Current Knowledge on Breast Implant-Associated Anaplastic Large Cell Lymphoma: Evidence from Italian Ministry of Health Registry Data.

BACKGROUND: Accurate estimation of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) incidence is crucial for assessing breast-implant-associated risk. However, the size of the implanted population worldwide is unknown, making it challenging to appropriately estimate this figure. This study aims to provide a new reliable and reproducible method to estimate the breast-implanted-population (BIP), reporting a reliable annual BIA-ALCL incidence estimate. Moreover, we discuss all activities performed over the past decade in collecting complete histories, managing, and monitoring outcomes of each Italian case. METHODS: Data from the National Breast Implant Registry and from manufacturers have been used to define a new formula to estimate the BIP at risk of developing a breast-implant-related event. From the BIA-ALCL registry, complete information on Italian cases has been collected and analysed. Overall survival is estimated by the Kaplan-Meier curve. RESULTS: From 2010 to June 2024, 111 BIA-ALCL cases were recorded in Italy. The estimated incidence rate showed an upward trend, ranging from 2.68 to 6.35 cases per 100,000 patient-years. Thanks to newly promoted disease awareness, most patients had a complete response to treatment, resulting in a three-year overall survival rate estimate of 98.2%. CONCLUSIONS: The BIP formula showed to be an innovative, effective and reproducible tool to make a reliable estimation of the implanted population, confirming that BIA-ALCL is a rare disease with an incidence rate estimate varying from 2.7 to 6.3 cases/100.000 patient-years in the last five years. Eleven-year experience in this field also confirmed that this disease has a favorable prognosis if properly treated. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Adalimumab Biosimilar in Pediatric Inflammatory Bowel Disease: A Retrospective Study from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD).

BACKGROUND: The utilization of anti-tumor necrosis factor-α (anti-TNF-α) biosimilars in inflammatory bowel disease (IBD) is constantly increasing. However, pediatric data are limited. This study aimed to assess the effectiveness and safety of adalimumab biosimilar (ADL-BioS) in pediatric IBD patients. METHODS: All consecutive pediatric IBD patients from the Sicilian Network for Inflammatory Bowel Disease cohort treated with ADL-BioS from 2019 to 2021 were recruited. Remission at weeks 14 and 52, treatment persistence, and adverse events were the endpoints of this study. Factors associated with clinical remission and treatment persistence were examined. RESULTS: There were 41 patients in total. Nine (22%) patients were switched from the reference product to ADL-BioS. Two patients had multiple switches. Eleven months was the median follow-up period. Clinical remission was attained by 70.7% and 72.0% of patients on weeks 14 and 52, respectively. Four (9.8%) adverse events occurred (10.1/100 person-year). Treatment persistence was 85.4% at 1 and 2 years. Patients with a longer duration of disease had a higher probability of stopping their treatment (p = 0.036). CONCLUSIONS: This is the first real-world study that particularly addresses the use of ADL-BioS in pediatric IBD. With high rates of treatment persistence and a low frequency of non-serious side effects, ADL-BioS seems to be effective.

Ustekinumab is a promising option for the treatment of postoperative recurrence of Crohn's disease.

BACKGROUND AND AIM: Postoperative recurrence (POR) following ileocolonic resection is a major concern in patients with Crohn's disease (CD). The role of ustekinumab (UST) in this setting is poorly known. METHODS: All consecutive CD patients with a baseline colonoscopy at 6-12 months from ileocolonic resection showing POR (Rutgeerts score ≥ i2) who were treated with UST after the baseline colonoscopy and with an available post-treatment endoscopy, were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical success, assessed at the end of follow-up. Reasons for clinical failure included mild clinical relapse (Harvey-Bradshaw index 5-7), clinically relevant relapse (Harvey-Bradshaw index > 7), and need for new resection. RESULTS: Forty-four patients were included (mean follow-up: 17.8 ± 8.4 months). The baseline postoperative colonoscopy showed severe POR (Rutgeerts score i3 or i4) in 75.0% of patients. The post-treatment colonoscopy was performed after a mean of 14.5 ± 5.5 months following initiation of UST. Endoscopic success was reported in 22 out of 44 (50.0%) patients, of whom 12 (27.3%) achieved a Rutgeerts score i0 or i1. Clinical success at the end of follow-up was reported in 32 out of 44 patients (72.7%); none of the 12 patients with clinical failure had achieved endoscopic success at post-treatment colonoscopy. CONCLUSIONS: Ustekinumab could be a promising option for the treatment of POR of CD.

