Effectiveness and safety of a third-line rescue treatment for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study).

BACKGROUND: The advent of new therapeutic agents and the improvement of supporting care might change the management of acute severe ulcerative colitis (ASUC) and avoid colectomy. AIMS: To evaluate the colectomy-free survival and safety of a third-line treatment in patients with ASUC refractory to intravenous steroids and who failed either infliximab or ciclosporin. METHODS: Multicentre retrospective cohort study of patients with ASUC refractory to intravenous steroids who had failed infliximab or ciclosporin and received a third-line treatment during the same hospitalisation. Patients who stopped second-line treatment due to disease activity or adverse events (AEs) were eligible. We assessed short-term colectomy-free survival by logistic regression analysis. Kaplan-Meier curves and Cox regression models were used for long-term assessment. RESULTS: Among 78 patients, 32 received infliximab and 46 ciclosporin as second-line rescue treatment. Third-line treatment was infliximab in 45 (58%), ciclosporin in 17 (22%), tofacitinib in 13 (17%) and ustekinumab in 3 (3.8%). Colectomy was performed in 29 patients (37%) during follow-up (median 21 weeks). Of the 78 patients, 32 and 18 were in clinical remission at, respectively, 12 and 52 weeks. At the last visit, 25 patients were still on third-line rescue treatment, while 12 had stopped it due to clinical remission. AEs were reported in 26 (33%) patients. Two patients died (2.6%), including one following colectomy. CONCLUSION: Third-line rescue treatment avoided colectomy in over half of the patients with ASUC and may be considered a therapeutic strategy.

Evaluation of genetic variants associated with the risk of thiopurine-related pancreatitis: a case control study from ENEIDA registry.

BACKGROUND: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. AIM: Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled, 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis, and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

Prophylactic versus endoscopy-driven treatment of Crohn's postoperative recurrence: A retrospective, multicentric European study (PORCSE study).

BACKGROUND AND AIMS: No consensus exists on optimal strategy to prevent postoperative recurrence (POR) after ileocecal resection (ICR) for Crohn's disease (CD).We compared early medical prophylaxis versus expectant management with treatment driven by findings at elective endoscopy 6-12 months after ICR. METHODS: A retrospective, multicentric, observational study was performed. CD-patients undergoing first ICR were assigned to cohort1 if a biologic or immunomodulator was (re)started prophylactically after ICR, or to cohort2 if no postoperative prophylaxis was given and treatment was started as reaction to elective endoscopic findings. Primary endpoint was rate of endoscopic POR (Rutgeerts>i1). Secondary endpoints were severe endoscopic POR (Rutgeerts i3/i4), clinical POR, surgical POR and treatment burden during follow-up. RESULTS: Of 346 included patients, 47.4% received prophylactic postoperative treatment (proactive/cohort1) and 52.6% did not (reactive/cohort2).Endoscopic POR (Rutgeerts>i1) rate was significantly higher in cohort2 (41.5% vs 53.8%, OR1.81, P=0.039) at endoscopy 6-12 months after surgery. No significant difference in severe endoscopic POR was found (OR1.29, P=0.517). Cohort2 had significantly higher clinical POR rates (17.7% vs 35.7%, OR3.05, P=0.002) and numerically higher surgical recurrence rates (6.7% vs 13.2%, OR2.59, P=0.051). Cox proportional hazards regression analysis showed no significant difference in time to surgical POR of proactive versus expectant/reactive approach (HR2.50, P=0.057). Quasi-Poisson regression revealed a significantly lower treatment burden for immunomodulator use in cohort2 (mean ratio 0.53, P=0.002), but no difference in burden of biologics or combination treatment. CONCLUSIONS: The PORCSE study showed lower rates of endoscopic POR with early postoperative medical treatment compared to expectant management after first ileocecal resection for Crohn's disease.

