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Background EUS-guided biliary drainage (EUS-BD) with Lumen Apposing Metal Stent (LAMS) is a mini-invasive approach for jaundice palliation in distal malignant biliary obstruction (D-MBO) not amenable to ERCP, with good efficacy and not exiguous adverse events. Aims and methods From January 2015 to December 2019, we retrospectively enrolled all the EUS-BD with electrocautery-enhanced LAMS for biliary decompression in unresectable D-MBO and failed ERCP. Primary study aims were to evaluate technical/clinical success and AEs rate. In case of maldeployment, we estimated the efficacy of an intra-operative rescue therapy. Secondary aims were to assess the jaundice recurrence and gastric outlet obstruction symptoms. Results Thirty-six EUS-BD were enrolled over a cohort of 738 patients (ERCP cannulation failure rate was 2.6%): 31 choledocho-duodenostomy and 5 cholecystogastrostomy. A pre-loaded guidewire through the LAMS was systematically used in case of common bile duct ≤ 15 mm or scope instability for a safe/preventive biliary entryway in case of intra-procedural complications. Technical success was 80.6% (29/36 patients). Seven cases of LAMS maldeployment during EUS-guided choledocho-duodenostomy were successfully treated with RT by an over-the-wire fully-covered Self-Expandable Metal Stent (FC-SEMS). The FC-SEMS was released through the novel fistula tract in endoscopic fashion in 5/7 cases and transpapillary in percutaneous-transhepatic-endoscopic rendezvous (1/7) and laparoscopic-endoscopic rendezvous (1/7) in the two remaining cases. The total efficacy of rescue therapy was 100%. Same-session duodenal SEMS was placed in 17 patients with optimal gastric outlet obstruction management. Final clinical success was 100% and no other late adverse events or FC-SEMS migration were observed. Conclusion EUS-BD with LAMS is effective for jaundice palliation after ERCP failure but with considerable adverse events. Maldeployment remains a serious complication with fatal evolution if not correctly recognized/managed. Rescue therapy must be promptly applied especially in tertiary-care centers with highly skilled endoscopists, interventional radiologist and dedicated surgeon.

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, naive to ADA and naive to anti-tumor necrosis factors; group B, naive 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

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.

No real-life study on the comparative effectiveness of Vedolizumab (VDZ), Adalimumab (ADA), and Golimumab (GOL) in ulcerative colitis (UC) is currently available.To compare the effectiveness of the three biologics in consecutive patients with UC.A three-arms propensity score-adjusted analysis was performed using the Inverse Probability of Treatment Weighting method.463 treatments (VDZ: n = 187; ADA: n = 168; GOL: n = 108) were included (median follow-up: 47.6 weeks). At 12 weeks (n = 463), a steroid-free remission was reported in 24.1% patients in the VDZ group, in 33.3% patients in the ADA group, and in 30.6% patients in the GOL group (p = n.s. for all comparisons). At 52 weeks (n = 377), a steroid-free remission was reported in 51.5% patients in the VDZ group, in 31.2% patients in the ADA group, and in 29.4% patients in the GOL group (p = 0.002 for VDZ vs. ADA, p = 0.001 for VDZ vs. GOL, p = n.s. for ADA vs. GOL). Cox survival analysis demonstrated that patients treated with VDZ had reduced probability of treatment discontinuation compared to those treated with ADA (HR: 0.42, 95% CI 0.28-0.64, p 0.001) and GOL (HR: 0.30, 95% CI 0.19-0.46, p 0.001), while patients treated with ADA had reduced risk of treatment discontinuation compared to those treated with GOL (HR: 0.71, 95% CI 0.50-1.00, p = 0.048).VDZ was superior to ADA and GOL at 52 weeks and as treatment persistence, while ADA showed a superior treatment persistence compared to GOL.

