Crohn's disease after surgery: Changes in post-operative management strategies over time and their impact on long-term re-operation rate-A retrospective multicentre real-world study.

BACKGROUND: Few data are available addressing the impact of post-operative management of Crohn's disease (CD) on long-term clinical course. AIM: To assess the evolution of post-operative management strategies over the last 40 years and their impact on the re-operation rate of CD. METHODS: We included 657 patients with CD who had undergone their first radical ileo-caecal resection between 1980 and 2020. Three cohorts were defined according to year of surgery: cohort 1 (1980-1998; n = 198), cohort 2 (1999-2009; n = 218) and cohort 3 (2010-2020; n = 241). We estimated exposure to immunomodulators and anti-TNFα agents after surgery and rates of re-operation using Kaplan-Meier survival analyses. We used Cox proportional hazards regression to assess the association of clinical variables with time to re-operation. RESULTS: Immunosuppressants, (IMMs) and anti-TNFα exposure within 5 years after surgery increased significantly from cohort 1 to cohort 2 and cohort 3 (IMMs: 1.6%, 38.2% and 28.0%, respectively, p < 0.001; anti-TNFα: 0.0%, 20.7% and 52.0%, respectively, p < 0.001). There was no significant difference across cohorts regarding the cumulative probability of re-operation within 5 and 10 years. Multivariate analysis identified IMMs/anti-TNFα exposure before the first surgery (HR 9.15; 95% CI 2.77-30.21) and post-operatively (HR: 0.24; 95% CI 0.07-0.74) as variables associated with the risk of re-operation. However, these associations had a time-varying effect and become non-significant after 5 and 2 years after surgery, respectively. CONCLUSION: Despite increased post-operative use of IMMs and anti-TNFα agents in the last two decades, the impact of these strategies on the risk of long-term re-operation rate has been modest.

Effect of Tofacitinib on One-Year Colectomy Risk in Anti-TNF Refractory Ulcerative Colitis: A Prospective Multicenter Italian Study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC). AIMS: Considering the number of anti-TNF non-responders, this study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52 weeks. METHODS: From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events. RESULTS: We included 58 patients with UC with an age of 42 ± 14.4 years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10 mg bid at W8 (p = 0.023) and W24 (p = 0.004), and with a higher partial Mayo score at W8 (p = 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation. CONCLUSIONS: In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52 weeks with a good safety profile.

Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease.

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

Effectiveness and safety of vedolizumab in a matched cohort of elderly and nonelderly patients with inflammatory bowel disease: the IG-IBD LIVE study.

BACKGROUND: Vedolizumab registration trials were the first to include elderly patients with moderate-to-severe ulcerative colitis (UC) or Crohn's disease (CD), but few real-life data have been reported in this population. AIMS: We investigated the effectiveness and safety of vedolizumab in matched cohorts of elderly and nonelderly UC and CD patients. METHODS: The Long-term Italian Vedolizumab Effectiveness (LIVE) study is a retrospective-prospective study including UC and CD patients who started vedolizumab from April 2016 to June 2017. Elderly patients (≥65 years) were matched clinically 1:2 to nonelderly patients (18-64 years); the 2 groups were followed until drug discontinuation or June 2019. RESULTS: The study included 198 elderly (108 UC, 90 CD) and 396 matched nonelderly patients (205 UC, 191 CD). Nonelderly UC patients had a significantly higher persistence on vedolizumab compared to elderly patients (67.6% vs. 51.4%, p = 0.02). No significant difference in effectiveness was observed between elderly and nonelderly CD patients (59.4% vs. 52.4%, p = 0.32). Age ≥65 years was associated with lower persistence in UC; for CD, previous exposure to anti-TNF-α agents, Charlson comorbidity index >2 and moderate-to-severe clinical activity at baseline were associated with lower persistence. There were recorded 130 adverse events, with comparable rates between the two groups. A Charlson comorbidity index >2 was associated with an increased risk of adverse events. CONCLUSION: Vedolizumab can be considered a safe option in elderly IBD patients. Its effectiveness in elderly UC patients may be reduced, while no age-dependent effect on effectiveness was observed in CD.

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.

Incident Colorectal Cancer in Inflammatory Bowel Disease.