Headache in patients with inflammatory bowel disease: Migraine prevalence according to the Migraine Screening-Questionnaire (MS-Q) and headache characteristics / Cefalea en pacientes con enfermedad inflamatoria intestinal: prevalencia de migraña de acuerdo al Migraine Screening-Questionnaire (MS-Q) y características de la cefalea

Background The gut-brain axis describes a complex bidirectional association between neurological and gastrointestinal (GI) disorders. In patients with migraine, GI comorbidities are common. We aimed to evaluate the presence of migraine among patients with inflammatory bowel disease (IBD) according to Migraine Screen-Questionnaire (MS-Q) and describe the headache characteristics compared to a control group. Additionally, we explored the relationship between migraine and IBD severities. Methods We performed a cross-sectional study through an online survey including patients from the IBD Unit at our tertiary hospital. Clinical and demographic variables were collected. MS-Q was used for migraine evaluation. Headache disability scale HIT-6, anxiety-depression scale HADS, sleep scale ISI, and activity scale Harvey–Bradshaw and Partial Mayo scores were also included. Results We evaluated 66 IBD patients and 47 controls. Among IBD patients, 28/66 (42%) were women, mean age 42 years and 23/66 (34.84%) had ulcerative colitis. MS-Q was positive in 13/49 (26.5%) of IBD patients and 4/31 (12.91%) controls (p=0.172). Among IBD patients, headache was unilateral in 5/13 (38%) and throbbing in 10/13 (77%). Migraine was associated with female sex (p=0.006), lower height (p=0.003) and weight (p=0.002), anti-TNF treatment (p=0.035). We did not find any association between HIT-6 and IBD activity scales scores. Conclusions Migraine presence according to MS-Q could be higher in patients with IBD than controls. We recommend migraine screening in these patients, especially in female patients with lower height and weight and anti-TNF treatment (AU)

Introducción El eje intestino-cerebro describe una asociación bidireccional compleja entre las enfermedades neurológicas y gastrointestinales (GI). Las comorbilidades GI son frecuentes en la migraña. Nuestro objetivo fue evaluar la presencia de migraña en pacientes con enfermedad inflamatoria intestinal (EII) y describir las características de la cefalea. Además, analizamos la relación entre la gravedad de la migraña y la EII. Métodos Estudio transversal a través de encuesta electrónica en pacientes con EII de un hospital terciario. Se recogieron variables clínicas y demográficas. Se usó MS-Q para presencia de migraña. Se incluyeron escala de discapacidad de cefalea HIT-6, ansiedad-depresión HADS, sueño ISI y actividad de EII Harvey-Bradshaw y Partial Mayo. Resultados Se incluyeron 66EII y 47controles. Entre los EII, 28/66 (42%) eran mujeres, con una edad media de 42años, y 23/66 (34,84%) tenían colitis ulcerosa. El MS-Q fue positivo en 13/49 (26,5%) de EII y en 4/31 (12,91%) controles (p=0,172). Entre los pacientes con EII, la cefalea fue unilateral en 5/13 (38%) y pulsátil en 10/13 (77%). El sexo femenino (p=0.006), la altura (p=0,003) y el peso más bajos (p=0,002) y el tratamiento con anti-TNF (p=0,035) se relacionaron con la probabilidad de migraña. No encontramos asociación entre el HIT-6 y las escalas de actividad de EII. Conclusiones La presencia de migraña de acuerdo al MS-Q podría ser más alta en los pacientes con EII que en controles. Recomendamos realizar un cribado de migraña en estos pacientes, especialmente en mujeres de menor peso y altura y tratamiento anti-TNF (AU)

Headache in patients with inflammatory bowel disease: Migraine prevalence according to the Migraine Screening-Questionnaire (MS-Q) and headache characteristics.

BACKGROUND: The gut-brain axis describes a complex bidirectional association between neurological and gastrointestinal (GI) disorders. In patients with migraine, GI comorbidities are common. We aimed to evaluate the presence of migraine among patients with inflammatory bowel disease (IBD) according to Migraine Screen-Questionnaire (MS-Q) and describe the headache characteristics compared to a control group. Additionally, we explored the relationship between migraine and IBD severities. METHODS: We performed a cross-sectional study through an online survey including patients from the IBD Unit at our tertiary hospital. Clinical and demographic variables were collected. MS-Q was used for migraine evaluation. Headache disability scale HIT-6, anxiety-depression scale HADS, sleep scale ISI, and activity scale Harvey-Bradshaw and Partial Mayo scores were also included. RESULTS: We evaluated 66 IBD patients and 47 controls. Among IBD patients, 28/66 (42%) were women, mean age 42 years and 23/66 (34.84%) had ulcerative colitis. MS-Q was positive in 13/49 (26.5%) of IBD patients and 4/31 (12.91%) controls (p=0.172). Among IBD patients, headache was unilateral in 5/13 (38%) and throbbing in 10/13 (77%). Migraine was associated with female sex (p=0.006), lower height (p=0.003) and weight (p=0.002), anti-TNF treatment (p=0.035). We did not find any association between HIT-6 and IBD activity scales scores. CONCLUSIONS: Migraine presence according to MS-Q could be higher in patients with IBD than controls. We recommend migraine screening in these patients, especially in female patients with lower height and weight and anti-TNF treatment.

