BACKGROUND:Few data exist regarding the effectiveness of ustekinumab in inflammatory bowel disease (IBD) patients treated for concomitant psoriasis or psoriatic arthritis. AIMS:to describe the outcomes of IBD patients who received subcutaneous ustekinumab through a dermatological or rheumatological prescription. METHODS:This multicenter, retrospective study included all IBD patients who were started on ustekinumab for concomitant active psoriasis/ psoriatic arthritis, irrespective of IBD activity. The primary endpoint was overall ustekinumab persistence, defined as the maintenance of therapy because of sustained clinical benefit for IBD. RESULTS:Seventy patients (64 Crohn's disease / 6 ulcerative colitis) were enrolled. The median follow-up on ustekinumab therapy was 10.7 months (range, 1.4-67.3). Twelve patients (17.1%) withdrew the treatment after a median of 7.4 months (range, 0.9-23.8). The cumulative probability of maintaining ustekinumab treatment was 97.1% at 6 months and 77.1% at 12 months. Among the 56 patients with baseline active IBD, 34 (60.7%) were in clinical remission at the last follow-up visit. Their cumulative probability of achieving clinical remission was 84.7% and 63.9% at 6 and 12 months, respectively. Two patients stopped ustekinumab for an adverse event. CONCLUSIONS:Subcutaneous ustekinumab had a good effectiveness profile for IBD patients treated for concomitant dermatological or rheumatological conditions.

Inflammatory bowel diseases (IBD) are expected to have an adverse impact on sexual health. Depression and anxiety, common disorders in IBD, are known to be a risk factor for sexual dysfunction. Few data are available on the impact of IBD on relationships, body image and sexual function (SF). The aim of this study was to evaluate how ulcerative colitis (UC) may affected SF. We enrolled 51 consecutive UC patients and 32 controls in current partnership referred to our centre. They were asked to fill in 6 validated questionnaires on quality of life (IBDQ), SF (FSFI or IIEF, ISS), psychological well-being (PGWBI), anxiety/depression (HADS) and couple functioning (DAS). Disease activity was assessed using Partial Mayo Score (PMS) and faecal calprotectin levels. Statistical analysis was performed by Pearson test, Shapiro test, Bartlett test, the Paired Sample T-Test. Partial Component Analysis and the analysis of variance (ANOVA)were evaluated to compare behaviours of patients and controls groups. Many SF indexes were significantly higher for controls than for patients (ISS p = 0.018, for women FSFI p = 0.049, for men IIEF-C p = 0.0007, IIEF-D p = 0.001, IIEF-E p = 0.05; Figure 1). Among patients, no significant correlation was found between disease severity and relationship quality (DAS). For those treated with topical therapy, an inverse correlation was found between sexual discomfort and relationship quality (ISS-DAS, r = −0.68,p = 0.000006); for patients treated with oral/parenteral therapy, the main factor influencing the relationship quality was depression (ISS-HADS Depression, r = −0.5, p = 0.026). In women, SF (FSFI) did not correlate with any of the analysed variables. Our results confirm that UC patients have lower levels of sex life than controls. Well-being and couple cohesion was unaffected by the disease, even in case of topical therapy. Conversely, depression resulted to adversely impact the relationship quality In women, SF appears to be less affected by IBD-related factors

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening event affecting up to 25% of patients during disease course. Intensive intravenous glucocorticoid treatment (IIVT) and early colectomy have reduced mortality to less than 2% in the last four decades. Rescue therapies -Infliximab (IFX) or Cyclosporin (CyA)- may reduce early colectomy in IIVT refractory patients but their impact in the long-term is unclear. Aim of the present study was to evaluate the long-term colectomy rate in patients escaping early colectomy after a severe attack From 2005 to 2016 all patients with ASUC meeting Truelove and Witts criteria modified by Chapman et al. referring to 14 Italian IBD referral centres were retrospectively reviewed. All patients received IIVT. IFX or CyA were used as rescue therapies. Primary outcome was long-term colectomy rate in patients escaping early colectomy (within 3 months). Secondary outcomes were overall need of escalation therapy (defined as need of anti-TNF agents or immunomodulators or steroids) or hospitalisation. Kaplan–Meier survival method was used to estimate the cumulative probability of a colectomy-free course and log-rank test to compare colectomy-free survival distributions in different subgroups. A stepwise regression model was used to look for predictive factors of long-term colectomy In total, 361 patients were enrolled. Of them, 15 (4.2%) underwent early colectomy and 346 avoided colectomy: due to of IIVT response (n = 223,64.5%) or rescue therapy response with IFX (n = 103, 29.7%) or CyA (n = 20, 5.8%). Clinical characteristics of patients. During a median follow-up of 43 months (range 1–156),67 patients (19.4%) required colectomy. The cumulative probability of a colectomy-free course was 92.7, 87, 81.9 and 79.7% after 12, 24, 36 and 60 months, respectively. Colectomy risk was similar in IIVT responders and in rescue therapy responders. During follow-up, 135 (39%) and 109 (31.5%) patients required at least one escalation of therapy and hospitalisation, respectively. At multi-variate analysis none of the covariates considered (age, gender, first or recurrent attack, disease extension, C-Reactive Protein levels, endoscopic severity, steroid/rescue therapy responsiveness, maintenance treatment) was associated to long-term colectomy risk The long-term colectomy risk after an acute severe attack is still relevant and do not seem to be influenced by the severity of the attack, resulting similar both in IIVT responders and in IIVT refractory patients responding to rescue therapies.