Effectiveness and Safety of Vedolizumab in Inflammatory Bowel Disease: A Comprehensive Meta-analysis of Observational Studies.

BACKGROUND AND AIMS: Many observational studies on the use of vedolizumab [VDZ] in patients with Crohn's disease [CD] and ulcerative colitis [UC] have been published in the past few years. We aimed to comprehensively summarise its effectiveness and safety by pooling data only from observational studies. METHODS: PubMed/Medline and Embase were systematically searched for observational studies on patients with CD and UC treated with VDZ through December 2021. The rates of clinical remission and overall adverse events were the primary outcomes. The rates of steroid-free clinical remission, clinical response, mucosal healing, C-reactive protein normalisation, loss of response, VDZ dose escalation, colectomy, serious adverse events, infections, and malignancies were considered as secondary outcomes. RESULTS: In all, 88 studies comprising 25 678 patients [13 663 with CD and 12 015 with UC] met the inclusion criteria. In patients with CD, the pooled estimate rates of clinical remission were 36% at induction and 39% at maintenance. In patients with UC, the pooled estimate rates of clinical remission were 40% at induction and 45% at maintenance. The pooled estimate of incidence rate of adverse events was 34.6 per 100 person-years. At multivariable meta-regression analysis, studies with increased male proportion were independently associated with higher rates of clinical remission and steroid-free clinical remission at both induction and maintenance, and clinical response at maintenance in patients with CD. Studies with increased disease duration were independently associated with higher mucosal healing rates at maintenance in patients with UC. CONCLUSIONS: Observational studies demonstrated extensively the effectiveness of VDZ, with a reassuring safety profile.

The effectiveness of ustekinumab and vedolizumab as third-line biologic therapy in patients with Crohn's disease.

BACKGROUND: The effectiveness of Ustekinumab (UST) and Vedolizumab (VDZ) in patients with Crohn's disease (CD) as third-line biologic therapies is unclear. AIMS: We performed a multicentre, real-world assessment of the effectiveness of UST and VDZ among highly-refractory patients with CD. METHODS: Data of consecutive patients with CD treated with UST and VDZ as third-line biologic therapy until December 2021 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). RESULTS: 143 patients (UST: n = 113; VDZ: n = 30) were included. At the end of induction, the rates of clinical response (CR) were 61.9% for UST and 60.0% for VDZ (p = 1.00), with steroid-free clinical remission (SFCR) achieved in 38.1% of patients in the UST group and 43.3% of patients in the VDZ group (p = 0.75). After 52 weeks of observation, the rates of CR were 65.9% for UST and 71.4% for VDZ (p = 0.77), while the rates of SFCR were 51.8% for UST and 57.1% for VDZ (p = 0.78). At multiple Cox proportional hazard regression model, age (HR 0.98; p = 0.04) and need for systemic steroids at baseline (HR 3.29; p = 0.003) were found to be independent predictors of treatment discontinuation. CONCLUSIONS: Both VDZ and UST showed high effectiveness as third-line biologic therapy in CD, without significant differences between them.

Real-life experience of infliximab biosimilar in pediatric-onset inflammatory bowel disease: data from the Sicilian Network for Inflammatory Bowel Disease.

