Recommendations on the management of severe obesity in patients with inflammatory bowel disease of the Spanish Group on Crohn's Disease and Ulcerative Colitis (GETECCU), Spanish Society of Obesity (SEEDO), Spanish Association of Surgery (AEC) and Spanish Society of Digestive Endoscopy (SEED). / Recomendaciones sobre el manejo de la obesidad grave en pacientes con enfermedad inflamatoria intestinal del Grupo Español de Trabajo en Enfermedad Inflamatoria Intestinal (GETECCU), Sociedad Española de Obesidad (SEEDO), Asociación Española de Cirugía (AEC) y Sociedad Española de Endoscopia Digestiva (SEED).

Obesity is a multifactorial, chronic, progressive and recurrent disease considered a public health issue worldwide and an important determinant of disability and death. In Spain, its current prevalence in the adult population is about 24% and an estimated prevalence in 2035 of 37%. Obesity increases the probability of several diseases linked to higher mortality such as diabetes, cardiovascular disease, hyperlipidemia, arterial hypertension, non-alcoholic fatty liver disease, several types of cancer, or obstructive sleep apnea. On the other hand, although the incidence of inflammatory bowel disease (IBD) is stabilizing in Western countries, its prevalence already exceeds 0.3%. Paralleling to general population, the current prevalence of obesity in adult patients with IBD is estimated at 15-40%. Obesity in patients with IBD could entail, in addition to its already known impact on disability and mortality, a worse evolution of the IBD itself and a worse response to treatments. The aim of this document, performed in collaboration by four scientific societies involved in the clinical care of severe obesity and IBD, is to establish clear and concise recommendations on the therapeutic possibilities of severe or typeIII obesity in patients with IBD. The document establishes general recommendations on dietary, pharmacological, endoscopic, and surgical treatment of severe obesity in patients with IBD, as well as pre- and post-treatment evaluation.

Benefits of Paediatric to Adult Transition Programme in Inflammatory Bowel Disease: The BUTTERFLY Study of GETECCU and SEGHNP.

(1) Background: Transition is a planned movement of paediatric patients to adult healthcare systems, and its implementation is not yet established in all inflammatory bowel disease (IBD) units. The aim of the study was to evaluate the impact of transition on IBD outcomes. (2) Methods: Multicentre, retrospective and observational study of IBD paediatric patients transferred to an adult IBD unit between 2017-2020. Two groups were compared: transition (≥1 joint visit involving the gastroenterologist, the paediatrician, a programme coordinator, the parents and the patient) and no-transition. Outcomes within one year after transfer were analysed. The main variable was poor clinical outcome (IBD flare, hospitalisation, surgery or any change in the treatment because of a flare). Predictive factors of poor clinical outcome were identified with multivariable analysis. (3) Results: A total of 278 patients from 34 Spanish hospitals were included. One hundred eighty-five patients (67%) from twenty-two hospitals (65%) performed a structured transition. Eighty-nine patients had poor clinical outcome at one year after transfer: 27% in the transition and 43% in the no-transition group (p = 0.005). One year after transfer, no-transition patients were more likely to have a flare (36% vs. 22%; p = 0.018) and reported more hospitalisations (10% vs. 3%; p = 0.025). The lack of transition, as well as parameters at transfer, including IBD activity, body mass index < 18.5 and corticosteroid treatment, were associated with poor clinical outcome. One patient in the transition group (0.4%) was lost to follow-up. (4) Conclusion: Transition care programmes improve patients' outcomes after the transfer from paediatric to adult IBD units. Active IBD at transfer impairs outcomes.

Serum Levels of Lipoprotein Lipase Are Increased in Patients with Inflammatory Bowel Disease.

Disruption of the lipid profile is commonly found in patients with inflammatory bowel disease (IBD). Lipoprotein lipase (LPL) is a key molecule involved in triglyceride metabolism that plays a significant role in the progression of atherosclerosis. In this study, our aim was to study whether serum LPL levels are different in IBD patients and controls and whether IBD features are related to LPL. This was a cross-sectional study that encompassed 405 individuals; 197 IBD patients with a median disease duration of 12 years and 208 age- and sex-matched controls. LPL levels and a complete lipid profile were assessed in all individuals. A multivariable analysis was performed to determine whether LPL serum levels were altered in IBD and to study their relationship with IBD characteristics. After the fully multivariable analysis, including cardiovascular risk factors and the changes in lipid profile that the disease causes itself, patients with IBD showed significantly higher levels of circulating LPL (beta coefficient 196 (95% confidence interval from 113 to 259) ng/mL, p < 0.001). LPL serum levels did not differ between Crohn's disease and ulcerative colitis. However, serum C-reactive protein levels, disease duration, and the presence of an ileocolonic Crohn's disease phenotype were found to be significantly and independently positively related to LPL. In contrast, LPL was not associated with subclinical carotid atherosclerosis. In conclusion, serum LPL levels were independently upregulated in patients with IBD. Inflammatory markers, disease duration and disease phenotype were responsible for this upregulation.

