Factors correlated with transmural healing in patients with Crohn's disease in long-term clinical remission on anti-TNF medication.

BACKGROUND & AIMS: Transmural healing is a long-term target for patients with Crohn's disease. Factors contributing to its promotion are poorly understood. This study assessed factors correlating with transmural healing based on intestinal ultrasound, in patients in long-term clinical remission on anti-TNF. METHODS: 68 consecutive Crohn's patients on adalimumab (50) or infliximab (18) therapy with clinical remission ≥1 year were recruited and assessed for clinical features, trough serum levels of anti-TNF and intestinal ultrasound findings. Univariate analysis and multivariate binary logistic regression analysis identified variables independently associated with bowel wall thickening behavior. RESULTS: Sixty eight patients were in remission for a mean of 4.1 years. Thirty-six patients (52.9 %) showed anti-TNF trough levels below the normal threshold. Twenty-two patients (38.4 %) showed transmural healing, 32 (47.1 %) transmural response, and 26 (38.2 %) no treatment response. Transmural healing correlated with higher BMI and lower baseline bowel wall thickening; transmural response correlated with short Crohn's disease duration, high drug levels, and with non-stricturing phenotype. Treatment non-response correlated with lower BMI, lower drug levels, higher baseline bowel wall thickening, and stricturing phenotype. CONCLUSIONS: Lack of transmural healing in stable remission Crohn's patients on anti-TNF therapy is multifactorial, mainly due to low anti-TNFs trough levels, development of strictures, and higher baseline bowel wall thickening at treatment initiation.

Management of Post-Operative Crohn's Disease: Knowns and Unknowns.

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by relapsing-remission phases. CD often requires surgical intervention during its course, mainly ileo-cecal/ileo-colonic resection. However, surgery in CD is not curative and post-operative recurrence (POR) can happen. The management of CD after surgery presents challenges. Ensuring timely, effective, and safe therapy to prevent POR is essential but difficult, considering that approximately 20-30% of subjects may not experience endoscopic POR and that 40-50% will only exhibit intermediate lesions, which carry a low risk of mid- and long-term clinical and surgical POR. Currently, there are two accepted intervention strategies: early post-operative prophylactic therapy (systematically or based on the patient's risk of recurrence) or starting therapy after confirming endoscopic POR 6-12 months after surgery (endoscopy-driven prophylactic therapy). The risk of overtreatment lies in exposing patients to undesired adverse events, along with the costs associated with medications. Conversely, undertreatment may lead to missed opportunities to prevent bowel damage and the necessity for additional surgery. This article aims to perform a comprehensive review regarding the optimal strategy to reduce the risk of POR in CD patients and the current therapeutic options.

Rates of Adverse Events in Patients With Ulcerative Colitis Undergoing Colectomy During Treatment With Tofacitinib vs Biologics: A Multicenter Observational Study.

INTRODUCTION: Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics. METHODS: A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints. RESULTS: Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents ( P = 0.047) and of late VTE with vedolizumab ( P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00). DISCUSSION: Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy.

Ophthalmological Manifestations in Inflammatory Bowel Diseases: Keep an Eye on It.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. However, a broad spectrum of extraintestinal manifestations (EIMs) is associated with IBD, affecting several organs and systems, such as the skin, musculoskeletal and hepatobiliary systems, and, not least, the eye. Approximately 10% of IBD patients can develop ocular EIMs (O-EIMs) with a higher prevalence in Crohn's disease (CD). Eye-redness, photophobia, pain, and blurred vision are the common symptoms, with a wide rate of severity and clinical impact on the quality of life. This narrative review aims to summarize the prevalence, pathogenesis, and current evidence-based management of O-EIMs, underlying the importance of a holistic approach and specialties collaboration for a prompt diagnosis and treatment. METHODS: PubMed was searched up to December 2023 to identify relevant studies investigating the pathogenesis, epidemiology, and treatment of O-EIMs in IBD patients. RESULTS: The mechanisms underlying O-EIMs are partially unknown, encompassing immune dysregulation, shared antigens between the eye and the gut, genetic predisposition, and systemic inflammation driven by high levels of interleukins and cytokines in IBD patients. The complexity of O-EIMs' pathogenesis reflects in the management of these conditions, varying from topical and systemic steroids to immunomodulatory molecules and biologic therapy, such as anti-tumor necrosis factor (TNF)-alpha. A multidisciplinary approach is the backbone of the management of O-EIMs.

