Long-term, Real-life, Observational Study in Treating Outpatient Ulcerative Colitis with Golimumab

Background and Aims: Several studies have found Golimumab (GOL) effective and safe in the short-term treatment of ulcerative colitis (UC), but few long-term data are currently available from real world. Our aim was to assess the long-term real-life efficacy and safety of GOL in managing UC outpatients in Italy. Methods: A retrospective multicenter study assessing consecutive UC outpatients treated with GOL for at least 3-month of follow-up was made. Primary endpoints were the induction and maintenance of remission in UC, defined as Mayo score ≤2. Several secondary endpoints, including clinical response, colectomy rate, steroid free remission and mucosal healing, were also assessed during the follow-up. Results: One hundred and seventy-eight patients were enrolled and followed up for a median (IQR) time of 9 (3-18) months (mean time follow-up: 33.1±13 months). Clinical remission was achieved in 57 (32.1%) patients: these patients continued with GOL, but only 6 patients (3.4%) were still under clinical remission with GOL at the 42nd month of follow-up. Clinical response occurred in 64 (36.4%) patients; colectomy was performed in 8 (7.8%) patients, all of them having primary failure. Steroid-free remission occurred in 23 (12.9%) patients, and mucosal healing was achieved in 29/89 (32.6%) patients. Adverse events occurred in 14 (7.9%) patients. Conclusions: Golimumab does not seem able to maintain long-term remission in UC in real life. The safety profile was good

Treatment of Crohn’s disease with colony-stimulating factors: An overview

Luisa Guidi1, Giammarco Mocci1, Manuela Marzo1, Sergio Rutella21Department of Internal Medicine, Operative Unit of Gastroenterology, and 2Department of Hematology, Laboratory of Immunology, Università Cattolica del Sacro Cuore, Rome, ItalyAbstract: Current treatments for Crohn’s disease are aimed at suppressing excessive immune activation in the bowel walls. However, alternative strategies can be drawn. These involve the augmentation of the innate immune response, in the hypothesis that patients affected with Crohn’s disease are characterized by a relative immunodeficiency, with failure of the defensive barrier to luminal microbes and microbial products, resulting in a chronic inflammatory process sustained by T-cells. Alternatively, therapy could act by enhancing the number or the activity of subpopulations of T regulatory cells, able to reduce T-cell activation. Colony-stimulating factors are substances that could be efficacious in these settings. In fact, besides in vitro and animal studies, some human studies have been conducted in recent years with both granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor, the results of which are reported here.Keywords: inflammatory bowel disease, Crohn’s disease treatment, G-CSF, GM-CS

Review article: safety of new biologic agents for inflammatory bowel disease in the liver

New biologic agents (vedolizumab, ustekinumab and tofacitinib) represent an effective treatment for inflammatory bowel diseases and have been recently approved. However, with a rapidly evolving complement of advanced targeted therapies, new concerns about their potentially undesirable effects on liver function emerge. In particular, little is known about safety data in patients with hepatitis B virus, hepatitis C virus chronic infections, cirrhosis and in transplanted patients who are accumulating. In addition, these new agents have also been associated with drug-induced liver injury. Limited data on the efficacy of vedolizumab in patients with primary sclerosing cholangitis are also available. This article reviews available data about hepatic safety concerns in patients receiving vedolizumab, ustekinumab and tofacitinib with and without preexistent hepatic diseases

Insights into Mesalazine Use in Clinical Practice of Young Gastroenterologists

Background: Mesalazine is among the medications most prescribed by gastroenterologists, with variable and controversial use in different settings. We aimed to explore the use of mesalazine in the clinical practice of young gastroenterologists. Methods: A web-based electronic survey was distributed to all participants of the National Meeting of the Italian Young Gastroenterologist and Endoscopist Association. Results: A total of 101 participants took part in the survey, with a majority (54.4%) being aged >30 years, 63.4% of whom were trainees in academic hospitals, and 69.3% of whom were involved in the clinical management of inflammatory bowel disease (IBD). While both non-dedicated and IBD physicians generally agreed on the appropriate dose of mesalazine for mild ulcerative colitis (UC), significant differences were observed between the two groups for moderate-severe ulcerative colitis (UC). Additionally, in IBD patients who were starting immuno-modulators and/or biologics, 80% of IBD-dedicated physicians continued to prescribe mesalazine, compared to 45.2% of non-dedicated physicians (p = 0.002). Indeed, 48.4% of non-dedicated IBD physicians did not acknowledge mesalazine for colorectal cancer chemoprevention. With regards to Crohn's disease, it is mainly used by 30.1% of IBD physicians for preventing postoperative recurrence of Crohn's disease. Finally, 57.4% used mesalazine for symptomatic uncomplicated diverticular disease, and 84.2% did not recommend its use for irritable bowel syndrome. Conclusions: This survey showed heterogeneous behaviors in the daily use of mesalazine, mainly in the management of IBD. Educational programs and novel studies are needed to clarify its use

Ustekinumab in the Treatment of Inflammatory Bowel Diseases: Evolving Paradigms

Inflammatory bowel diseases, comprising Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing, and remitting immune-mediated inflammatory diseases affecting the gastrointestinal tract. Ustekinumab (UST) is a monoclonal antibody that blocks the p40 subunit of the anti-interleukin (IL) 12/23. Pivotal trials (CERTIFI and UNITI-IM for CD, UNIFI for UC) established the efficacy of UST for the induction and maintenance of remission in both CD and UC, with the most favorable results in naïve patients to biologics. In recent years, a wealth of ‘real-world’ data has emerged supporting positive clinical, endoscopic, and histological outcomes in patients treated with UST, as well as reassuring safety data. More recently, the results of the first head-to-head trials of UST and tumor necrosis factor (TNF) antagonists were reported. Moreover, a number of studies exploring the role of UST in specific clinical settings, such as perianal CD, postoperative complications and recurrence, extraintestinal manifestations, chronic antibiotic-refractory pouchitis, and pregnancy, were reported. This review explores the results reported to date on UST, including those from pivotal trials, real-world data, and emerging studies regarding therapeutic drug monitoring and immunogenicity. The safety profile of UST was also reviewed

Management of perianal fistulas in Crohn's disease: an up-to-date review

Perianal disease is one of the most disabling manifestations of Crohn's disease. A multidisciplinary approach of gastroenterologist, colorectal surgeon and radiologist is necessary for its management. A correct diagnosis, based on endoscopy, magnetic resonance imaging, endoanal ultrasound and examination under anesthesia, is crucial for perianal fistula treatment. Available medical and surgical therapies are discussed in this review, including new local treatment modalities that are under investigatio