Purpose: To assess the usefulness of a dedicated questionnaire for patients with inflammatory bowel diseases (IBD) treated with biological drugs for the detection of ocular extraintestinal manifestations (EIMs). IBD can cause extraintestinal symptoms including ocular complaints which are frequently ignored and may be associated with significant morbidity, including blindness. Methods: We developed a questionnaire, named Ocular Manifestations in IBD Screening (OMIS) questionnaire, after agreement between gastroenterologists and ophthalmologists. The questionnaire was administered by a non-ophthalmologist physician to 96 IBD patients treated with biological drugs. Results: 35 patients (36.5%) were selected for the ophthalmologic examination on the basis of a positive screening test. Ocular EIMs were detected in 29 of 35 patients (83%). Conclusion: A specific questionnaire can be useful for non-ophthalmologist physicians in a real world setting in order to select patients to be addressed to an ophthalmological visit, creating an integrated multidisciplinary clinical team, to improve management of IBD in order to prevent disability and guarantee quality of life.

Background Clinical data on the use of Adalimumab (ADA) biosimilar ABP 501 in inflammatory bowel disease (IBD) are lacking. Methods SPOSAB ABP 501 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). All consecutive patients with Crohn’s Disease (CD) or Ulcerative Colitis (UC) treated with ABP 501 from the introduction of the drug in Sicily (February 2019) to February 2020 (12 months) were enrolled. Patients were divided into 3 groups (group A: naive to ADA and naive to anti-TNFs; group B: naive to ADA and previously exposed to anti-TNFs; group C: switch from ADA originator to ABP 501). The primary end-point was the assessment of safety, in terms of rate of serious adverse events (SAEs). Secondary end-point was the evaluation of effectiveness, in terms of clinical response and steroid-free clinical remission at 12 weeks for group A and B, and as treatment persistency for all 3 groups. Results 559 patients (median age 39 years; CD 88.0%, UC 12.0%) were included [group A: 189 (33.8%); group B: 30 (5.4%); group C: 340 (60.8]. Overall, the mean follow-up was 8.7 months (median 10.0 months, interquartile range: 6.0–12.0 months), and the total follow-up time was 403.4 patient-years. 36 SAEs occurred in 36 patients (6.4%), with an incidence rate of 8.9 per 100 person-years (PY), and 22 of them caused the withdrawal of the drug (incidence rate: 5.5 per 100 PY). The incidence rate of SAEs was higher among patients in group A compared with group C (17.4 vs. 4.8 per 100 PY; incidence rate ratio=3.61; p Conclusion This is the first prospective study on the use of ADA biosimilar ABP 501 in IBD. 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.

Background The efficacy of Ustekinumab (UST) on Crohn’s disease (CD) associated spondyloarthropathy (SpA) was evaluated neither in randomized controlled trials nor in real-world studies. Web-based data from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) were extracted to perform a multicentre, real-world assessment of the effectiveness of UST on CD-associated SpA Methods All consecutive CD patients with active SpA at the initiation of the treatment with UST from January 2019 (the date on which the drug became available for clinical practice in Sicily) to August 2019 were extracted from the SN-IBD cohort. The study outcomes were evaluated at 8 and 24 weeks. The primary outcome was the articular response, defined as the disappearance of objective signs of arthritis (swelling and/or articular stiffness) and resolution of pain. As ancillary end-points, the clinical response (reduction of Harvey-Bradshaw Index ≥ 3 compared with baseline with a concomitant reduction of at least ≥ 50% of steroid dosage compared with baseline) and the steroid-free remission (Harvey-Bradshaw Index < 5 without steroids use) were assessed. Results Out of 131 total patients treated with UST, 30 consecutive patients (22.9%) had active SpA at baseline (axial SpA: 3/30; peripheral SpA: 18/30; axial plus peripheral SpA: 9/30). After 8 weeks, 10 patients (33.3%) reported an articular response [0/3 patients with axial SpA, 7/18 patients (38.9%) with peripheral SpA, and 3/9 patients (33.3%) with axial and peripheral SpA]. After 24 weeks, 13 patients (43.3%) had an articular response [0/3 patients with axial SpA, 10/18 patients (55.5%) with peripheral SpA, and 3/9 patients (33.3%) with axial and peripheral SpA]. None of these 13 responders was taking systemic steroids at 24 weeks. The concomitant presence of a clinical response on intestinal symptoms was associated with the articular response at 24 weeks at univariable analysis (OR 5.14, CI 1.09-32.70, p=0.038). Conclusion UST obtained a response on articular symptoms in nearly half of the patients with CD and active SpA at baseline after 24 weeks. The rate of response was higher in case of peripheral arthropathy. The articular response was associated with the clinical response on intestinal symptoms.