Exploring the link: Porto-sinusoidal vascular disorder and inflammatory bowel disease - A comprehensive narrative review.

Porto-sinusoidal vascular disorder (PSVD) encompasses a group of vascular disorders characterized by lesions involving the portal venules and sinusoids, independent of the presence of portal hypertension (PH), and for which liver biopsy is essential for diagnosis. PSVD has been shown to be common in patients with immune-mediated diseases, including inflammatory bowel disease (IBD). The association between PSVD and the use of thiopurines and thioguanine in patients with IBD has been well established. In addition, research suggests an association between PSVD and IBD, even in cases where patients haven't been exposed to specific medications, probably related to changes in intestinal permeability. The identification and management of patients with known IBD and PSVD is a challenge for gastroenterologists. This narrative review aims to summarize the currently available data on the association between IBD and PSVD and provide practical suggestions for the management of this group of patients.

Lung Involvement in Inflammatory Bowel Diseases: Shared Pathways and Unwanted Connections.

Inflammatory bowel diseases (IBDs) are chronic, relapsing inflammatory disorders of the gastrointestinal tract, frequently associated with extraintestinal manifestations (EIMs) that can severely affect IBD patients' quality of life, sometimes even becoming life-threatening. Respiratory diseases have always been considered a rare and subsequently neglected extraintestinal manifestations of IBD. However, increasing evidence has demonstrated that respiratory involvement is frequent in IBD patients, even in the absence of respiratory symptoms. Airway inflammation is the most common milieu of IBD-related involvement, with bronchiectasis being the most common manifestation. Furthermore, significant differences in prevalence and types of involvement are present between Crohn's disease and ulcerative colitis. The same embryological origin of respiratory and gastrointestinal tissue, in addition to exposure to common antigens and cytokine networks, may all play a potential role in the respiratory involvement. Furthermore, other causes such as drug-related toxicity and infections must always be considered. This article aims at reviewing the current evidence on the association between IBD and respiratory diseases. The purpose is to raise awareness of respiratory manifestation among IBD specialists and emphasize the need for identifying respiratory diseases in early stages to promptly treat these conditions, avoid worsening morbidity, and prevent lung damage.

Extraintestinal Cancers in Inflammatory Bowel Disease: A Literature Review.

BACKGROUND: Inflammatory bowel disease (IBD) is a group of chronic multifactorial inflammatory disorders including two major entities: Crohn's disease (CD) and ulcerative colitis (UC). Preliminary evidence suggests that patients with IBD may be at increased risk of developing intestinal and extraintestinal cancers (EICs). Actually, little is known about the association between IBD and EICs, and there is ever-growing concern regarding the safety of immunomodulators and biological therapy, which may represent a risk factor for carcinogenesis. AIMS: The aim of this review is to summarize the evidence regarding the association between IBD and EICs, the safety of immunomodulators and biological therapy and the management of immunomodulators and biologic agents in IBD patients with prior or current EICs. RESULTS: IBD patients have a higher risk of developing different forms of extraintestinal solid organ tumors and hematological malignancies. Immunomodulators and biological therapy may increase the risk of developing some types of EICs and may be consciously used in patients with IBD and current or prior history of malignancy. CONCLUSIONS: Decisions regarding the use of immunomodulators or biological therapies should be made on an individual basis, considering a multidisciplinary approach involving oncologists.

Autoimmune Pancreatitis in Patients with Inflammatory Bowel Disease: A Real-World Multicentre Collaborative ECCO CONFER Study.

BACKGROUND: Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and predictors of complicated AIP course have rarely been reported. METHODS: An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD. RESULTS: We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35 ±â€…16 years]. The majority of Crohn's disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR] = 1.05, p = 0.008), whereas family history of IBD [OR = 0.1, p = 0.03], and CD diagnosis [OR = 0.2, p = 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred. CONCLUSIONS: In this large international cohort of patients with concomitant AIP-IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP course.

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.

Comparison of two strategies for the management of postoperative recurrence in Crohn's disease patients with one clinical risk factor: A multicentre IG-IBD study.