Colorectal cancer (CRC) risk is increased in Inflammatory Bowel Disease (IBD) and surveillance needs to be tailored according to individual risk. The open issues include the role of the characteristics of IBD and CRC in determining the long-term outcome. These issues were assessed in our multicenter study, including a cohort of 56 IBD patients with incident CRC. The clinical and histopathological features of IBD patients and of CRC were recorded. Incident CRC in IBD occurred at a young age (≤40 years) in 25% of patients (median age 55.5 (22-76)). Mucinous signet-ring carcinoma was detected in 6 out of the 56 (10.7%) patients, including 4 with Ulcerative Colitis (UC) and 2 with Crohn's disease (CD). CRC was more frequently diagnosed by colonoscopy in UC (85.4% vs. 50%; p = 0.01) and by imaging in Crohn's Disease CD (5.8% vs. 31.8%; p = 0.02). At onset, CRC-related symptoms occurred in 29 (51.9%) IBD patients. The time interval from the diagnosis of IBD to CRC was shorter in UC and CD patients with >40 years (p = 0.002; p = 0.01). CRC-related death occurred in 10 (29.4%) UC and in 6 (27.2%) CD patients (p = 0.89), with a short time interval from CRC to death (UC vs. CD: 6.5 (1-68) vs. 14.5 (8-40); p = 0.85; IBD: 12 months (1-68)). CRC occurring at a young age, a short time interval from the diagnosis of IBD to CRC-related death in the elderly, CRC-symptoms often mimicking IBD relapse and the observed high mortality rate may support the need of closer surveillance intervals in subgroups of patients.

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.

Female reproductive health and inflammatory bowel disease: A practice-based review.

Inflammatory bowel diseases, namely ulcerative colitis and Crohn's disease, occur worldwide and affect people of all ages, with a high impact on their quality of life. Sex differences in incidence and prevalence have been reported, and there are also gender-specific issues that physicians should recognize. For women, there are multiple, important concerns regarding issues of body image and sexuality, menstruation, contraception, fertility, pregnancy, breastfeeding and menopause. This practice-based review focuses on the main themes that run through the life of women with inflammatory bowel diseases from puberty to menopause. Gastroenterologists who specialize in inflammatory bowel diseases and other physicians who see female patients with inflammatory bowel diseases should provide support for these problems and offer adequate therapy to ensure that their patients achieve the same overall well-being and health as do women without inflammatory bowel diseases.

Vitamin D Signaling in Gastro-Rheumatology: From Immuno-Modulation to Potential Clinical Applications.

In the last decades, the comprehension of the pathophysiology of bone metabolism and its interconnections with multiple homeostatic processes has been consistently expanded. The branch of osteoimmunology specifically investigating the link between bone and immune system has been developed. Among molecular mediators potentially relevant in this field, vitamin D has been recently pointed out, and abnormalities of the vitamin D axis have been described in both in vitro and in vivo models of inflammatory bowel diseases (IBD) and arthritis. Furthermore, vitamin D deficiency has been reported in patients affected by IBD and chronic inflammatory arthritis, thus suggesting the intriguing possibility of impacting the disease activity by the administration vitamin D supplements. In the present review, the complex interwoven link between vitamin D signaling, gut barrier integrity, microbiota composition, and the immune system was examined. Potential clinical application exploiting vitamin D pathway in the context of IBD and arthritis is presented and critically discussed. A more detailed comprehension of the vitamin D effects and interactions at molecular level would allow one to achieve a novel therapeutic approach in gastro-rheumatologic inflammatory diseases through the design of specific trials and the optimization of treatment protocols.

Why Do Immunosuppressed Patients with Inflammatory Bowel Disease Not Seem to Be at a Higher Risk of COVID-19?

The COVID-19 pandemic has created a public health emergency. In this context, there are major concerns for patients with inflammatory bowel disease (IBD), particularly for those treated with immunomodulators, biologics, and Janus Kinase inhibitors. Infection susceptibility is, in fact, one of the reported risks for immunotherapy drugs. This review provides the existing evidence from worldwide case series describing: (a) the risk for the SARS-CoV-2 infection and (b) the risk of a severe infection outcome in patients with IBD treated with immunotherapy. Further, the review discusses the potential mechanisms underlying why this group of patients with IBD might be protected from contracting the infection and from a worse disease. From the available data, it appears that these patients should have an enhanced adherence to the recommended preventive measures, suggesting a role in reducing their risk of infection. Furthermore, the immunotherapy may dampen the cytokine storm and inflammation associated with COVID-19. The results of this review seem to confirm that patients with IBD receiving immunomodulators, biologics, or Janus Kinase inhibitors do not have an increased risk of contracting SARS-CoV-2 infection or develop a more severe COVID-19. According to the current evidence, it is advisable to maintain immunotherapy, apart from corticosteroids, in patients with IBD in order to avoid relapse. This review reports only on the cases of patients who tested positive for SARS-CoV-2 by RT-PCR of a nasopharyngeal swab sample. This is a limitation and a more accurate epidemiological picture of the infection will be obtained only via the expanded use of antibody tests.