Ustekinumab and vedolizumab for the prevention of postoperative recurrence of Crohn's disease: Results from the ENEIDA registry.

BACKGROUND: Anti-TNF agents are the only effective biological agents for the prevention of postoperative recurrence (POR) in Crohn's disease (CD). However, they are contraindicated or have been shown to fail in some patients. Although ustekinumab and vedolizumab were licensed for CD some years ago, data in this setting are scarce. METHODS: All CD patients in whom ustekinumab or vedolizumab was prescribed for the prevention of POR within three months of ileocolonic resection with anastomosis were identified from the ENEIDA registry. The development of endoscopic, clinical and surgical POR was registered. RESULTS: Forty patients were treated for the prevention of POR with ustekinumab and 25 were treated with vedolizumab. Eighty per cent had at least one risk factor for POR (prior resections, active smoking, perianal disease or penetrating disease behaviour). All the patients had been exposed to anti-TNF therapy. After a median follow-up of 17 and 26 months, the cumulative probability of clinical POR at 12 months after surgery was 32% and 30% for ustekinumab and vedolizumab, respectively. Endoscopic assessment within the first 18 months after surgery was available for 80% of the patients on ustekinumab and 70% for those on vedolizumab. The rate of endoscopic POR was 42% for ustekinumab and 40% for vedolizumab. One patient treated with ustekinumab and two with vedolizumab underwent a new intestinal resection. CONCLUSIONS: Ustekinumab and vedolizumab seem to be effective in the prevention of POR in patients at high risk. Our results warrant controlled trials comparing these drugs with conventional therapies.

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.

Pre-procedural antibody testing for SARS-CoV-2 in the routine endoscopic practice.

METHODS: a retrospective multicenter cohort study was performed of all endoscopic procedures performed between April 27 and June 15, 2020. A screening questionnaire (SQ) was performed with patients three days prior to the procedure and 14 days after. Furthermore, a serologic SARS-CoV-2 test was performed 48 hours before. RESULTS: two hundred and eleven consecutive patients with endoscopic procedures were included. No patients had a positive SQ, either on entry to the study or 14 days later. Only four patients (1.9 % [95 % CI: 0.07-4.8 %]) were positive for antibodies. CONCLUSION: the pre-endoscopy seroprevalence of SARS-CoV-2 is low in this cohort. Pre-procedural SARS-CoV-2 antibody testing does not add any benefit over clinical SQ to identify active COVID-19 patients.

Predictive factors of clinical response to treatment with anti-TNF agents in ulcerative colitis: what have we learned from our patients?

INTRODUCTION: inhibitors of tumor necrosis factor alpha (anti-TNFs) are effective drugs for the treatment of moderate-to-severe ulcerative colitis (UC). However, many patients do not respond or lose therapeutic response during follow-up. OBJECTIVES: to analyze the determining factors of clinical response to anti-TNFs in UC. METHODS: a multicenter retrospective study was performed in 79 patients with UC who started treatment with anti-TNFs between 2009 and 2015. The primary endpoint was clinical remission (pMayo index ≤ 1) at 12 months. Furthermore, remission and clinical response (final pMayo score ≤ 3) and corticoids discontinuation were assessed at three, six and 12 months. An analysis was performed to identify variables predictive of clinical response. RESULTS: at 12 months, remission and clinical response were seen in 59.2 % and 77.8 % of patients, respectively. Corticoids could be discontinued in 82.4 % of patients. At 12 months, corticoids discontinuation (< 3 months) (OR 0.06; 95 % CI: 0.01-0.24) and clinical response at six months (OR 0.008; 95 % CI: 0.001-0.053) were independent factors predictive of clinical remission. CONCLUSION: in patients with active UC on anti-TNFs, corticoid discontinuation within three months and clinical response at six months after treatment onset are predictive of clinical disease remission.

Usefulness of magnetic resonance enterography in the clinical decision-making process for patients with inflammatory bowel disease.

OBJECTIVE: To evaluate the impact of magnetic resonance enterography (MRE) diagnosis on clinical decision-making regarding treatment choice and maintenance of treatment over time in patients with inflammatory bowel disease (IBD). METHODS: A cohort of patients who underwent MRE for IBD assessment between 2011 and 2014 was analyzed. From clinical records, we retrospectively retrieved their demographic data and clinical data on their IBD at the time of MRE, the results of MRE and the patient's clinical course. Medical management decisions made during the three months following MRE and at the 15-month follow-up were assessed. RESULTS: In total, 474 MREs were reviewed. In the first three-month period, MRE results led to changes in the medical management of 266 patients (56.1%). Of those, maintenance therapy was altered in 140 patients (68.3%) (90.7% step-up and 9.3% top-down strategy), 65 (24.4%) were prescribed a course of steroids and 61 (22.9%) underwent surgery. MRE confirmed a CD diagnosis in 14/41 patients (34.1%) previously diagnosed with indeterminate colitis or ulcerative colitis and in 4/18 patients (22.2%) with suspected IBD. At the 15-month follow-up, treatment remained unchanged in 289 patients (65.8%). CONCLUSIONS: These results suggest that MRE is a diagnostic tool that provides valid information for the clinical-decision making process for patients with CD.