BACKGROUND: The management of postoperative recurrence (POR) in Crohn's disease (CD) after ileo-colonic resection is a highly debated topic. Prophylactic immunosuppression after surgery is currently recommended in the presence of at least one clinical risk factor. OBJECTIVE: Our aim was to determine whether early immunosuppression can be avoided and guided by endoscopy in CD patients with only one risk factor. METHODS: CD patients with only one risk factor for POR, including previous intestinal resection, extensive small intestine resection (>50 cm), fistulising phenotype, history of perianal disease, and active smoking, were retrospectively included. Two groups were formed based on whether immunosuppression was started immediately after surgery ("prophylaxis group") or guided by endoscopy ("endoscopy-driven group"). Primary endpoints were rates of any endoscopic recurrence (Rutgeerts ≥ i2a) and severe endoscopic recurrence (i4) within 12 months after surgery. Secondary outcomes were clinical recurrence rates at 6, 12 and 24 months after surgery. RESULTS: A total of 195 patients were enroled, of whom 61 (31.3%) received immunoprophylaxis. No differences between immunoprophylaxis and the endoscopy-driven approach were found regarding any endoscopic recurrence (36.1% vs. 45.5%, respectively, p = 0.10) and severe endoscopic recurrence (9.8% vs. 15.7%, respectively, p = 0.15) at the first endoscopic evaluation. Clinical recurrence rates were also not statistically different (p = 0.43, p = 0.09, and p = 0.63 at 6, 12, and 24 months, respectively). CONCLUSIONS: In operated CD patients with only one risk factor for POR, immediate immunoprophylaxis does not decrease the rate of early clinical and endoscopic recurrence. Prospective studies are needed to confirm our results.

Noninvasive Assessment of Postoperative Disease Recurrence in Crohn's Disease: A Multicenter, Prospective Cohort Study on Behalf of the Italian Group for Inflammatory Bowel Disease.

BACKGROUND & AIMS: Colonoscopy (CS) is the gold standard to assess postoperative recurrence (POR) in Crohn's disease (CD). However, CS is invasive and may be poorly tolerated by patients. The aim of this study was to prospectively assess the diagnostic accuracy of a noninvasive approach in detecting POR, using the endoscopic Rutgeerts' score (RS) as the reference standard. METHODS: Consecutive patients with CD who underwent ileo-cecal resection were prospectively enrolled in 3 referral Italian centers. Patients underwent CS and bowel ultrasound within 1 year of surgery. Uni- and multivariable analyses were used to assess the correlation between noninvasive parameters and endoscopic recurrence, defined by a RS ≥2. RESULTS: Ninety-one patients were enrolled. Sixty patients (66%) experienced endoscopic POR. The multivariable analysis identified bowel wall thickness (BWT) per 1-mm increase (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.21-4.89; P = .012), the presence of mesenteric lymph nodes (OR, 15.63; 95% CI, 1.48-164.54; P = .022), and fecal calprotectin (FC) values ≥50 mcg/g (OR, 8.58; 95% CI, 2.45-29.99; P < .001) as independent predictors for endoscopic recurrence. The presence of lymph nodes or the combination of BWT ≥3 mm and FC values ≥50 mcg/g correctly classified 56% and 75% of patients, with less than 5% of patients falsely classified as having endoscopic recurrence. Conversely, the combination of BWT <3 mm and FC <50 mcg/g correctly classified 74% of patients with only 4.5% of patients falsely classified as not having endoscopic recurrence. CONCLUSIONS: A noninvasive approach combining bowel ultrasound and FC can be used with confidence for detecting POR in patients with CD without the requirement for CS.

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.

Endoscopic Postoperative Recurrence in Crohn's Disease After Curative Ileocecal Resection with Early Prophylaxis by Anti-TNF, Vedolizumab or Ustekinumab: A Real-World Multicentre European Study.