OBJECTIVE: To provide data on the use of infliximab biosimilars (IFX-BioS) in children with inflammatory bowel disease (IBD). METHODS: A multicenter, observational, retrospective study was performed among the cohort of the Sicilian Network for IBD. All consecutive IBD children who had at least completed the induction with IFX-BioS from its introduction in Sicily to January 2021 were enrolled. Clinical remission at weeks 14 and 52, treatment persistence, and adverse events were the study outcomes. RESULTS: Eighty-seven patients [Crohn's disease (CD): 57.5% and ulcerative colitis (UC): 42.5%] were included: 75 (86.2%) were antitumor necrosis factor-α (anti-TNF-α) agent naïve, while three (3.45%) were switched from the originator to IFX-BioS. Twenty (23%) patients were multiply switched from the biosimilar CT-P13 to SB2 or GP1111 or vice versa. The median follow-up time was 15 months. Clinical remission was achieved by 55.2 and 65.5% of patients at weeks 14 and 52, respectively, with no differences between CD and UC. Dose escalation was needed in 8.0 and 35.7% of patients during induction and maintenance, respectively. Nine adverse events occurred (incidence rate: 6.13/100 person-year). Treatment persistence was 90.8% at 1 year and 75.7% at 2 years (patients on IFX-BioS at 2 years, n = 28). The risk of treatment discontinuation was higher in patients with extraintestinal manifestations ( P = 0.018) and in those who were nonnaïve to anti-TNF-α ( P = 0.027). CONCLUSION: This is the largest cohort of pediatric IBD patients treated with IFX-BioS. Real-life data show that IFX-BioS is efficacious in IBD children, with high percentages of treatment persistence and a low incidence of nonserious adverse events.

Managing Pediatric Foreign Body Ingestions: A 10-Year Experience.

BACKGROUND: Foreign body (FB) ingestion is a common global issue in pediatrics. Most of the ingested FBs pass through the gastrointestinal tract, but up to 20% of cases require endoscopic removal. In this study, we retrospectively reviewed all pediatric cases of FB ingestion requiring endoscopic removal over a 10-year period in a tertiary hospital to compare the symptoms at presentation and outcomes with those reported in previous studies and to assess the association of the outcomes with patient and FB characteristics. METHODS: A retrospective chart review of children 16 years or younger who underwent upper endoscopy for FB ingestion from 2008 to 2018 in a tertiary hospital was included. Data on demographics, clinical presentation, characteristics of FBs, endoscopic findings, and outcomes were reviewed. The clinical data were further evaluated to determine the circumstances surrounding FB ingestion, FB management, and patient outcomes. Descriptive analysis of the data was performed using medians, frequencies, and percentage; χ2 or Fisher exact test was used to assess the dependence between categorical variables. RESULTS: Eighty-six patients (median age, 5.1 years; 67% males) underwent endoscopy for suspected FB ingestion, with a confirmation rate of 91%. Coins were the most commonly ingested FBs (n = 49, 57%). Most patients were symptomatic (84%); 97% of patients in whom the FB had an esophageal location and all patients in whom the FB was not detected by endoscopy were symptomatic (P = 0.007). The most frequent symptoms were drooling (70%) and unexplained crying (48%). Unexplained crying was more common in younger than in older patients (P < 0.001). The FB was more likely to be located in the esophagus in patients with drooling (P < 0.001) and dysphagia (P < 0.001). The distribution of FB location differed according to the FB type, with coins most frequently located in the esophagus and sharp and other FBs in the stomach (P = 0.023). Only 7 patients (8%) developed mild FB-related mucosal injury. No complications occurred during FB removal. All patients had an uneventful outcome. CONCLUSIONS: Foreign body ingestion is common among younger children, and the clinical presentation can be variable. The presence or absence of symptoms, as well as the type of symptom, could aid clinicians in implementing diagnosis and proper management approaches in patients who ingest FBs requiring endoscopy.

SPOSAB ABP 501: A Sicilian Prospective Observational Study of Patients with Inflammatory Bowel Disease Treated with Adalimumab Biosimilar ABP 501.