In the last few years, adalimumab (ADA) and golimumab (GOL) have been developed as a therapeutic option for ulcerative colitis (UC). Infliximab (IFX) remains the gold standard therapy for severe UC. Mucosal healing (MH) is emerging as primary goal of anti-TNF therapy in UC. Limited data are known about potential early predictors of MH, especially regarding ADA and GOL. A prospective observational study was carried out among the patients with moderate–severe UC who started treatment with IFX, ADA and GOL in monotherapy between January and September 2016 at our centre. The basal therapy with mesalamine was maintained stable during the follow-up period (1 year). Primary non-responder was excluded. Partial Mayo score (PMS), C-reactive protein (CRP) and faecal calprotectin (FC) were assessed before treatment and every 8 weeks during the follow-up. All the patients underwent colonoscopy at baseline and at the end of follow-up or in case of discontinuation of therapy due to loss of response (LOR) or side effects (SE). MH was defined as a Mayo Endoscopic Score ≤ 1. All the colonoscopies were performed by a single-blinded operator. Clinical remission (PMS <2), a normal CRP value (<0.5 mg/dl), and a value of FC <150 mg/kg (chosen on the basis of previous studies1,2) were evaluated as potential predictors of MH. Statistical analysis was carried out using Fisher's test for categorical variables. Forty-seven patients were enrolled, 21 treated with IFX, 12 with ADA, and 14 with GOL. LOR was observed in 18 patients (38%), 3 patients (6%) experienced SE. Twenty-six (55%) patients maintained the therapy until the end of follow-up, 16 of them (62%) showed MH. Overall, 18 of 47 (38%) patients showed MH. A significant correlation between MH and FC <150 mg/kg at Week 8 (p < 0.001) was observed in patients treated with IFX, ADA or GOL evaluated globally, while no correlation was observed between MH and PMS or CRP at the same time point. Correlation between FC and MH in the totality of patients. Correlation between FC and MH in the totality of patients. Same results are achieved considering only the subcutaneous drugs (ADA and GOL) or IFX singularly. Moreover, MH was correlated with FC levels at Week 16 and at Week 24, while PMS and CRP showed a significant correlation with MH only at Week 24. Our results showed that an early drop of FC levels is a good predictor of MH at 1 year in UC patients treated with IFX, ADA or GOL. Therefore, FC could be used as a reliable tool for an early optimisation of anti-TNF treatment in UC patients in order to reach the correct therapeutic target. 1. Costa F et al. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn's disease. Gut, 2005. 2. Guardiola J et al. Faecal level of calprotectin identifies histologic inflammation in patients with ulcerative colitis in clinical and endoscopic remission. Clin Gastroenterol Hepatol, 2014.