Ustekinumab for treating ulcerative colitis: an expert opinion.

INTRODUCTION: Biologic agents have revolutionized the therapeutic management of ulcerative colitis. Anti-tumor necrosis factor agents were the first biologic drugs used to induce and maintain remission in this inflammatory bowel disease. Recently, another biologic option, ustekinumab, has become available for the treatment of moderate-to-severe ulcerative colitis. AREAS COVERED: In this article, the authors review the literature on the efficacy and safety of ustekinumab in the context of current biologic agents used for the management of this disease. The potential role of ustekinumab in the treatment paradigm of the disease is also discussed. Expert opinion: The UNIFI trial has demonstrated the efficacy and safety of ustekinumab in induction and maintenance phases of treatment for ulcerative colitis. Ustekinumab may provide clinical benefit in a range of settings in patients with ulcerative colitis, even for those with multiple treatment failures, which are relatively common in daily clinical practice. Future clinical trials should compare the efficacy of ustekinumab with existing biologic agents in the management of ulcerative colitis.

Cancer Risk in Inflammatory Bowel Disease: A 6-Year Prospective Multicenter Nested Case-Control IG-IBD Study.

BACKGROUND: In a 6-year, multicenter, prospective nested case-control study, we aimed to evaluate risk factors for incident cancer in inflammatory bowel disease (IBD), when considering clinical characteristics of IBD and immunomodulator use. The secondary end point was to provide characterization of incident cancer types. METHODS: All incident cases of cancer occurring in IBD patients from December 2011-2017 were prospectively recorded in 16 Italian Group for the Study of Inflammatory Bowel Disease units. Each of the IBD patients with a new diagnosis of cancer was matched with 2 IBD patients without cancer, according to IBD phenotype (ulcerative colitis [UC] vs Crohn's disease [CD]), age (±5 years), sex. Risk factors were assessed by multivariate logistic regression analysis. RESULTS: Cancer occurred in 403 IBD patients: 204 CD (CD cases), 199 UC (UC cases). The study population included 1209 patients (403 IBD cases, 806 IBD controls). Cancer (n = 403) more frequently involved the digestive system (DS; 32%), followed by skin (14.9%), urinary tract (9.7%), lung (6.9%), genital tract (6.5%), breast (5.5%), thyroid (1.9%), lymphoma (2.7%, only in CD), adenocarcinoma of the small bowel (SBA; 3.9%, 15 CD, 1 pouch in UC), other cancers (15.9%). Among cancers of the DS, colorectal cancer (CRC) more frequently occurred in UC (29% vs 17%; P < 0.005), whereas SBA more frequently occurred in CD (13% vs 6.3% P = 0.039). In CD, perforating (B3) vs non-stricturing non-perforating (B1) behavior represented the only risk factor for any cancer (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.33-4.11). In CD, risk factors for extracolonic cancer (ECC) were a B3 vs B1 and a stricturing (B2) vs B1 behavior (OR, 2.95; 95% CI, 1.62-5.43; OR, 1.79; 95% CI, 1.09-2.98). In UC, risk factors for ECC and for overall cancer were abdominal surgery for UC (OR, 4.63; 95% CI, 2.62-8.42; OR, 3.34; 95% CI, 1.88-5.92) and extensive vs distal UC (OR, 1.73; 95% CI, 1.10-2.75; OR, 1.99; 95% CI, 1.16-3.47). Another risk factor for ECC was left-sided vs distal UC (OR, 1.68; 95% CI, 1.00-2.86). Inflammatory bowel disease duration was a risk factor for skin and urinary tract cancers. CONCLUSIONS: Perforating CD, extensive UC, and abdominal surgery for UC were identified as risk factors for overall incident cancer and for ECC. The clinical characteristics associated with severe IBD may increase cancer risk.

Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study.