BACKGROUND: Endoscopic-post-operative-recurrence [ePOR] in Crohn's disease [CD] after ileocecal resection [ICR] is a major concern. We aimed to evaluate the effectiveness of early prophylaxis with biologics and to compare anti-tumour necrosis factor [anti-TNF] therapy to vedolizumab [VDZ] and ustekinumab [UST] in a real-world setting. METHODS: A retrospective multicentre study of CD-adults after curative ICR on early prophylaxis was undertaken. ePOR was defined as a Rutgeerts score [RS] ≥ i2 or colonic-segmental-SES-CD ≥ 6. Multivariable logistic regression was used to evaluate risk factors, and inverse probability treatment weighting [IPTW] was applied to compare the effectiveness between agents. RESULTS: The study included 297 patients (53.9% males, age at diagnosis 24 years [19-32], age at ICR 34 years [26-43], 18.5% smokers, 27.6% biologic-naïve, 65.7% anti-TNF experienced, 28.6% two or more biologics and 17.2% previous surgery). Overall, 224, 39 and 34 patients received anti-TNF, VDZ or UST, respectively. Patients treated with VDZ and UST were more biologic experienced with higher rates of previous surgery. ePOR rates within 1 year were 41.8%. ePOR rates by treatment groups were: anti-TNF 40.2%, VDZ 33% and UST 61.8%. Risk factors for ePOR at 1 year were: past-infliximab (adjusted odds ratio [adj.OR] = 1.73 [95% confidence interval, CI: 1.01-2.97]), past-adalimumab [adj.OR = 2.32 [95% CI: 1.35-4.01] and surgical aspects. After IPTW, the risk of ePOR within 1 year of VDZ vs anti-TNF or UST vs anti-TNF was comparable (OR = 0.55 [95% CI: 0.25-1.19], OR = 1.86 [95% CI: 0.79-4.38]), respectively. CONCLUSION: Prevention of ePOR within 1 year after surgery was successful in ~60% of patients. Patients treated with VDZ or UST consisted of a more refractory group. After controlling for confounders, no differences in ePOR risk were seen between anti-TNF prophylaxis and other groups.

An Objective Comparison of Vedolizumab and Ustekinumab Effectiveness in Crohn's Disease Patients' Failure to TNF-Alpha Inhibitors.

INTRODUCTION: The use of ustekinumab and vedolizumab as second-line therapies in patients with Crohn's disease (CD) in which tumour necrosis factor alpha inhibitors (TNFi) failed is still debated. The aim of this study was to compare, in a large multicenter observational retrospective cohort, the effectiveness of ustekinumab and vedolizumab as second-line therapies, as assessed by clinical and objective outcomes including endoscopy and gastrointestinal imaging. METHODS: Clinical response, remission, and steroid-free remission at weeks 26 and 52 were evaluated in a retrospective propensity score-weighted and propensity score-matched cohort of patients in which TNFi failed. Objective response and remission were evaluated by 1 or more techniques among endoscopy, magnetic resonance/computed tomography enteroclysis, and small bowel ultrasound. RESULTS: A total of 470 patients with CD (239 treated with ustekinumab and 231 treated with vedolizumab) were included in the study. At week 26, clinical outcomes were similar between the 2 groups. At week 52, clinical remission (ustekinumab 42.5% vs vedolizumab 55.5%, P = 0.01) and steroid-free remission (ustekinumab 40.6% vs vedolizumab 51.1%, P = 0.038) rates were significantly higher in vedolizumab-treated patients. Three hundred two patients (hundred thirty-five treated with ustekinumab and hundred sixty-seven treated with vedolizumab) had an objective evaluation of disease activity at baseline and week 52. At week 52, objective response and remission rates were similar between the 2 groups. Clinical response at week 26 predicted steroid-free remission at week 52 in both ustekinumab-treated and vedolizumab-treated patients. Safety profiles were similar between the 2 groups. DISCUSSION: In patients with CD in which TNFi failed, both ustekinumab and vedolizumab showed similar clinical effectiveness after 26 weeks of treatment. At 1 year, vedolizumab was associated with a higher rate of clinical remission when compared with ustekinumab. However, no difference was observed between the 2 groups when objective outcomes were investigated at this time point.

Effectiveness of ustekinumab in patients with refractory Crohn's disease: a multicentre real-life study in Italy.