Background: Approximately 40% of patients affected by Crohn's Disease (CD) require surgical treatment in their lifetime. An adequate pre-operative management including improvement of nutritional status may decrease the complication rate. An enteral polymeric diet (EPD) enriched with transforming growth factor-beta2 has been shown to be useful in patients with CD, and able to induce remission in pediatric patients. No data is still available about patients with CD scheduled for surgery. The aim of the study was to assess the efficacy of EPD as nutritional support to standard of care diet (SCD) in CD patients undergoing surgery. Methods: We evaluated patients with ileal CD referred to our center and treated with laparoscopic ileo-cecal resection throughout 12 months; we excluded patients with colonic resection in order to have a more homogeneous sample. Medical treatment, Body Mass Index (BMI), serum albumin and hemoglobin were assessed in all patients the day before the surgical procedure. We evaluated the operative and postoperative course (conversion to laparotomy, need for surgical re-treatment in the following three months, days of stay in hospital). We considered as a worse outcome the conversion, the surgical re-treatment, and a stay in hospital exceeding 7 days after surgery. According to nutritional therapy, patients were divided into 2 groups: EPD (SCD with 50g EPD in 210ml of water four times a day) and SCD (without any supplementation). Statistical analysis was performed by Student-t-test for continuous and Fisher exact test for categorical variables. Results: Fifty-eight CD patients underwent surgery in the study period; we recruited 35 CD patients (16 M), treated with ileo-cecal resection. Mean age was 43.8±14.7 years, mean stay in hospital 7.28±3.34 days. Four patients needed a conversion to laparotomy (2 for a massive abscess, 2 for mesentery retraction); 4 patients needed surgical re-treatment (1 the day after surgery, 1 two weeks later, 1 two months later, 1 three months later); eleven patients had a post-surgical stay in hospital of 8 or more days. Ten patients were treated with EPD and 25 with SCD. No difference was observed in medical treatment, hemoglobin, serum albumin or BMI values between the two groups before surgery. Patients treated with EPD showed a better outcome in comparison with SCD (p<0.05). Table 1 Conclusions: Our results showed that EPD, when administered before surgical ileo-cecal resection in CD patients, seems to prevent complications, improving the outcome during the postoperative course and considerably reducing costs.

Background: Therapeutic response to Infliximab (IFX) and Adalimumab (ADA) in patients affected by Crohn's Disease (CD) has been assessed for many years by clinical indices of disease activity; however, recently it has been shown that a combination of both clinical and endoscopic remission leads to a better outcome. As CD involves the whole wall thickness, a transmural healing could be an even more important long-term target in order to reduce the risk of clinical relapse. A gold standard to assess transmural healing is still lacking. The primary aim of our study was to analyze if fecal calprotectin (FC) values correlates with mucosal and parietal healing evaluated by Ultrasound Imaging (US) or Magnetic Resonance Imaging (MRI). The secondary aim was to evaluate mucosal and parietal healing in CD patients treated with anti-TNF with clinical response. Methods: We enrolled 21 consecutive ileal CD patients who reached clinical remission at W6 with IFX or ADA. All patients performed colonoscopy, US and MRI at 1 year. Fecal calprotectin (FC) was evaluated at 6 months and at 1 year. Absence of ulcers was considered as endoscopic healing. A bowel wall thickness (≤3 mm) was considered as transmural healing in MRI and in US. The value of 150mg/Kg of FC was considered the best cut off to identify patients at high risk of clinical relapse. Statistical analysis was performed by Fisher Exact Test. Results: We recruited 21 CD patients (8M), 10 (48%) treated with IFX, 11 (52%) with ADA. After one year of treatment, 9 (42%) patients showed mucosal healing, 7 (33%) patients showed transmural healing with US and 5 (23%) patients showed transmural healing with MRI. Five (23%) patients had FC values ≤150 mg/Kg at 6 months, 10 (48%) patients at one year. We found a correlation between FC values at 6 months and mucosal and parietal healing both with MRI and US. Table 1. Correlation between calprotectin 6 months and MRI 12 months Table 2. Correlation between calprotectin 6 months and endoscopy 12 months On the other hand, FC values at one year correlated with mucosal healing and with parietal healing with US, but not with parietal healing with MRI. Conclusions: Our results showed that, even adopting restrictive criteria, a good response to anti-TNF therapy was observed both for mucosal and transmural healing. Above all, we found a correlation between FC values at 6 months and mucosal and transmural healing, suggesting that FC could be a prognostic marker of therapeutic response and a possible future target of therapy.