BACKGROUND: The infliximab biosimilar CT-P13 was approved for use in Crohn's disease after clinical comparison with originator infliximab in ankylosing spondylitis and rheumatoid arthritis; however, concerns about such indication extrapolation have been expressed. This study investigated whether CT-P13 is non-inferior to infliximab in patients with Crohn's disease who were naive to biological therapy. METHODS: In this randomised, multicentre, double-blind, phase 3 non-inferiority study, we enrolled patients with active Crohn's disease who had not responded to, or were intolerant to, non-biological treatments. Patients were randomly assigned (1:1:1:1) to receive CT-P13 then CT-P13, CT-P13 then infliximab, infliximab then infliximab, or infliximab then CT-P13, with switching occurring at week 30. Patients received 5 mg/kg CT-P13 or infliximab at weeks 0, 2, 6, and then every 8 weeks up to week 54. The primary endpoint was the proportion of patients with a decrease of 70 points or more in Crohn's Disease Activity Index (CDAI) from baseline to week 6. A non-inferiority margin of -20% was set (CT-P13 was non-inferior to infliximab if the lower limit of the two-sided 95% CI for the treatment difference was greater than -20). This trial is registered with ClinicalTrials.gov, number NCT02096861, and is completed. FINDINGS: Between Aug 20, 2014, and Feb 15, 2017, 308 patients were assessed for eligibility, and 220 patients were enrolled: 111 were randomly assigned to initiate CT-P13 (56 to the CT-P13-CT-P13 group and 55 to the CT-P13-infliximab group) and 109 to initiate infliximab (54 to the infliximab-infliximab group and 55 to the infliximab-CT-P13 group). CDAI-70 response rates at week 6 were similar for CT-P13 (77 [69·4%, 95% CI 59·9 to 77·8] of 111) and infliximab (81 [74·3%, 95% CI 65·1 to 82·2] of 109; difference -4·9% [95% CI -16·9 to 7·3]), thereby establishing non-inferiority. Over the total study period, 147 (67%) patients experienced at least one treatment-emergent adverse event (36 [64%] in the CT-P13-CT-P13 group, 34 [62%] in the CT-P13-infliximab group, 37 [69%] in the infliximab-infliximab group, and 40 [73%] in the infliximab-CT-P13 group). INTERPRETATION: This study showed non-inferiority of CT-P13 to infliximab in patients with active Crohn's disease. Biosimilar CT-P13 could be a new option for the treatment of active Crohn's disease. FUNDING: Celltrion, Pfizer.

Sex Differences in Response to TNF-Inhibiting Drugs in Patients With Spondyloarthropathies or Inflammatory Bowel Diseases.

Spondyloarthritis (SpA) and inflammatory bowel diseases (IBD) are chronic inflammatory diseases characterized by an aberrant immune response and inflammation with a key role for TNF in their pathogenesis. Accordingly, TNF-inhibiting therapy (TNFi) has dramatically improved the management of these diseases. However, about 30% of patients discontinue TNFi for lack of response, loss of response, and side effects and/or adverse events. Thus, the possibility to identify in advance those patients who will have a good response to TNFi would be extremely beneficial. The aim of this study was to investigate differences between males and females with either SpA or IBD in response to TNFi molecules, i.e., infliximab (IFX) and adalimumab (ADA), considering the reasons for TNFi withdraw. Data of 594 patients, 349 with IBD (M/F: 194/155) and 245 with SpA (M/F: 123/122), previously unexposed to TNFi, were collected. In the IBD group, the rate of female patients discontinuing ADA was significantly higher than that of male patients (p = 0.03). No difference emerged according to the distribution of reason for discontinuation. Otherwise, a similar discontinuation rate between female and male patients receiving IFX therapy was observed. In the SpA group, the overall discontinuation rate was not different between males and females both for ADA and IFX. However, in patients treated with ADA, males interrupted therapy more frequently than females due to lack of response (p = 0.03). In conclusion, the assessment of sex differences in TNFi response could help physicians personalize the therapeutic approach in a sex-oriented perspective.

Management of ulcerative colitis in a real-life setting: An Italian multicenter, prospective, observational AIGO study.

