Transmural cross-sectional findings and bowel damage assessment in preclinical Crohn's disease: a case-control study.

PURPOSE: Crohn's disease (CD) is a progressive disorder leading to cumulative bowel damage. The Lémann index is a validated tool that can help in monitoring the progression of the disease and evaluating the effectiveness of different therapies. Our aim was to describe the main radiological findings in incidentally diagnosed CD and to evaluate bowel damage in this subgroup compared to patients diagnosed at later stages. METHODS: Patients with an incidental diagnosis of CD during the colorectal cancer screening program were compared to controls with a CD cohort diagnosed after symptomatic onset and matched 1:1 by disease extent. All cross-sectional examinations were centrally read, performing a descriptive analysis of the main findings and calculation of Lémann index. RESULTS: Thirty-eight patients were included: 19 with preclinical CD (median age 55 years (IQR, 54-62), 53% male, 74% non-smokers; 74% B1 and 26% B2) and 19 matched-controls with symptomatic CD. In those with preclinical CD, the most frequent transmural findings on MRE were contrast enhancement (79%), wall thickening (79%), followed by lymphadenopathy (68%), edema (42%), and increased vascularity (42%). Among those with strictures, controls showed a higher rate of preestenotic dilation (100% vs. 0%, p = 0.01). Bowel damage assessment revealed no statistically significant differences in the Lémann index between preclinical CD and controls (p = 0.95). A statistically significant higher score in the colonic/rectum score was observed (p = 0.014). CONCLUSION: Patients with preclinical CD demonstrate similar radiological findings and degree of bowel damage as new-onset symptomatic CD.

Subclinical bowel inflammation increases healthcare resources utilization and steroid use before diagnosis of inflammatory bowel disease.

BACKGROUND: Previous data support that the inflammatory process underlying ulcerative colitis (UC) and Crohn's disease (CD) can start years before the diagnosis. The aim of this study was to determine if patients with an incidental diagnosis of UC or CD demonstrate an increase in healthcare utilization in the years preceding the symptomatic onset of the disease. METHODS: We performed a multicenter, retrospective, hospital-based, case-control study. Patients with an incidental diagnosis of UC or CD during the colorectal cancer screening program at 9 hospitals were included. Cases were matched 1:3 and compared separately with two control populations: one including healthy non-IBD subjects adjusted by gender, age, and date, excluding those with visits to Gastroenterology; and a second control cohort of UC/CD patients with symptomatic onset. RESULTS: A total of 124 patients with preclinical inflammatory bowel disease (IBD) were included (87 UC, 30 CD, 7 IBD unclassified; median age 56 years). Patients with preclinical IBD showed an increase in the number of visits to Primary Care up to 3 and 5 years before diagnosis (aIRR 1.59, 95% CI [1.37-1.86], p = 0.001; aIRR 1.43, 95% CI [1.24-1.67], p = 0.01) and more frequent use of steroids (aOR 2.84, 95% CI [1.21-6.69], p = 0.03; aOR 2.25, 95% CI [1.06-4.79], p = 0.04) compared to matched non-IBD healthy controls, respectively. In contrast, patients with a symptomatic onset visited Primary Care less frequently, but they had an increase in the number of visits to Emergency Department, specialist care, sick-leaves, CT/ultrasound examinations, and use of antibiotics or systemic steroids. CONCLUSIONS: There is an increased need for medical assistance and use of systemic steroids during the presymptomatic phase of IBD. These results will help in establishing new tools for early identification of IBD in the future.

Surgery due to Inflammatory Bowel Disease During Pregnancy: Mothers and Offspring Outcomes From an ECCO Confer Multicentre Case Series [Scar Study].

AIMS: i] To evaluate the evolution of pregnancies and offspring after inflammatory bowel disease [IBD] surgery during pregnancy; and ii] to describe the indications, the surgical techniques, and the frequency of caesarean section concomitant with surgery. METHODS: Patients operated on due to IBD during pregnancy after 1998 were included. Participating clinicians were asked to review their databases to identify cases. Data on patients' demographics, IBD characteristics, medical treatments, IBD activity, pregnancy outcomes, surgery, delivery, and foetal and maternal outcomes, were recorded. RESULTS: In all, 44 IBD patients were included, of whom 75% had Crohn's disease; 18% of the surgeries were performed in the first trimester, 55% in the second, and 27% in the third trimester. One patient had complications during surgery, and 27% had postsurgical complications. No patient died. Of deliveries, 70% were carried out by caesarean section. There were 40 newborns alive. There were four miscarriages/stillbirths [one in the first, two in the second, and one in the third trimester]; two occurred during surgery, and another two occurred 2 weeks after surgery; 14% of the surgeries during the second trimester and 64% of those in the third trimester ended up with a simultaneous caesarean section or vaginal delivery. Of the 40 newborns, 61% were premature and 47% had low birth weight; 42% of newborns needed hospitalisation [25% in the intensive care unit]. CONCLUSIONS: IBD surgery during pregnancy remains an extremely serious situation. Therefore, surgical management should be performed in a multidisciplinary team, involving gastroenterologists, colorectal surgeons, obstetricians, and neonatal specialists.