BACKGROUND AND AIM: There are few clinical data on Adalimumab (ADA) biosimilars in inflammatory bowel disease. We aimed to perform a multicenter, observational, prospective study on safety and effectiveness of ADA biosimilar ABP 501 in patients with inflammatory bowel disease. METHODS: All consecutive patients from the cohort of the Sicilian Network for Inflammatory Bowel Disease treated with ADA biosimilar ABP 501 from February 2019 to February 2020 were enrolled. Patients were divided into three groups: group A, naïve to ADA and naïve to anti-tumor necrosis factors; group B, naïve to ADA and previously exposed to anti-tumor necrosis factors; and group C: switched from ADA originator to ABP 501. RESULTS: A total of 559 patients (median age 39 years; Crohn's disease 88.0%, ulcerative colitis 12.0%) were included, with a follow-up time of 403.4 patient-years. Thirty-six serious adverse events occurred in 36 patients (6.4%; incidence rate [IR]: 8.9 per 100 person-years [PY]). The IR of serious adverse events was higher among patients in group A compared with group C (17.4 vs 4.8 per 100 PY; IR ratio = 3.61; P < 0.001) and among patients in group B compared with group C (16.4 vs 4.8 per 100 PY; IR ratio = 3.42; P = 0.041). Among ADA-naïve patients (group A + B), 188 (85.8%) had a clinical response after 12 weeks, including 165 (75.3%) who achieved steroid-free remission. Higher treatment persistence estimates were reported for patients in group C compared with groups A and B (log-rank P < 0.001). CONCLUSIONS: Safety and effectiveness of ABP 501 seem to be overall similar to those reported for ADA originator. Switching from originator to ABP 501 was safe and effective.

Chest wall infiltration is a critical prognostic factor in breast implant-associated anaplastic large-cell lymphoma affected patients.

BACKGROUND: Breast implant-associated anaplastic large-cell lymphoma is a rare disease with a favourable prognosis if adequately treated. Same staged patients have usually a similar prognosis and outcomes, but in our experience, IIA-staged patients have a wider prognosis with outcomes that vary from complete disease response to death. This study aimed to understand and identify all the factors that could influence the prognosis of this group of patients and verify if their prognosis matches the stage they belong to. MATERIAL AND METHODS: Patients in stage IIA have been divided into two subgroups: IIAb with lymphoma extension towards the glandular tissue and IIAcw with tumour extension towards the chest-wall. The overall survival (OS) and event-free survival (EFS) of 64 BIA-ALCL cases were evaluated for each staged group. RESULTS: Significant differences of OS and EFS between IIAb and IIAcw patients (log-rank p = 0.046 and log-rank p = 0.018, respectively) were observed and poor prognosis joined IIAcw- and IV-staged patients. CONCLUSION: Chest-wall infiltration is a critical prognostic factor in BIA-ALCL patients as it influences the possibility of performing a surgical radical tumour extirpation. Our results could represent valid assistance for the physicians in choosing the most appropriate BIA-ALCL prognostic category and treatment and could promote further wider studies to provide stronger evidence on a possible revision of the MDA TNM classification.

The management of colonic polyps in children: a 13-year retrospective study.

The aim of this study was to describe the frequency, major symptoms, and characteristics of colonic polyps in a cohort of children. A retrospective chart review of patients aged ≤ 18 years who were diagnosed with colonic polyp(s) from 2006 to 2019 in a tertiary hospital was included. Data collected included demographics, clinical presentation, interval of time between the onset of symptoms and the endoscopic diagnosis of colonic polyps, family history, characteristics of the polyp, and associated lesions. Over the study period, 35 Caucasian children were diagnosed with juvenile colonic polyps. Twenty-three patients (65.7%) were males. Lower gastrointestinal bleeding of a mean duration of 5.3 ± 4.9 months was the presenting symptom in nearly all cases (n = 34, 97%), and it was isolated in 17 patients. Clinical presentation did not significantly vary according to the age or the location or size of the polyp (p = 0.262, p = 1.000, and p = 0.149, respectively). The polyps were mainly located in the left colon (n = 29, 83%). Right colonic polyps were significantly larger than left colonic polyps (p = 0.037).Conclusion: Lower gastrointestinal bleeding represents the most common presentation of colonic polyps in children. Right-sided colonic polyps occur and may be even larger than left-sided ones. A total colonoscopy is therefore mandatory for all cases of suspected colonic polyps. This study represents a real-life contribution, and it can help improve the management strategies of this condition in childhood. What is Known: • Colonic polyps are quite common in children. • The majority of pediatric colonic polyps are solitary, benign, and located in the left colon. What is New: • Right-sided colonic polyps occur and may be even larger than left-sided ones. • A total colonoscopy is mandatory for all cases of suspected colonic polyps.

The SPOSIB SB2 Sicilian Cohort: Safety and Effectiveness of Infliximab Biosimilar SB2 in Inflammatory Bowel Diseases, Including Multiple Switches.