BACKGROUND: No data are available on the variability in the clinical management of ulcerative colitis (UC) patients by Italian gastroenterologists. Therefore, improving the standards of UC care as provided by the National Welfare Clinical Path (PDTA), in accordance with the European Crohn's and Colitis Organization (ECCO) guidelines for UC, is not easy. AIMS: To assess the management of UC by Italian gastroenterologists in a real-life setting taking into account its variability. METHODS: This prospective, cross-sectional, observational study included IBD-specialized gastroenterologists (GSIBDs) and general gastroenterologists (GGs) working in Italian public hospital units. Consecutive patients with an UC flare were enrolled and the medical treatment evaluated. For each center, the physician in charge of the study (16 GSIBDs and 10 GGs) was administered two electronic questionnaires. RESULTS: Among 26 units, 573 UC patients were enrolled. Good adherence to the European guidelines was reported; GSIBDs reported greater adherence than GGs with a higher prescription of rectal and combination therapy in mild to moderate distal disease and a higher rate of hospitalization in severe UC. CONCLUSION: The management of UC by Italian gastroenterologists in clinical practice is good according to the ECCO consensus recommendations, though some discrepancies are present between GSIBDs and GGs.

Sustained Clinical Efficacy and Mucosal Healing of Thiopurine Maintenance Treatment in Ulcerative Colitis: A Real-Life Study.

BACKGROUND AND AIMS: Thiopurines are commonly used for treating ulcerative colitis (UC), despite the fact that controlled evidence supporting their efficacy is limited. The aim of this study was to evaluate the long-term outcome of thiopurines as maintenance therapy in a large cohort of UC patients. METHODS: All UC patients receiving thiopurine monotherapy at three tertiary IBD centers from 1995 to 2015 were identified. The primary endpoint was steroid-free clinical remission. Secondary endpoints were mucosal healing (MH), defined as Mayo endoscopic subscore 0, long-term safety, and predictors of sustained clinical remission. RESULTS: We identified 192 patients, contributing a total of 747 person-years of follow-up (median follow-up 36 months, range 1-210 months). Steroid dependency was the most common indication for thiopurine treatment (58%). Steroid-free remission occurred in 45.3% of patients; 36.3% stopped thiopurines because of treatment failure and 18.2% for adverse events or intolerance. The cumulative probability of maintaining steroid-free remission while on thiopurine treatment was 87%, 76%, 67.6%, and 53.4% at 12, 24, 36, and 60 months, respectively. MH occurred in 57.9% of patients after a median of 18 months (range 5-96). No independent predictors of sustained clinical remission could be identified. CONCLUSIONS: Thiopurines represent an effective and safe long-term maintenance therapy for UC patients.

Vedolizumab for inflammatory bowel disease: From randomized controlled trials to real-life evidence.

The biologic antitumor necrosis factor alpha (anti-TNFα) agents have revolutionised the treatment of inflammatory bowel disease (IBD). However, some patients experience primary nonresponse, loss of response, or intolerance. Therefore, introducing a newer class of therapy with a mechanism of action that acts on different inflammatory pathways involved in IBD pathogenesis is appealing. Vedolizumab is a fully humanised monoclonal antibody that selectively targets α4ß7 integrin. Based on the results of the pivotal clinical GEMINI trials, vedolizumab was approved for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD) refractory or intolerant to either conventional therapy or TNFα inhibitors. This review describes the efficacy, safety, and tolerability of vedolizumab reported in both randomized, controlled, clinical trials and from real-world experience in patients with UC and CD in order to identify its place in treatment algorithms for IBD.

Ustekinumab in the management of Crohn's disease: Expert opinion.

This expert-opinion paper reviews available evidence for the use of ustekinumab, a human interleukin 12/23 monoclonal antibody, in the treatment of Crohn's disease and discusses its potential role in the current treatment scenario for the condition. Ustekinumab appears to be associated with rapid and sustained clinical effect, as reported from the clinical research program, with additional support for potential mucosal healing. These characteristics are paralleled by a favorable safety profile, lack of immunogenicity and the presence of systemic anti-inflammatory activity. Importantly, ustekinumab requires only one single intravenous administration, while subsequent dosing is administered subcutaneously, with potential advantages for home-based therapy. Lastly, the dosage of ustekinumab is flexible. On the basis of the evidence, ustekinumab has a role in patients with primary failure or secondary loss of response to anti-tumor necrosis factor agents, as well as in those who have adverse events on front-line biologics or are reinitiating therapy after a treatment holiday. Current evidence suggests that ustekinumab may be particularly suitable in patients who present extra-intestinal manifestations of the disease or are at risk of infections. Ustekinumab may also be considered in the first-line setting, especially in frail patients, in young subjects or in those who have concomitant immune-mediated diseases.

Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD).

Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohn's disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohn's disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group.