Comparative Study of the Effectiveness of Vedolizumab Versus Ustekinumab After Anti-TNF Failure in Crohn's Disease (Versus-CD): Data from the ENEIDA Registry.

BACKGROUND: Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited. AIMS: To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. METHODS: CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. RESULTS: A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02-3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00-1.62], moderate-severe activity in HBI [HR 1.79; 95% CI: 1.20-2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02-1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them. CONCLUSION: In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.

Long Non-Coding RNA Signatures in the Ileum and Colon of Crohn's Disease Patients and Effect of Anti-TNF-α Treatment on Their Modulation.

Biological therapies only benefit one-third of patients with Crohn's disease (CD). For this reason, a deeper understanding of the mechanisms by which biologics elicit their effect on intestinal mucosa is needed. Increasing evidence points toward the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of CD, although their role remains poorly studied. We aimed to characterize lncRNA profiles in the ileum and colon from CD patients and evaluate the effect of anti-TNF-α treatment on their transcription. Terminal ileum and left colon samples from 30 patients (active CD = 10, quiescent CD = 10, and healthy controls (HCs) = 10) were collected for RNA-seq. The patients were classified according to endoscopic activity. Furthermore, biopsies were cultured with infliximab, and their transcriptome was determined by Illumina gene expression array. A total of 678 differentially expressed lncRNAs between the terminal ileum and left colon were identified in HCs, 438 in patients with quiescent CD, and 468 in patients with active CD. Additionally, we identified three new lncRNAs in the ileum associated with CD activity. No differences were observed when comparing the effect of infliximab according to intestinal location, presence of disease (CD vs. HC), and activity (active vs. quiescent). The expression profiles of lncRNAs are associated with the location of intestinal tissue, being very different in the ileum and colon. The presence of CD and disease activity are associated with the differential expression of lncRNAs. No modulatory effect of infliximab has been observed in the lncRNA transcriptome.

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.

Real-world outcomes of switching from adalimumab originator to adalimumab biosimilar in patients with inflammatory bowel disease: The ADA-SWITCH study.

BACKGROUND AND AIMS: Data on the outcomes after switching from adalimumab (ADA) originator to ADA biosimilar are limited. The aim was to compare the treatment persistence, clinical efficacy, and safety outcomes in inflammatory bowel disease patients who maintained ADA originator vs. those who switched to ADA biosimilar. METHODS: Patients receiving ADA originator who were in clinical remission at standard dose of ADA originator were included. Patients who maintained ADA originator formed the non-switch cohort (NSC), and those who switched to different ADA biosimilars constituted the switch cohort (SC). Clinical remission was defined as a Harvey-Bradshaw index ≤4 in Crohn's disease and a partial Mayo score ≤2 in ulcerative colitis. To control possible confounding effects on treatment discontinuation, an inverse probability treatment weighted proportional hazard Cox regression was performed. RESULTS: Five hundred and twenty-four patients were included: 211 in the SC and 313 in the NSC. The median follow-up was 13 months in the SC and 24 months in the NSC (p < 0.001). The incidence rate of ADA discontinuation was 8% and 7% per patient-year in the SC and in the NSC, respectively (p > 0.05). In the multivariate analysis, switching from ADA originator to ADA biosimilar was not associated with therapy discontinuation. The incidence rate of relapse was 8% per patient-year in the SC and 6% per patient-year in the NSC (p > 0.05). Six percent of the patients had adverse events in the SC vs. 5% in the NSC (p > 0.05). CONCLUSION: Switching to ADA biosimilar did not impair patients' outcomes in comparison with maintaining on the originator.

Clinical Presentation, Management, and Evolution of Lymphomas in Patients with Inflammatory Bowel Disease: An ENEIDA Registry Study.