BACKGROUND: The effectiveness of ustekinumab in patients with refractory Crohn's disease (CD) has been investigated in several real-world studies. However, very few data concerning the real-life experience in Italy have been reported. Therefore, this study assessed the effectiveness of ustekinumab in a large cohort of Italian patients with refractory CD. METHODS: All patients who had started on ustekinumab after failure of or intolerance to antitumour necrosis factor-α (TNF-α) treatment at five tertiary centres between November 2018 and February 2020 were retrospectively enrolled. The coprimary outcome was corticosteroid-free clinical remission, defined as a Harvey-Bradshaw Index (HBI) score of ⩽4, at weeks 26 and 52. The secondary outcomes were changes in the HBI and C-reactive protein (CRP) values at weeks 8, 26, and 52 from baseline and the normalization of CRP in patients with initially abnormal values. RESULTS: Totally, 140 patients who had previously received at least one anti-TNF-α agent were enrolled; 40.0% received two anti-TNF-α agents and 20.0% received vedolizumab. At baseline, 108 patients (77.1%) had HBI scores of >4; of these, 56.5% and 58.3% achieved corticosteroid-free clinical remission at weeks 26 and 52, respectively. Significant decreases in HBI and CRP values were observed at weeks 8, 26, and 52 in the entire study cohort (all p < 0.0001). The CRP values were normalized in 34.9%, 37.8%, and 49.3% of the patients by weeks 8, 26, and 52, respectively. The baseline HBI score of ⩾8 was a negative predictor of corticosteroid-free clinical remission at week 52 (odds ratio: 0.21, 95% confidence interval: 0.08-0.56, p = 0.002). The probability of remaining on ustekinumab after 52 weeks was 92.1%. Eleven (7.9%) patients discontinued ustekinumab (three for adverse events). CONCLUSION: Our study findings confirm the effectiveness and safety of ustekinumab in patients with CD after failure of or intolerance to anti-TNF-α therapy.

Ultrasonography Tight Control and Monitoring in Crohn's Disease During Different Biological Therapies: A Multicenter Study.

BACKGROUND & AIMS: Bowel ultrasonography (BUS) is a noninvasive tool for evaluating bowel activity in Crohn's disease (CD) patients. Aim of our multicenter study was to assess whether BUS helps to monitor intestinal activity improvement/resolution following different biological therapies. METHODS: Adult CD patients were prospectively enrolled at 16 sites in Italy. Changes in BUS parameters [i.e. bowel wall thickening (BWT), lesion length, echo pattern, blood flow changes and transmural healing (TH: normalization of all BUS parameters)] were analyzed at baseline and after 3, 6 and 12 months of different biological therapies. RESULTS: One hundred eighty-eight out of 201 CD patients were enrolled and analyzed (116 males [62%]; median age 36 years). Fifty-five percent of patients were treated with adalimumab, 16% with infliximab, 13% with vedolizumab and 16% with ustekinumab. TH rates at 12 months were 27.5% with an NNT of 3.6. TH at 12 months after adalimumab was 26.8%, 37% after infliximab, 27.2% after vedolizumab and 20% after ustekinumab. Mean BWT improvement from baseline was statistically significant at 3 and 12 months (P < .0001). Median Harvey-Bradshaw index, C-reactive protein and fecal calprotectin decreased after 12 months from baseline (P < .0001). Logistic regression analysis showed colonic lesion was associated with a higher risk of TH at 3 months and a greater BWT at baseline was associated with a lower risk of TH at 3 months [P = .03 (OR 0.70, 95% CI 0.50-0.97)] and 12 months [P = .01 (OR 0.58, 95% CI 0.38-0.89)]. At 3 months therapy optimization during the study was the only independent factor associated with a higher risk of no ultrasonographic response [P = .02 (OR 3.34, 95% CI 1.18-9.47)] and at 12 months disease duration [P = .02 (OR 3.03, 95% CI 1.15-7.94)]. CONCLUSIONS: Data indicate that BUS is useful to monitor biologics-induced bowel activity improvement/resolution in CD.

Effectiveness of adalimumab for ulcerative colitis: A multicentre, retrospective study of clinical practice in Italy.

BACKGROUND: Adalimumab is used to treat ulcerative colitis, but additional effectiveness and safety data are needed. PATIENTS AND METHODS: This retrospective study considered adults with ulcerative colitis treated with adalimumab at 19 hospitals. Clinical data were collected from the start of treatment, after 2, 6 and 12 months, and at the last visit. Outcome measures of effectiveness were treatment duration, reasons for discontinuation and colectomy. RESULTS: We studied 381 patients treated with adalimumab for a median of 12.1 months. Disease activity at the start of treatment was moderate to severe in 262 cases (68.8%) and endoscopic activity was moderate to severe in 339 cases (89.0%). At week 8, clinical responses were observed in 177 cases (46.5%) and clinical remission in 136 cases (35.7%). At 12 months, remission was observed in 128 cases (33.6%). Overall, 44 patients required colectomy, and 170 patients (44.6%) were still taking adalimumab when data were collected. Variables associated with adalimumab discontinuation were concomitant steroid treatment, severe clinical-endoscopic activity at baseline, need for adalimumab intensification and drug-related adverse events. Variables associated with colectomy were concomitant steroid treatment and high baseline C-reactive protein. CONCLUSION: Adalimumab is safe and effective for the treatment of ulcerative colitis.