BACKGROUND: No data on the recently introduced infliximab (IFX) biosimilar SB2 in inflammatory bowel disease (IBD) are available. METHODS: The Sicilian Prospective Observational Study of Patients With IBD Treated With Infliximab Biosimilar SB2 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease. All consecutive IBD patients starting the IFX biosimilar SB2 from its introduction in Sicily (March 2018) to September 2019 (18 months) were enrolled. RESULTS: Two hundred seventy-six patients (Crohn disease: 49.3%, ulcerative colitis: 50.7%) were included: 127 (46.0%) were naïve to IFX and naïve to anti-tumor necrosis factor medications (anti-TNFs), 65 (23.5%) were naïve to IFX and previously exposed to anti-TNFs, 17 (6.2%) were switched from an IFX originator to SB2, 43 (15.6%) were switched from the biosimilar CT-P13 to SB2, and 24 (8.7%) were multiply switched (from IFX originator to CT-P13 to SB2). The cumulative number of infusions of SB2 was 1798, and the total follow-up time was 182.7 patient-years. Sixty-seven serious adverse events occurred in 57 patients (20.7%; incidence rate: 36.7 per 100 patient-year), and 31 of these events caused the withdrawal of the drug. The effectiveness after 8 weeks of treatment was evaluated in patients naïve to IFX (n = 192): 110 patients (57.3%) had steroid-free remission, while 56 patients had no response (29.2%). At the end of follow-up, 72 patients (26.1%) interrupted the treatment, without significant differences in treatment persistency estimations between the five groups (log-rank P = 0.15). CONCLUSIONS: The safety and effectiveness of SB2 seem to be overall similar to those reported for the IFX originator and CT-P13.

A propensity score weighted comparison of vedolizumab and adalimumab in Crohn's disease.

BACKGROUND AND AIM: There are no head-to-head randomized controlled trials between biologics in Crohn's disease (CD). We aimed to perform a multicenter, real-life comparison of the effectiveness of vedolizumab (VDZ) and adalimumab (ADA) in CD. METHODS: Data of consecutive patients with CD treated with VDZ and ADA from January 2016 to April 2019 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. The effectiveness was evaluated at 12, 52 weeks, and as failure-free survival at the end of follow up. Propensity score analysis was performed using the inverse probability of treatment weighting method. RESULTS: Five hundred eighty-five treatments (VDZ: n = 277; ADA: n = 308) were included (median follow-up: 56.0 weeks). After 12 weeks, a clinical response was achieved in 64.3% patients treated with VDZ and in 83.1% patients treated with ADA (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.38-1.10, P = 0.107), while at 52 weeks, a clinical response was observed in 54.0% patients treated with VDZ and in 69.1% patients treated with ADA (OR 0.77, 95% CI 0.45-1.31, P = 0.336). Cox survival analysis weighted for propensity score showed no significant difference in the probability of failure-free survival between the two drugs (hazard ratio = 1.20, 95% CI 0.83-1.74, P = 0.340). Post-treatment endoscopic response and mucosal healing rates were similar between the two groups (endoscopic response: 35.3% for VDZ and 25.5% for ADA, P = 0.15; mucosal healing: 31.8% for VDZ and 33.8% for ADA, P = 0.85). CONCLUSIONS: In the first study comparing VDZ and ADA in CD via propensity score analysis, the drugs showed comparable effectiveness and a similar safety profile.

Effectiveness of Ustekinumab on Crohn's Disease Associated Spondyloarthropathy: Real-World Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD).

BACKGROUND: The effectiveness of Ustekinumab (UST) on Crohn's disease (CD)-associated spondyloarthropathy (SpA) is currently unknown. RESEARCH DESIGN AND METHODS: All consecutive CD patients with active SpA at the initiation of the treatment with UST were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was the articular response at 8 and 24 weeks, defined as the disappearance of objective signs of arthritis (swelling and/or articular stiffness) and resolution of pain. RESULTS: Thirty CD patients with active SpA at the initiation of the treatment with UST were assessed. At 24 weeks, 13 patients (43.3%) had an articular response, including 10/18 patients (55.5%) with peripheral SpA and 3/9 patients (33.3%) with axial and peripheral SpA. No patient with axial SpA experienced an articular response. The drop of mean as Harvey-Bradshaw Index values from baseline to week 24 was higher in patients with articular response compared with non-responders (3.8 ± 2.4 vs. 1.3 ± 2.8, p = 0.02). CONCLUSIONS: Our real-world, multicentre experience showed that UST was able to obtain a response on articular symptoms in nearly half of the patients with CD and active SpA after 24 weeks of treatment.