An increased risk of lymphoma has been described in patients with inflammatory bowel disease (IBD). The aims of our study were to determine the clinical presentation, the previous exposure to immunosuppressive and biologic therapies, and the evolution of lymphomas in patients with IBD. IBD patients with diagnosis of lymphoma from October 2006 to June 2021 were identified from the prospectively maintained ENEIDA registry of GETECCU. We identified 52 patients (2.4 cases of lymphoma/1000 patients with IBD; 95% CI 1.8-3.1). Thirty-five were men (67%), 52% had ulcerative colitis, 60% received thiopurines, and 38% an anti-TNF drug before lymphoma diagnosis. Age at lymphoma was lower in those patients treated with thiopurines (53 ± 17 years old) and anti-TNF drugs (47 ± 17) than in those patients not treated with these drugs (63 ± 12; p < 0.05). Five cases had relapse of lymphoma (1.7 cases/100 patient-years). Nine patients (17%) died after 19 months (IQR 0-48 months). Relapse and mortality were not related with the type of IBD or lymphoma, nor with thiopurines or biologic therapies. In conclusion, most IBD patients had been treated with thiopurines and/or anti-TNF agents before lymphoma diagnosis, and these patients were younger at diagnosis of lymphoma than those not treated with these drugs. Relapse and mortality of lymphoma were not related with these therapies.

ECCO Topical Review on Biological Treatment Cycles in Crohn's Disease.

There are now a growing number of licensed biological therapies for patients with Crohn's disease. However, there can be significant costs associated with long-term maintenance treatment, as well as some concerns about potential side-effects. As a result, there has been increasing interest in elective biological treatment discontinuation in selected patients, after a sustained period of remission. Following discontinuation, in cases of relapse, evidence to date has suggested that remission may often be regained by re-treatment with the same biological agent. Therefore, a concept has emerged in which cycles of biological therapy might be used. If this treatment strategy were to be applied in a subgroup of patients at low risk of relapse, cycling might allow a substantial number of patients to have a lower, overall therapeutic burden-ensuring decreased exposure to biological therapy but still enabling appropriate disease control. Currently, there remains uncertainty about the benefit-risk balance for using cycles of biological treatment for patients with Crohn's disease. Accordingly, an expert panel was convened by the European Crohn's and Colitis Organisation [ECCO] to review the published literature and agree a series of consensus practice points. The panel aimed to provide evidence-based guidance on multiple aspects of biological treatment discontinuation and cycling, including the risk of relapse after elective treatment discontinuation, predictors of probable relapse or remission, safety, patient preferences, and pharmacoeconomic aspects. Crucially, discussions about biological treatment discontinuation and cycling should be individualized, to enable shared decision-making by patients with their clinicians.

Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Correction: Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885.

The authors wish to make the following corrections to this paper [...].

Differential Effects of Anti-TNFα and Anti-α4ß7 Drugs on Circulating Dendritic Cells Migratory Capacity in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is an idiopathic and chronic disorder that includes ulcerative colitis (UC) and Crohn's disease (CD). Both diseases show an uncontrolled intestinal immune response that generates tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells that play a key role in tolerance maintenance in the gastrointestinal mucosa. Although it has been reported that DC recruitment by the intestinal mucosa is more prominent in IBD patients, the specific mechanisms governing this migration are currently unknown. In this study, the expression of several homing markers and the migratory profile of circulating DC subsets towards intestinal chemo-attractants were evaluated and the effect of biological drugs with different mechanisms of action, such as anti-TNFα or anti-integrin α4ß7 (vedolizumab), on this mechanism in healthy controls (HCs) and IBD patients was also assessed. Our results revealed that type 2 conventional DCs (cDC2) express differential homing marker profiles in UC and CD patients compared to HCs. Indeed, integrin ß7 was differentially modulated by vedolizumab in CD and UC. Additionally, although CCL2 displayed a chemo-attractant effect over cDC2, while biological therapies did not modulate the expression of the homing markers, we paradoxically found that anti-TNF-treated cDC2 increased their migratory capacity towards CCL2 in HCs and IBD. Our results therefore suggest a key role for cDC2 migration towards the intestinal mucosa in IBD, something that could be explored in order to develop novel diagnostic biomarkers or to unravel new immunomodulatory targets in IBD.