Does ProCore Fine-Needle Biopsy Really Improve the Clinical Outcome of Endoscopic Ultrasound-Guided Sampling of Pancreatic Masses?

INTRODUCTION: Fine-needle biopsy (FNB) has been suggested to provide better histological samples as compared to endoscopic ultrasound fine-needle aspiration (EUS-FNA). However, studies comparing EUS-FNA and EUS-FNB for pancreatic lesions reported contrasting results. The aim of this study was to compare the clinical performance of EUS-FNA versus EUS-FNB with the ProCore needle for the investigation of pancreatic lesions. METHODS: We reviewed all patients undergoing EUS for the investigation of pancreatic lesions from August 2012 to September 2018. From August 2012 to January 2015, all procedures were performed with standard needles, whereas from February 2015 to September 2018, the use of ProCore needles had been introduced. Data on diagnostic accuracy, number of needle passes, and/or adverse events were collected. RESULTS: Three hundred twenty-four patients were retrospectively evaluated: 190 (58.6%) underwent EUS-FNA and 134 (41.4%) EUS-FNB. Both EUS-FNA and EUS-FNB showed high diagnostic accuracy for malignancy (94% [95% CI: 89-97%] vs. 94% [95% CI: 89-98%]). Notably, there were no differences between EUS-FNA and EUS-FNB in terms of sensitivity, specificity, positive and negative likelihood ratio, histological core tissue retrieval, adverse events, or number of needle passes. However, subgroup analysis noted a higher diagnostic accuracy for 25G EUS-FNB as compared to 25G EUS-FNA (85.7 vs. 55.5%; *p = 0.023). CONCLUSION: EUS-FNB with the ProCore needle is safe and feasible in pancreatic lesions. The ProCore needle did not provide any advantage in terms of diagnostic accuracy, sensitivity, specificity, positive and/or negative likelihood ratio, or acquisition of the core specimen; therefore, its routine application is not supported.

Therapies for inflammatory bowel disease do not pose additional risks for adverse outcomes of SARS-CoV-2 infection: an IG-IBD study.

BACKGROUND: Older age and comorbidities are the main risk factors for adverse COVID-19 outcomes in patients with inflammatory bowel disease (IBD). The impact of IBD medications is still under investigation. AIMS: To assess risk factors for adverse outcomes of COVID-19 in IBD patients and use the identified risk factors to build risk indices. METHODS: Observational cohort study. Univariable and multivariable logistic regression was used to identify risk factors associated with pneumonia, hospitalisation, need for ventilatory support, and death. RESULTS: Of the 937 patients (446 with ulcerative colitis [UC]) evaluated, 128 (13.7%) had asymptomatic SARS-CoV-2 infection, 664 (70.8%) had a favourable course, and 135 (15.5%) had moderate or severe COVID-19. In UC patients, obesity, active disease and comorbidities were significantly associated with adverse outcomes. In patients with Crohn's disease (CD), age, obesity, comorbidities and an additional immune-mediated inflammatory disease were identified as risk factors. These risk factors were incorporated into two indices to identify patients with UC or CD with a higher risk of adverse COVID-19 outcomes. In multivariable analyses, no single IBD medication was associated with poor COVID-19 outcomes, but anti-TNF agents were associated with a lower risk of pneumonia in UC, and lower risks of hospitalisation and severe COVID-19 in CD. CONCLUSION: The course of COVID-19 in patients with IBD is similar to that in the general population. IBD patients with active disease and comorbidities are at greater risk of adverse COVID-19 outcomes. IBD medications do not pose additional risks. The risk indices may help to identify patients who should be prioritised for COVID-19 re-vaccination or for therapies for SARS-CoV-2 infection.

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.