Background Cross-sectional studies have assessed the prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with inflammatory bowel disease (IBD). However, longitudinal studies are more suitable to capture dynamic changes. Our aim was to investigate the prevalence and progression of NAFLD in a cohort of IBD patients using validated non-invasive tools. The role of metabolic, disease-related and genetic factors as predictors of NAFLD was also assessed. Methods IBD patients without known chronic liver disease were enrolled between 2019 and 2021. NAFLD was defined as Hepatic Steatosis Index (HSI) ≥ 36 or controlled attenuation parameter (CAP) ≥288 dB/m. Demographic data, traditional risk factors for NAFLD, biochemical tests and disease features were retrospectively collected in a dedicated database at the time of IBD diagnosis (defined as baseline) and at the last follow-up visit. PNPLA3 rs738409 C>G and TM6F2 E167K C>T polymorphisms were also investigated. Univariate and multivariate logistic regression analysis were performed to identify risk factors for NAFLD at baseline and at the end of follow-up. Results 227 consecutive patients (mean age 46.1 ± 13.4 years, 48.7% males, 57% Crohn’s disease, mean disease duration 9.4 ±7.5 years) were enrolled. Laboratory data at the time of diagnosis were available for 64 patients. The mean HSI was 30.9 ± 4.9 and 8/64 eligible patients (12.5%) had NAFLD at baseline. Male sex (odds ratio [OR]: 5.6; 95% confidence interval [CI] 3.1–8.9; P = 0.02) and body mass index (BMI) (OR: 1.4, 95% CI 1.1–2.9; P = 0.0008) were significantly associated with NAFLD at baseline. 11/64 (17.1%) patients developed NAFLD, accounting for an incidence rate of 4.0/100 PY; this was predicted only by changes in BMI over time (OR: 13.6, 95% CI 4.8–19.5; P = 0.001). At the last follow-up visit, NAFLD was diagnosed in 31.2% (71/227) according to HSI and in 21.1% (48/227) according to CAP. Among 8 patients with NAFLD at baseline, HSI worsened in 6 patients (41.0 ± 3.3 vs 44.0 ± 5.2), while two patients had steatosis regression. At the end of follow-up, age (P = 0.01), BMI (P = 0.002) and previous surgery (P = 0.01) were independently associated with NAFLD. Conclusion Our study confirms that NAFLD is common in patients with IBD. Variables related to IBD were not associated with incident NAFLD. Age, BMI and previous surgery were independently associated with NAFLD progression, suggesting a pathogenetic role of gut microbiota and impairment in bile acids metabolism. Our results suggest the need for active surveillance for NAFLD in patients with IBD.

The effectiveness of Ustekinumab (UST) on Crohn's disease (CD)-associated spondyloarthropathy (SpA) is currently unknown.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.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).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.

Background and Aims There are few clinical data on Adalimumab (ADA) biosimilars in inflammatory bowel disease. Methods SPOSAB ABP 501 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease. All consecutive patients treated with ADA biosimilar ABP 501 from the introduction of the drug in Sicily (February 2019) to February 2020 (12 months) were enrolled to assess its safety and effectiveness. Patients were divided into 3 groups: group A, naïve to ADA and naïve to anti-TNFs; group B, naïve to ADA, previously exposed to anti-TNFs; group C: switched from ADA originator to ABP 501. Results 559 patients (median age 39 years; CD 88.0%, UC 12.0%) were included, with a follow-up time of 403.4 patient-years. Thirty-six SAEs occurred in 36 patients [(6.4% - incidence rate (IR): 8.9 per 100 person-years (PY)]. The IR of SAEs was higher among patients in group A compared with group C (17.4 vs. 4.8 per 100 PY; IR ratio=3.61; p 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.