Serial Tuberculin Skin Tests Improve the Detection of Latent Tuberculosis Infection in Patients With Inflammatory Bowel Disease.

AIM: To assess the likelihood of detecting latent tuberculosis infection [LTBI] by the positive conversion of a serial tuberculin skin test [TST] at 1 year in inflammatory bowel disease [IBD] patients with negative baseline two-step TST. METHODS: In this multicentre prospective cohort study, we evaluated rate and predictors of conversion of TST at 1 year in patients with negative baseline TST. We also evaluated management of patients who had a positive TST at baseline or a conversion at 1 year. In all patients we assessed TB cases occurring during follow-up. RESULTS: Of the 192 IBD patients receiving anti-tumour necrosis factor [TNF] and 220 IBD controls not receiving anti-TNF, 35 [8.5%, 95% CI 5.7-11.3] had positive conversion (median TST induration 13 mm, interquartile range [IQR] 9-16). Ten anti-TNF cohort patients [5.2%, 95% CI 2.5-9.5] versus 25 controls [11.4%, 95% CI 7.5-16.3] had TST conversion [p = 0.029]. In multivariate analysis, conversion was associated with smoking habit (odds ratio [OR] 2.19, 95% CI 1.08-3.97; p = 0.028). Anti-TNF-treated patients had a lower conversion rate [OR 0.41, 95% CI 0.20-0.83; p = 0.013]. The likelihood of conversion correlates with fewer immunosuppressive therapies between baseline TST and TST at 1 year [p = 0.042]. One case of active TB [isoniazid-resistant strain] occurred in a patient with positive baseline TST receiving anti-TNF [0.05 events/100 patient-years]. CONCLUSIONS: Serial TST at 1 year can detect LTBI in IBD patients receiving anti-TNF therapy with negative baseline TST. Serial TST seems to be advisable to reduce the risk of TB cases associated with inability to detect LTBI in pre-treatment screening.

Early Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIM: Sensitivity of tuberculin skin test [TST] during screening for latent tuberculosis infection [LTBI] is affected by steroid and/or immunosuppressant therapy. The aim of this study was to compare performance of the two-step TST in inflammatory bowel disease patients immediately before anti-tumour necrosis factor [TNF] therapy as part of routine screening for LTBI vs control patients when the TST was carried out at an early stage. METHODS: In this multicentre prospective controlled study, we evaluated the performance of two-step TST with 5-mm threshold. Factors associated with TST results were determined by logistic regression. RESULTS: We evaluated 243 candidates for anti-TNF therapy and 337 control patients. Overall, 105 patients [18.1%] had an induration ≥ 5 mm in the first TST or in TST retest. LTBI was diagnosed in 25% of patients by TST retest. Twenty-eight [11.5%] anti-TNF group patients vs 77 [22.8%] control patients had a positive TST (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.28-0.70; P < 0.001]. In multivariate analysis, positive TST was associated with higher age [OR 2.63, 95% CI 1.21-5.72; P < 0.001] and 5-aminosalicylate therapy [OR 1.86, 95% CI 1.14-3.05; P = 0.013]. Negative TST was associated with steroid therapy [OR 0.36, 95% CI 0.16-0.83; P = 0.016], immunosuppressant therapy [OR 0.36, 95% CI 0.21-0.62; P < 0.001], or steroids + immunosuppressant therapy [OR 0.20, 95% CI 0.07-0.59; P = 0.004]. CONCLUSIONS: The sensitivity of routine TST performed just before starting anti-TNF therapy is low. TST performed at an early stage enables screening in the absence of immunosuppressive treatment and thus maximises the diagnostic yield of TST for detecting LTBI.

Application of the Barcelona Clinic Liver Cancer therapeutic strategy and impact on survival.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) classification of hepatocellular carcinoma (HCC) has proved useful in the management of HCC patients. However, BCLC-recommended first-line treatment is not always applicable in clinical practice. OBJECTIVE: We performed a multicentre retrospective analysis of reasons for deviation from first-line treatment in 2008-2012. METHODS: One to three-year survival data were analysed using Kaplan-Meier method. RESULTS: A total of 407 consecutive HCC patients (66.6 ± 3 years, 83% male) with cirrhosis were included. Tumours were detected during surveillance in 53% of patients, grouped as Child-Pugh A (67%), B (25%) and C (8%); and BCLC A (including stage 0, 44%), B (26%), C (15%) and D (15%). In 31% of patients, first-line treatment was not feasible (51% in early stages) due to: technical reasons (74%); patient non-conformity (20%); medical decision (3%); and disease progression (3%). One to three-year survival of patients not receiving the recommended first-line treatment was similar to that of patients treated according to BCLC recommendations (log-rank, p = 0.229). CONCLUSION: In real-life practice one-third of HCC patients could not receive first-line BCLC treatment. In our cohort of patients, similar short and medium-term survival was observed. Long-term prospective studies are required to determine the best alternative treatment option when BCLC first-line treatment is not feasible.