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.

Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease: A Multicentre Study of Geteccu.

BACKGROUND: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. AIMS: To evaluate the impact of biologics on the risk of PC. METHODS: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. RESULTS: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). CONCLUSIONS: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.

Antitumor Necrosis Factor Agents to Treat Endoscopic Postoperative Recurrence of Crohn's Disease: A Nationwide Study With Propensity-Matched Score Analysis.

INTRODUCTION: Patients with Crohn's disease experiencing endoscopic postoperative recurrence (POR) may benefit from antitumor necrosis factor (TNF) agents but scarce data on this are available. Our aim was to assess the efficacy of anti-TNF in improving mucosal lesions in patients with endoscopic POR. METHODS: Multicenter, retrospective, study of patients with Crohn's disease who underwent therapy with anti-TNF agents for endoscopic POR (Rutgeerts score > i1). Treatment outcomes were assessed by the findings in the last ileocolonoscopy performed after anti-TNF therapy was initiated. Endoscopic improvement and remission were defined as any reduction in the baseline Rutgeerts score and by a Rutgeerts score < i2, respectively. RESULTS: A total of 179 patients were included, 83 were treated with infliximab and 96 with adalimumab. Median time on anti-TNF therapy at the last endoscopic assessment was 31 months (interquartile range, 13-54). Endoscopic improvement was observed in 61%, including 42% who achieved endoscopic remission. Concomitant use of thiopurines and treatment with infliximab were associated with endoscopic improvement (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.04-4.46; P = 0.03, and OR 2.34, 95% CI 1.18-4.62; P < 0.01, respectively) and endoscopic remission (OR 3.16, 95% CI 1.65-6.05; P < 0.01, and OR 2.01, 95% CI 1.05-3.88; P = 0.04, respectively) in the multivariable logistic regression analysis. These results were confirmed in a propensity-matched score analysis. DISCUSSION: In patients with endoscopic POR, anti-TNF agents improve mucosal lesions in almost two-thirds of the patients. In this setting, concomitant use of thiopurines and use of infliximab seem to be more effective in improving mucosal lesions.

Adalimumab or Infliximab for the Prevention of Early Postoperative Recurrence of Crohn Disease: Results From the ENEIDA Registry.

BACKGROUND: Anti-tumor necrosis factor agents (anti-TNFs) are efficacious at preventing the postoperative recurrence (POR) of Crohn disease, as demonstrated in 2 randomized controlled trials. However, real-life data for infliximab or adalimumab in this setting are scarce. Our aim was to assess both the efficiency of anti-TNFs at preventing early POR of Crohn disease in clinical practice and the associated risk factors for POR. METHODS: Patients in whom anti-TNFs were prescribed for the prevention of POR within 3 months after ileocolonic resection and who had an endoscopic assessment within 18 months were identified from the ENEIDA registry. Clinical and endoscopic features were collected within 18 months after surgery. RESULTS: In total, 152 patients were included (55 treated with infliximab, 97 with adalimumab, and 39% with concomitant immunosuppressants). Anti-TNF treatment was started after a median time of 29 days (IQR 13-44) after surgery. Eighty-two percent of patients had at least one risk factor for POR, and 82% had been exposed to anti-TNFs before the index surgery. Overall, 34% had endoscopic POR (as defined using a Rutgeerts endoscopic score > i1); 14% had advanced endoscopic POR (>i2); and 20% had clinical POR, with no differences between infliximab and adalimumab. In the multivariate analysis, only perianal disease (odds ratio 2.73, 95% confidence interval [CI] 1.26-5.91) and rectal involvement (odds ratio 2.79, 95% CI 1.09-7.14) were independent predictors of endoscopic POR. CONCLUSIONS: In clinical practice, anti-TNFs for the prevention of POR of Crohn disease are frequently used in patients experienced with anti-TNFs and with concomitant immunosuppressants. The efficacy of infliximab and adalimumab for POR prevention is similar and in accordance with the results obtained in randomized controlled trials.