Background Prevalence of NAFLD has recently been reported increased in inflammatory bowel disease (IBD) with conflicting results due to heterogeneity of published studies, especially in the diagnostic definition of NAFLD. The increased risk of NAFLD might be related to traditional risk factors but also to IBD-related factors. The role of genetic markers has been addressed only in one study. The aim of our study has been to assess the prevalence of NAFLD and fibrosis in a homogeneous cohort of patients with IBD, assessing the role of metabolic, disease-related and genetic factors. Methods the diagnosis of NAFLD was based on transient fibroelastometry findings (CAP ≥288 dB/m) and HSI (Hepatic Steatosis Index). Demographic data, traditional risk factors for NAFLD (BMI, lipid profile), comorbities, laboratory tests, disease features (type of IBD, duration, extent, extraintestinal manifestations, relapses/year, disease activity, previous surgery, therapy) were registered in a dedicated database. PNPLA3 rs738409 C>G single nucleotide polymorphism, encoding for I148M protein variant, was investigated by Taqman assay. Results 208 consecutive patients were enrolled: 120 males, 121 Crohn’s disease, 87 ulcerative colitis, mean age 46,4 ± 15,2 years. 26 patients (12,5%) were on steroids, 121 on biologics. The prevalence of NAFLD was 20,7% with mean HSI being 38,3 ± 4,7.On univariate analysis, patients with NAFLD were older (54,6 ± 11,1 years), had higher BMI (28,1 ± 3,9 vs. 24,1 ± 3,8), had more frequently hypertension and high level of LDL and tryglicerides. No significant difference was found as far as concerns gender, number of relapses, extraintestinal manifestations, disease activity and duration and ongoing therapy. Medium stiffness value was higher in patients with NAFLD (6,4 ± 2,4 vs. 4,8 ± 2,2 KPa). CG phenotype of PNAPL3 was more frequent among NAFLD patients, though the result was not significant. On multivariate analysis age, BMI, previous surgery and level of stiffness > 6,9 kPa were independently related to NAFLD. Conclusion This single center cross-sectional study shows that, by using transient elastography, the prevalence of NAFLD in IBD is 20,7% with a significantly increase of liver stiffness and development of fibrosis. NAFLD was related to traditional risk factors (age, BMI, lipid profile) and to previous ileal resection, the last probably due to changes of gut microbiota. Neither intestinal inflammation and drugs nor genetic testing for PNAPL3 seem to be related to the development of NAFLD. Longitudinal studies are warranted to assess the progression of fibrosis and the role of therapeutic interventions.

Background Data on prevalence of extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) range from 6% up to 47%. Recently, several red flags and questionnaires have been proposed for early diagnosis of articular manifestations. Our aim was to analyse the prevalence of EIMs in a single-centre prospective cohort, using a comprehensive questionnaire developed by our group to detect all EIMs (EMAIL questionnaire). Methods Patients with IBD attending our Clinic from November 2017 to January 2019 were interviewed using a two-part questionnaire, the first part for clinical-demographic data and the second part for EIMs. Patients positive to screening were referred for multidisciplinary approach. Results Two hundred and six IBD patients were interviewed, 114 (55.3%) Crohn’s disease (CD) and 92 (44.7%) ulcerative colitis (UC), 52.4% male, mean age 46.7 years (SD ± 15,2). Sixty (53%) CD patients and 48 (52%) UC patients, in total 108, had history of at least one EIM. Articular EIMs were found in 49 patients (24%); peripheral arthritis was found in 14% (29/206), axial arthritis in 9.7% (20 patients): seven patients (3.4%) had ankylosing spondylitis, 13 (6.3%) sacroiliitis. Cutaneous EIMs were detected in 39 patients (19%), erythema nodosum in 15 patients (7.3%), pyoderma gangrenosum in 9 (4.4%), psoriasis in 15 (7.3%) and folliculitis in 7 (3.4%). Ocular EIMs were observed in 35 patients (17%): uveitis in 7 patients (3.4%), conjunctivitis in 8 (3.9%), optic neuritis in 2, glaucoma in 2 patients, cataract in 13 (6,3%), dry eye in 4 (1.9%), central serous chorioretinopathy in 1. Hepatobiliary EIMs were observed in 31 patients (15%): 26 steatosis (12.6%), 5 (2.4%) primary sclerosing cholangitis. Four (2%) patients had DVT. Articular EIMs were more frequent in CD patients (p = 0.001). Skin manifestations were more frequent in female (p = 0.002) in CD (p = 0,032) and related with IBD activity ( Conclusion The questionnaire developed by our group proved to be a sensitive screening tool. Articular and cutaneous EIMs are more frequent in CD, hepatobiliary EIMs are more frequent in UC. A gender difference has been found since cutaneous EIMs are more frequent in females, hepatobiliary more in males. Cutaneous EIMs and DVT are related with IBD activity.