Effectiveness and safety of vedolizumab in biologically naïve patients: A real-world multi-centre study.

BACKGROUND: Biologically naïve patients with inflammatory bowel disease treated with vedolizumab (VDZ) are largely underrepresented in real-world cohorts. A multi-centre, observational cohort study was performed on the effectiveness and safety of VDZ in biologically naïve subjects with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Data of consecutive biologically naïve patients with CD and UC treated with VDZ from July 2016 to December 2019 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. RESULTS: A total of 172 consecutive patients (CD: N = 88; UC: N = 84; median age 66.0 years) were included, with a median follow-up of 58.8 weeks. After 14 weeks, a clinical response was reported in 68.2% of patients with CD and 67.9% of patients with UC treated with VDZ, including 45.5% patients in the CD group and 46.4% patients in the UC group who achieved steroid-free remission. After 52 weeks, a clinical response was reported in 77.4% of CD and in 73.8% of UC patients treated with VDZ, including 59.7% patients in the CD group and 60.7% patients in the UC group who achieved steroid-free remission. CONCLUSIONS: This study demonstrates the effectiveness and safety of VDZ as a first-line biological, particularly among elderly patients.

Biosimilars: The viewpoint of Italian patients with inflammatory bowel disease.

BACKGROUND: The viewpoint on biosimilars among patients with inflammatory bowel diseases (IBD) is largely unknown. AIMS: We aimed at exploring the confidence and opinion on biosimilars among Italian patients with IBD. METHODS: An anonymous, 20-item, questionnaire was sent via e-mail to all members of the Italian IBD patients' association (AMICI Onlus). Three sets of questions were formulated: 1: Characteristics of respondents; 2: The use of biologics and biosimilars in clinical practice; 3: General opinions on biologics and biosimilars. RESULTS: Of the 4,302 total surveys sent, there were 1,749 respondents (response rate: 40.6%). There was an equal distribution between males and females (48.3% and 51.7%, respectively), and between patients with Crohn's disease and ulcerative colitis (46.9% and 51.3%, respectively), while most of the patients were aged between 19 and 45 years and between 46 and 65 years (45.5% and 42.0%, respectively). Approximately 45% of the respondents declared to have never been informed about the existence of biosimilars. The great majority of patients (73.9%) did not know if originators and biosimilars could be considered equivalent, or if efficacy or safety of biosimilars could be lower than those of originators. Approximately half of the respondents (53.5%) had no idea that the use of low-cost biosimilars could be useful to increase the overall economic resources for the treatment of IBD. CONCLUSIONS: An extensive lack of knowledge and confidence in biosimilars exists among Italian patients with IBD. Efforts carried out by scientific societies and IBD patients' associations are required to overcome this issue.

Effectiveness of very low-volume preparation for colonoscopy: A prospective, multicenter observational study.

