Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study.

BACKGROUND: Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn's disease (CD) patients in real-world clinical practice. METHODS: A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. RESULTS: A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). CONCLUSIONS: Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.

This large retrospective study demonstrated the short- and long-term effectiveness and safety of ustekinumab in patients with Crohn's disease in real-world clinical practice, including those with refractory disease.

Perianal Crohn's disease: clinical implications, prognosis and use of resources.

OBJECTIVE: to investigate the prevalence of perianal disease, the associated phenotypical factors, its influence on prognosis and its impact on the use of health resources for patients with Crohn's disease. METHODS: a unicentric retrospective observational study was performed with 430 patients with Crohn's disease tracked through a monographical consultation of intestinal inflammatory disease. Demographic and phenotypical data of Crohn's disease, pharmacological and surgical treatments, complementary tests carried out and hospital admissions were analyzed. A comparative study between those patients without perianal disease and those with perianal disease was performed, both in simple form and complex form. RESULTS: the prevalence of perianal disease was 40.2 %, and fistulas and abscesses were the most frequent manifestations. These appearances were associated with an affected rectum and the existence of extra-intestinal manifestations. The patients with perianal disease most frequently required immuno-suppressant and biological treatment, but no further abdominal surgery. Amongst the patients with perianal disease, the need for biologics was more frequent for luminal disease (42.8 % vs 30.7 %). Furthermore, more explorations were needed, aimed at the study of perianal disease and recto-colonoscopies, although more magnetic resonance (MR)/computed tomography (CT) enterographies were not required. CONCLUSIONS: perianal disease has a high prevalence among patients with Crohn's disease, especially when the rectum is affected. It is associated with a worse prognosis and more frequently requires biological treatments due to perianal and luminal evolution, especially in cases of complex perianal disease. This condition calls for more hospital admissions and complementary tests.

Impact of Epstein-Barr virus infection on inflammatory bowel disease (IBD) clinical outcomes.

OBJECTIVE: to evaluate the role of Epstein-Barr virus (EBV) on the intestinal mucosa in the evolution of inflammatory bowel disease (IBD). The risk factors for EBV infection and the frequency of EBV-associated lymphoproliferative disorders in IBD patients were also investigated. METHODS: intestinal biopsies of IBD patients with available EBV status determined by Epstein-Barr-encoding RNA (EBER) in situ hybridization were identified in the Pathology Database of our center. Clinical information, including phenotypic characteristics of IBD, previous treatments, diagnosis of lymphoma and patient outcome were reviewed in all cases. RESULTS: fifty-six patients with IBD (28 Crohn's disease, 27 ulcerative colitis and one unclassified colitis) were included. EBV in intestinal mucosa was positive in 26 patients (46 %) and was associated to a lymphoproliferative syndrome in one case. EBV positivity was associated with severe histological activity (52 % vs 17.2 %; p 0.007), the presence of a lymphoplasmacytic infiltrate (50 % vs 33.3 %; p 0.03) and active steroid treatment (61.5 % vs 33.3 %; p 0.03). Multivariate analyses only found an association between EBV and lymphoplasmacytosis (p 0.001). Escalation in previous treatment was significantly more frequent in the EBER+ group (53.8 % vs 26.7 %; p 0.038). No cases developed lymphoma during follow-up. CONCLUSIONS: EBV on the intestinal mucosa is associated with a poor outcome of IBD and the need for escalation of therapy. Lymphoplasmacytic infiltrate is associated with EBV infection. EBER+ patients used steroids more frequently compared with EBER- patients. No EBER+ patients developed lymphoma during follow-up.

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study.

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery.

Megacolon in inflammatory bowel disease: response to infliximab.

Megacolon is a serious complication of inflammatory bowel disease that often requires a colectomy. Infliximab is a therapeutic alternative when conventional treatment fails, before resorting to surgery. Its use is currently based on the publication of isolated cases. We present a series of 12 patients with megacolon treated with infliximab, five with signs of systemic toxicity. Seventy-five percent of the patients avoided a colectomy during their acute episode after early infliximab treatment, 2.45 days after the megacolon diagnosis. There was a greater risk of surgery among patients with ulcerative colitis and toxicity criteria. Two more patients required follow-up surgery despite long-term infliximab treatment. No patient suffered significant treatment-related adverse effects or significant post-surgery complications.

Pancreatobiliary maljunction: association with gallbladder cancer.

BACKGROUND: Pancreatobiliary maljunction is a rare disease characterized by the junction of the pancreatic and biliary ducts outside of the duodenal wall, which normally results in a large common duct. As a result, there is a greater risk of acute pancreatitis and cancer of the gallbladder and biliary tract. CASE REPORT: We present the case of a 43-year-old female diagnosed with a pancreatobiliary maljunction and an associated stenosis of the bile duct, secondary to an episode of acute pancreatitis. She underwent several endoscopic retrograde cholangiopancreatography procedures over the course of three years, without improvement of the stenosis, and therefore a surgical approach was taken. Prior to the surgical intervention, magnetic resonance imaging showed the presence of an 11-mm polyp in the gallbladder. A histological study of the surgical sample identified intramucosal adenocarcinoma over a tubular adenoma of the gallbladder. DISCUSSION: Pancreatobiliary maljunction can be considered as a premalignant entity due to the risk of developing cancer of the biliary tree and gallbladder. Therefore, these patients should undergo a prophylactic intervention, despite being asymptomatic.

Hemosuccus pancreaticus secondary to pseudoaneurysm of the splenic artery.

A 41-years-old male who presents abdominal pain and rectal bleeding with acute anemization. Both the gastroscopy and the colonoscopy dont identify any potential cause of bleeding. The computed tomography (CT) shows a pseudoaneurysm of the splenic artery. Gastrointestinal bleeding was attributed to a hemosuccus pancreaticus secondary to the pseudoaneurysm of the splenic artery. An arteriography was performed to embolize it. Pseudoaneurysm of the splenic artery is a rare cause of gastrointestinal bleeding. Given the risk of a rupture, the treatment is mandatory irrespective of the size or symptoms.