Background No real-life study aiming at comparing at the same time the effectiveness of vedolizumab (VDZ), adalimumab (ADA), and golimumab (GOL) in Ulcerative colitis (UC) is currently available. Methods Data of consecutive patients with UC treated with VDZ, ADA, and GOL from June 2015 to December 2018 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). A three-arms propensity score-adjusted analysis was performed to reduce bias caused by imbalanced covariates at baseline, including the proportion of TNF-α inhibitor naïve and non-naïve patients, using the Inverse Probability of Treatment Weighting (IPTW) method. The effectiveness was evaluated at 8 weeks, 52 weeks, and as treatment persistence at the end of follow-up. The clinical endpoints were steroid-free clinical remission (partial Mayo score Results A total of 463 treatments (VDZ: n = 187; ADA: n = 168; GOL: n = 108) were included, with a median follow-up of 47.6 weeks (IQR 20.0–85.9). At 8 weeks, a clinical benefit was achieved in 70.6% patients treated with VDZ, in 68.5% patients treated with ADA, and in 67.6% patients treated with GOL (p = n.s. for all comparisons). After 52 weeks, VDZ showed better rates of clinical benefit compared with both ADA (71.6% vs. 47.5; OR: 2.79, 95% CI 1.63–4.79, p < 0.001) and GOL (71.6% vs. 40.2%; OR: 3.77, 95% CI 2.08–6.80, p < 0.001), while the difference between ADA and GOL was not significant. Cox survival analysis demonstrated that patients treated with VDZ had a reduced probability of treatment discontinuation compared with those treated with ADA (HR: 0.42, 95% CI 0.28–0.64, p < 0.001) and GOL (HR: 0.30, 95% CI 0.19–0.46, p < 0.001), while patients treated with ADA had a reduced risk of treatment discontinuation compared with those treated with GOL (HR: 0.71, 95% CI 0.50–1.00, p = 0.048). Post-treatment mucosal healing rates showed a numerical but non-significant difference in favour of VDZ (48.1%) compared with ADA and GOL (38.0% and 34.6%, respectively). Conclusion In the first study comparing at the same time the clinical effectiveness of VDZ, ADA, and GOL in UC patients via propensity score-adjusted analysis, VDZ was superior to both subcutaneous agents at 52 weeks and as treatment persistence, while ADA showed a superior treatment persistence compared with GOL.

BACKGROUND We report a prospective, nationwide cohort evaluating the safety and effectiveness of CT-P13. METHODS A structured database was used to record serious adverse events (SAEs), clinical remission/response, inflammatory biomarkers (CRP and calprotectin), and endoscopic findings. RESULTS Eight hundred ten patients with inflammatory bowel disease (IBD) (452 Crohn's disease [CD]) were enrolled. Four hundred fifty-nine patients were naive to anti-TNFα (group A), 196 had a previous exposure (group B), and the remaining 155 were switched to CT-P13 (group C). All patients were included in the safety evaluation with a mean follow-up of 345 ± 215 days and a total number of 6501 infusions. One hundred fifty-four SAEs were reported (19%), leading to cessation of the biosimilar in 103 subjects (12.7%). Infusion reactions were 71, leading to cessation of the biosimilar in 53 subjects (6.5%), being significantly more frequent in patients pre-exposed to anti-TNFα (P = 0.017). The efficacy of therapy was calculated in 754 IBD patients, with a mean follow-up of 329 ± 202 days. Forty-eight patients had a primary failure (6.4%), and 188 (25.6%) lost response during follow-up. Six hundred twenty-eight (364 CD) and 360 IBD patients (222 CD) completed the follow-up at 6 and 12 months, respectively. At 12 months, patients without loss of response were 71%, 64%. and 82% in groups A, B, and C, respectively (log rank P = 0.01). Clinical/endoscopic scores and inflammatory biomarkers dropped significantly in CD and UC patients (P = 0.01 and P < 0.0001) compared with baseline. CONCLUSIONS In this large prospective cohort, no further signals of difference in safety and effectiveness of CT-P13 in IBD has been observed.