BACKGROUND: The effectiveness of colonoscopy strictly depends on adequate bowel cleansing. Recently, a 1 L polyethylene glycol plus ascorbate (PEG-ASC) solution (Plenvu; Norgine, Harefield, United Kingdom) has been introduced on the evidence of three phase-3 randomized controlled trials, but it had never been tested in the real-life. AIM: To assess the effectiveness and tolerability of the 1 L preparation compared to 4 L and 2 L- PEG solutions in a real-life setting. METHODS: All patients undergoing a screening or diagnostic colonoscopy after a 4, 2 or 1 L PEG preparation, were consecutively enrolled in 5 Italian centers from September 2018 to February 2019. The primary endpoints of the study were the assessment of bowel cleansing success and high-quality cleansing of the right colon. The secondary endpoints were the evaluation of tolerability, adherence and safety of the different bowel preparations. Bowel cleansing was assessed through the Boston Bowel Preparation Scale. Adherence was defined as consumption of at least 75% of each dose, while tolerability was evaluated through a semi-quantitative scale. Safety was systematically monitored through adverse events reporting. RESULTS: Overall, 1289 met the inclusion criteria and were enrolled in the study. Of these, 490 patients performed a 4 L-PEG preparation (Selgesse®), 566 a 2 L-PEG cleansing (Moviprep® or Clensia®) and 233 a 1 L-PEG preparation (Plenvu®). Bowel cleansing by Boston Bowel Preparation Scale was 6.5 ± 1.5 overall and 6.3 ± 1.5, 6.2 ± 1.5, 7.3 ± 1.5 (P < 0.001) in the subgroups of 4 L, 2 L and 1 L-PEG preparation, respectively. Cleansing success was achieved in 72.4%, 74.1% and 90.1% (P < 0.001), while a high-quality cleansing of the right colon in 15.9%, 12.0% and 41.4% (P < 0.001) for 4 L, 2 L and 1 L-PEG preparation groups, respectively. The 1 L preparation was the most tolerated compared to the 2 and 4 L-PEG solutions in the absence of serious adverse events within any of the three groups. Multiple regression models confirmed 1 L PEG-ASC preparation as an independent predictor of overall cleansing success, high-quality cleansing of the right colon and of tolerability. CONCLUSION: This study supports the effectiveness and tolerability of 1 L PEG-ASC, also showing it is an independent predictor of overall cleansing success, high-quality cleansing of the right colon and of tolerability.

Persistence on Anti-Tumour Necrosis Factor Therapy in Older Patients with Inflammatory Bowel Disease Compared with Younger Patients: Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD).

BACKGROUND AND OBJECTIVE: Older people with inflammatory bowel disease (IBD) appear to have a lower response to anti-tumour necrosis factor (TNF) therapy, with more frequent complications than younger patients. The objective of this study was to assess persistence on therapy and the safety of anti-TNF therapy in older patients (aged ≥ 60 years). METHODS: We retrospectively reviewed the database of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD), extracting data regarding IBD patients aged ≥ 60 years and controls < 60 years of age at their first course of anti-TNF treatment. Data concerning persistence on therapy over the first year of treatment (primary objective) together with data on reasons for treatment withdrawal, concomitant diseases and treatments were collected. RESULTS: We identified 114 anti-TNF-naϊve patients aged ≥ 60 years (median age 64 years, range 60-80 years; 47 males) compared with 330 younger controls aged < 60 years (median age 39 years, range 18-59 years; 57 males). Older patients with Crohn's disease (n = 73) showed a significantly lower persistence with every kind of anti-TNF therapy (whether analysed together [p < 0.001] or separately for intravenous and subcutaneous [SC] therapy) than younger controls, whereas older patients with ulcerative colitis (n = 41) showed a lower persistence when combining all kinds of anti-TNF treatment (p = 0.004) and for SC therapy. Secondary failures, infections, and neoplasias, but not primary failure, occurred more frequently in older IBD patients than in younger controls. CONCLUSION: Despite a comparable number of primary failures, older IBD patients treated for the first time with anti-TNF agents showed lower treatment persistence due to higher rates of secondary failure, adverse events, infections, and tumours than younger patients in the first year of follow-up. The reasons for this difference still remain unclear.

Effectiveness and safety of biologics in pediatric inflammatory boweldisease: Real-life data from the Sicilian Network.

