the literature aims to present and discuss the most recent evidence on etrolizumab in UC, focusing on the clinical implications of the use of etrolizumab in UC.