Background Anti-tumour necrosis factors (anti-TNFs) have greatly improved therapeutic strategies for the treatment of inflammatory bowel diseases (IBDs). However, a significant number of patients do not respond or lose response over time (LOR). The aim of this retrospective prospective study was to evaluate patients (patients) treated with anti-TNFs as first-line treatment, with subsequent LOR, defined as recurrence of disease activity during maintenance therapy. We determine the prevalence of LOR and its management. Methods Three-hundred forty patients with IBDs were included: 65% had Crohn’s disease and 35% ulcerative colitis. Mean age at diagnosis was 31,5 years and medium time between diagnosis and start of biologic treatment was 72 months. Among 300 patients treated with anti-TNFs, LOR occurred in 33%, 38% was in treatment with Infliximab, 55% with Adalimumab, and 7% with Golimumab and it was statistically related with smoke (p = 0.028), type of drug (p = 0.001) and with the duration of treatment (p = 0.019). Results Among patients with LOR, 88% had a persistent clinical activity, evaluated by clinical scores (HBI and pMayo score) and 56% had a persistent endoscopic activity, evaluated by endoscopic scores (SES-CD and Mayo). After the LOR, 56% of patients optimised treatment for medium time of 7,8 month, 31% switched to another Anti-TNF, 7% swapped to a different class of biologics (Vedolizumab or Ustekinumab) and 4% had surgery as a treatment strategy. During treatment with anti-TNF as second-line treatment, LOR occurred in 17 patients. Anti-TNFs was the third line therapy in 3 patients, while Vedolizumab in 13. Only 2 patients in treatment with Vedolizumab had a second LOR and started Ustekinumab. Conclusion Loss of response occurred frequently in patients treated with biologics. Optimisation of treatment was not efficacious during a long period and the use of another biologic (anti-TNF or another class) is the more suitable strategy in our centre, with success in 35% of patients who lose response.

Background Currently, there are no randomised controlled trials focussing on direct comparisons between biologics in Crohn’s disease (CD), while there is an unmet need to better understand and compare the effectiveness of these drugs. We performed a multicentre, 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 (SN-IBD). A propensity score analysis was performed using the Inverse Probability of Treatment Weighting (IPTW) method. The effectiveness was evaluated at 12 weeks, 52 weeks, and as treatment persistence at the end of follow-up. The clinical endpoints were steroid-free clinical remission (Harvey–Bradshaw Index < 5 without steroid use) and clinical response (reduction of the Harvey–Bradshaw Index ≥ 3 points with a concomitant decrease of steroid dosage compared with baseline). The sum of the two outcomes was defined as a clinical benefit. The achievement of endoscopic response (a reduction of Simple Endoscopic Score for CD ≥ 50% compared with baseline) or mucosal healing (Simple Endoscopic Score for CD ≤ 2) was assessed after at least 6 months of treatment. Results A total of 585 treatments (VDZ: n = 277; ADA: n = 308) were included, with a median follow-up of 56.0 weeks (IQR 24.0–104.0). After 12 weeks, a clinical benefit was achieved in 64.3% patients treated with VDZ and in 83.1% patients treated with ADA (p = 0.11 in propensity score analysis), while at 52 weeks a clinical benefit was observed in 54.0% patients treated with VDZ and in 69.1% patients treated with ADA (p = 0.33 in propensity score analysis). The median treatment persistences for VDZ and ADA were 52 weeks and 64 weeks, respectively. Cox survival analysis weighted for IPTW showed no significant difference in the probability of treatment discontinuation between the two drugs (HR for VDZ=1.20; p = 0.34). Post-treatment endoscopic response and mucosal healing rates were similar between the two drugs (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). Conclusion This is the first real-life study comparing VDZ and ADA in CD patients via propensity score-adjusted analysis. Even if crude rates of all clinical outcomes were higher for ADA compared with VDZ, such differences were not significant when patients’ characteristics at baseline were weighted by propensity score.