BACKGROUND: Biological therapies have modified the disease course of pediatric inflammatory bowel disease (IBD) and are routinely used in clinical practice. Our observational study aims to evaluate effectiveness and safety of biologics in IBD. METHOD: Clinical benefit and safety data of 93 children with IBD, receiving biologics (Infliximab - IFX, Adalimumab - ADA, Golimumab - GOL) from January 2013 to December 2017, were extracted from the cohort of the Sicilian Network of IBD. RESULTS: Among 87 children aged 7-17 years (63 Crohn's disease [CD], 24 Ulcerative colitis [UC]), 101 out of 108 biologic treatments were considered. Evaluation of 74 biologic treatments in CD patients at 26, 52, 104 weeks showed clinical benefit rates of 84.2%, 93.3%, 66.7% with IFX (n= 38) and 88.9%, 84.4%, 65.2% with ADA (n= 36). Biologic treatments (n=27) evaluated in the UC group at 26, 52, 104 weeks, led to clinical benefit rates of 85.7%, 83.3%, 50% in IFX subgroup (n=21) and 40%, 50%, 33% in the ADA subgroup (n=5), respectively. One patient treated with GOL showed 100% clinical benefit at 26 and 52 weeks. Overall adverse events (AEs) rate was 9.25%. Six younger children, <6 years, receiving 8 treatments (4 ADA, 4 IFX) presented a clinical remission rate of 75% at 12 weeks and 25% at 52 weeks. AEs rate was 25% in this group. CONCLUSION: Our data show that biologic therapy in children, even at a younger age, is effective in allowing long-term remission with a good safety profile.

Effectiveness and safety of Ustekinumab for the treatment of Crohn's disease in real-life experiences: a meta-analysis of observational studies.

Background: The aim of this meta-analysis was to estimate the effectiveness and safety of Ustekinumab in Crohn's disease (CD) reported by observational studies.Research design and methods: PubMed/Medline and Embase were systematically searched through September 2019. Only real-life observational studies were included.Results: Thirteen studies comprising 1450 patients met the inclusion criteria. Ustekinumab was administered subcutaneously at induction among 7 studies, while in 6 studies the intravenous formulation was used. At induction (8-16 weeks), the pooled estimate rates of clinical response and remission were 56% (95% CI: 43-68%; range: 16-94%; I2 = 94%) and 34% (95% CI: 25-45%; range: 15-58%; I2 = 90%), respectively. The rate of clinical response was higher among studies which employed the subcutaneous compared with the intravenous induction (68% vs. 38%, p = 0.01). At maintenance, the pooled estimate rates of clinical response, clinical remission, endoscopic response, and endoscopic remission were 62% (95% CI: 50-73%; range: 42-89%; I2 = 89%), 40% (95% CI: 28-54%; range: 26-73%; I2 = 90%), 56% (95% CI: 37-73%; range: 20-77%; I2 = 87%), and 19% (95% CI: 11-30%; range: 7-31%; I2 = 67%), respectively.Conclusions: Ustekinumab is an effective treatment in patients with CD with a reassuring safety profile. The subcutaneous induction seems to be superior to the intravenous one.

Lupus-like reactions in patients with inflammatory bowel disease treated with anti-TNFs are insidious adverse events: data from a large single-center cohort.

Objectives: Very few data on the incidence, predictors, and clinical outcomes of lupus-like reactions (LLRs) in patients with inflammatory bowel disease (IBD) treated with anti-TNFs have been reported. Materials and methods: All records of consecutive IBD patients who started a treatment with an anti-TNF from January 2006 to June 2018 were retrospectively reviewed. Patients were defined as having LLR by the presence of immunologic abnormalities (positivity for ANA and/or anti-ds-DNA), along with clinical features that included at least two of the following: arthralgia, fatigue, fever, cutaneous manifestations, or serositis, which had a clear temporal association with exposure to the anti-TNFs, and resolved without recurrence once the drug was discontinued. Results: 760 patients (1059 total treatments with anti-TNFs) were included. Participants contributed a total of 2863.5 person-years of follow-up, during which 16 cases of LLRs (2.1% of patients) were reported, accounting for an incidence rate of 5.6 per 1000 person-years. Female gender and being former smokers were more prevalent in the LLR group (75.0% versus 44.1%, p = .02; and 18.8% versus 5.4%, p = .037, respectively), with a hazard ratio of 4.40 (95% CI: 1.40-13.81; p = .011) and 4.87 (95% CI: 1.37-17.38; p = .015), respectively, at Cox regression analysis. All LLRs resolved following discontinuation of the drug after a mean of 8.1 ± 4.2 weeks. Ten patients required corticosteroids to control severe symptoms. Conclusions: In this large cohort of patients treated with anti-TNFs with long follow-up, LLRs were rare adverse events, more common in women and former smokers, occurring with nonspecific and insidious clinical features.