Adalimumab treatment of anti-TNF-naïve patients with ulcerative colitis: Deep remission and response factors.

BACKGROUND: Adalimumab is the second tumour necrosis factor antagonist (anti-TNF) adopted for the treatment of ulcerative colitis. Clinical data from naïve patients are scarce. AIM: Examine the response to adalimumab in TNF-antagonist-naïve patients. METHODS: This multicentre, observational, prospective study was conducted using a cohort of consecutive patients with ulcerative colitis. Clinical remission, mucosal healing and deep remission were examined employing the Mayo Score and Mayo Endoscopic Score. Clinical response was assessed using the Partial Mayo Score. RESULTS: Of 53 individuals included in this study, 49.1% of patients were in clinical remission at week 8 and 60.3%, at week 52. Clinical response was observed in 84.9% and 69.8%, respectively. Mucosal healing was found in 62.3% and 67.9% of the patients, and 43.4% and 58.4% showed deep remission at week 8 and 52, respectively. After a year, 71.7% of the patients continued the adalimumab treatment. Adverse effects were observed in 28.3% of patients. Multivariate analysis showed that the long-term factor predictive of response at week 52 was the response in week 8 (expressed as Mayo Score; OR 0.66; 95% IC 0.1-0.67, p < 0.006). CONCLUSIONS: Adalimumab treatment of ulcerative colitis is effective; the results are better in clinical practice and in patients naïve to anti-TNF.

Prevalence of Malnutrition and Nutritional Characteristics of Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: This study sought to determine the prevalence of malnutrition in patients with inflammatory bowel disease, to analyse the dietary beliefs and behaviours of these patients, to study their body composition, to evaluate their muscular strength and to identify the factors associated with malnutrition in these patients. METHODS: This was a prospective, multicentre study. Crohn's disease and ulcerative colitis patients from 30 Spanish centres, from the outpatient clinics, were included. A questionnaire of 11 items was applied to obtain data from patients' dietary behaviour and beliefs. Patients who accepted were evaluated to assess their nutritional status using Subjective Global Assessment and body mass index. Body composition was evaluated through bioelectrical impedance. RESULTS: A total of 1271 patients were included [51% women, median age 45 years, 60% Crohn's disease]. Of these, 333 patients underwent the nutritional evaluation. A total of 77% of patients declared that they avoided some foods to prevent disease relapse. Eighty-six per cent of patients avoided some foods when they had disease activity because of fear of worsening the flare. Sixty-seven per cent of patients modified their dietary habits after disease diagnosis. The prevalence of malnutrition was 16% [95% confidence interval = 12-20%]. In the multivariate analysis, history of abdominal surgery, active disease and avoidance of some foods during flares were associated with higher risk of malnutrition. CONCLUSIONS: The prevalence of malnutrition in inflammatory bowel disease patients was high. We identified some predictive factors of malnutrition. Most of the patients had self-imposed food restrictions, based on their beliefs.

Budd-Chiari syndrome secondary to inflammatory pseudotumor of the liver: Report of a case with a 10-year follow-up.

Inflammatory pseudotumor (IPT) of the liver is a rare benign tumor of unknown origin, it has the appearance of a malignant tumor but has a benign histology and clinical course. We report a case of a 63-year-old man diagnosed of IPT of the liver and followed for 10 years. During the clinical course, he developed a secondary Budd-Chiari syndrome, with a successful response to a transjugular intrahepatic portosystemic shunt over a 5-year follow-up period.

Steroid-refractory ulcerative colitis and associated primary sclerosing cholangitis treated with infliximab.

Primary sclerosing cholangitis is an infrequent extraintestinal manifestation of ulcerative colitis. Damage to bile ducts is irreversible and medical therapies to prevent progression of the disease are usually ineffective. We describe a patient with long-standing ulcerative colitis, which was refractory to corticosteroid therapy who developed primary sclerosing cholangitis (biochemical stage II/IV) in the course of his pancolitis. Treatment with infliximab (5 mg/kg as an induction dose followed by maintenance doses every two months) was indicated because of steroid-dependent disease associated to primary sclerosing cholangitis as well as sacroiliitis and uveitis and previous episode of severe azathioprine-related hepatic toxicity. At present, after two years of follow-up, the patient is asymptomatic with normal liver tests and complete resumption of daily life activities. This case draws attention to the usefulness of anti-tumor necrosis factor-alpha therapy for the management of primary sclerosing cholangitis as extraintestinal manifestation of inflammatory bowel disease.