Background:The long-term outcome of Crohn's disease (CD) is still suboptimal, as stricturing and perforating disease are frequent and many patients require multiple courses of corticosteroids or surgery.Improving the long-term outcome has been suggested as a novel treatment goal in CD, but evidence-based recommendations on how to accomplish this goal are limited.We assessed the effect of early exposure to immunomodulators (IMM) on the long-term outcome in a large population-based cohort.Methods: All 1162 CD patients from the Inflammatory Bowel Disease South Limburg (IBDSL) registry, diagnosed between 1991 and 2011, followed until 2014, were eligible for this study.Early IMM exposure was defined as having a first thiopurine prescription within 6 months after diagnosis with a treatment duration of at least 3 months.The long-term outcome was studied in terms of CD-related hospitalisation, corticosteroid use, surgery, and the development of strictures or fistulas.To avoid immune-time bias, the first year after diagnosis, including possible events, was censored in all patients.Kaplan-Meier survival analyses were used to determine the unadjusted cumulative probability of an event, and Cox regression modelling was applied to study the association between early IMM use and outcomes, adjusting for confounding by indication of early IMM use by propensity score adjustment.Data were presented as adjusted hazard ratios (aHR) with 95% confidence intervals (95%CI).Results: In total, 1 104 CD patients were followed for more than 12 months.Of these, 223 (20.2%) had early IMM exposure, with an average treatment duration of 4.2 years (SD 3.2).In the group without early IMM exposure (n = 881, 79.7%), 51.0% commenced IMM therapy later in disease course, at an average of 3.4 years (SD 3.7) after diagnosis.The mean follow-up was 6.7 years (SD 3.9) and 9.8 years (SD 5.8) for the early IMM and no early IMM group, respectively.During follow-up, no significant differences were observed in the 10-year hospitalisation risk (28.6% vs 35.5%, aHR 0.78; 95% CI 0.55-1.10), the 10-year surgery risk (15.2% vs 17.4%, aHR 0.65; 95%CI 0.40-1.06),or the 10-year phenotype progression risk (24.1% vs 25.9%, aHR 0.87; 95% CI 0.55-1.38).In contrast, a reduction in the 10-year corticosteroid exposure risk (39.1% vs 45.0%, aHR 0.73; 95% CI 0.54-0.99)was found.Conclusions: In this population-based study, early immunomodulator exposure was associated with a decreased need for corticosteroids, whereas no benefit was observed on the risks of hospitalisation, surgery, or phenotype progression.These findings underline the complexity of changing the natural history of CD and warrants further research to identify the optimal treatment strategy.

Background:The long-term outcome of Crohn's disease (CD) is still suboptimal, as stricturing and perforating disease are frequent and many patients require multiple courses of corticosteroids or surgery.Improving the long-term outcome has been suggested as a novel treatment goal in CD, but evidence-based recommendations on how to accomplish this goal are limited.We assessed the effect of early exposure to immunomodulators (IMM) on the long-term outcome in a large population-based cohort.Methods: All 1162 CD patients from the Inflammatory Bowel Disease South Limburg (IBDSL) registry, diagnosed between 1991 and 2011, followed until 2014, were eligible for this study.Early IMM exposure was defined as having a first thiopurine prescription within 6 months after diagnosis with a treatment duration of at least 3 months.The long-term outcome was studied in terms of CD-related hospitalisation, corticosteroid use, surgery, and the development of strictures or fistulas.To avoid immune-time bias, the first year after diagnosis, including possible events, was censored in all patients.Kaplan-Meier survival analyses were used to determine the unadjusted cumulative probability of an event, and Cox regression modelling was applied to study the association between early IMM use and outcomes, adjusting for confounding by indication of early IMM use by propensity score adjustment.Data were presented as adjusted hazard ratios (aHR) with 95% confidence intervals (95%CI).Results: In total, 1 104 CD patients were followed for more than 12 months.Of these, 223 (20.2%) had early IMM exposure, with an average treatment duration of 4.2 years (SD 3.2).In the group without early IMM exposure (n = 881, 79.7%), 51.0% commenced IMM therapy later in disease course, at an average of 3.4 years (SD 3.7) after diagnosis.The mean follow-up was 6.7 years (SD 3.9) and 9.8 years (SD 5.8) for the early IMM and no early IMM group, respectively.During follow-up, no significant differences were observed in the 10-year hospitalisation risk (28.6% vs 35.5%, aHR 0.78; 95% CI 0.55-1.10), the 10-year surgery risk (15.2% vs 17.4%, aHR 0.65; 95%CI 0.40-1.06),or the 10-year phenotype progression risk (24.1% vs 25.9%, aHR 0.87; 95% CI 0.55-1.38).In contrast, a reduction in the 10-year corticosteroid exposure risk (39.1% vs 45.0%, aHR 0.73; 95% CI 0.54-0.99)was found.Conclusions: In this population-based study, early immunomodulator exposure was associated with a decreased need for corticosteroids, whereas no benefit was observed on the risks of hospitalisation, surgery, or phenotype progression.These findings underline the complexity of changing the natural history of CD and warrants further research to identify the optimal treatment strategy.