Características epidemiológicas, clínicas y respuesta al tratamiento en 113 pacientes con colitis microscópica / Epidemiological and clinical characteristics, and response to treatment in 113 patients with microscopic colitis

Objetivo: Estudiar las características epidemiológicas, clínicas y la respuesta al tratamiento en pacientes con colitis microscópica. Pacientes y método: Se recopilaron retrospectivamente los datos epidemiológicos, clínicos, analíticos y endoscópicos de 113 pacientes con colitis microscópica. La respuesta al tratamiento se analizó en 104 de ellos. La eficacia y la recidiva tras la administración de budesonida se evaluaron mediante curvas de supervivencia (Kaplan-Meier). Resultados: El 78% de los pacientes fueron mujeres, con una edad media de 65 ± 16 años. En los fumadores, la edad media fue 10 años menor. Un 48% tenía alguna enfermedad inmunomediada concomitante. El 60% sufrió un único brote de la enfermedad. La presentación clínica fue similar en ambos subtipos, aunque los pacientes con colitis colágena tuvieron con mayor frecuencia un curso crónico (48 vs. 29%, p = 0,047). La tasa de remisión con budesonida fue del 93% (IC 95%: 82-98). La incidencia acumulada de recidiva, tras una mediana de seguimiento de 21 meses, fue del 39% (IC 95%: 26-54%): 19% al año, 32% a los dos años y 46% a los tres años de seguimiento. No hubo diferencias en la respuesta clínica a la budesonida en función del tabaquismo o del subtipo de colitis microscópica. Conclusiones: La colitis microscópica es más frecuente en mujeres de edad avanzada. El tabaco se asoció a una aparición más precoz de la enfermedad, aunque no influyó en la evolución clínica o en la respuesta al tratamiento. La mayoría (> 90%) de los pacientes tratados con budesonida alcanzaron la remisión, aunque casi la mitad recidivaron posteriormente.(AU)

Objective: To study the epidemiological and clinical characteristics, and response to treatment in patients with microscopic colitis. Patients and method: Epidemiological, clinical, blood test and endoscopic data were retrospectively collected from 113 patients with microscopic colitis. Response to treatment was analyzed in 104 of them. Efficacy and relapse after treatment with budesonide were assessed using survival curves (Kaplan-Meier). Results: 78% of the patients were women, with a mean age of 65 ± 16 years. In smokers, the mean age was 10 years younger. 48% of them had some concomitant autoimmune disease; 60% suffered a single outbreak of the disease. The clinical presentation was similar in both subtypes, although patients with collagenous colitis had a chronic course more frequently (48% vs. 29%, p = 0.047). The remission rate with budesonide was 93% (95% CI 82-98). The cumulative incidence of relapse, after a median follow-up of 21 months, was 39% (95% CI 26-54%): 19% at one year, 32% at two years, and 46% at three years of follow-up. There were no differences in clinical response to budesonide based on smoking habit or microscopic colitis subtype. Conclusions: Microscopic colitis is more frequent in elderly women. Smoking was associated with earlier onset of the disease, although it did not influence the clinical course or response to treatment. The majority (> 90%) of patients treated with budesonide achieved remission, although nearly half subsequently relapsed.(AU)

Clinical features, therapeutic requirements and evolution of patients with Crohn's disease and upper gastrointestinal involvement (CROHNEX study).

BACKGROUND: Crohn's disease (CD) with upper gastrointestinal involvement (UGI) may have a more aggressive and refractory course. However, evidence on this phenotype of patients is scarce. AIMS: To identify the clinical characteristics, therapeutic requirements and complications associated with UGI in CD METHODS: Nationwide study of cases (UGI, UGI plus ileal/ileocolonic involvement) paired with controls (ileal/ileocolonic involvement) from the ENEIDA registry. Cases were matched to 2 controls by year of diagnosis ± 2.5 years. Patients with exclusive/predominant colonic location or complex perianal fistula were excluded. RESULTS: Of 24 738 patients with CD in the ENEIDA registry, we identified 4058 with UGI (16% of the total CD cohort). Finally, 854 cases and 1708 controls were included. Cases were independently associated to extensive involvement (OR 2.7 [2.2-3.3], P < 0.0001), strictures [OR 1.8 (1.5-2.2), P < 0.0001], chronic iron deficiency anaemia [OR 2.2 (1.3-3.2), P < 0.001] and use of second-line biologics [OR 1.7 (1.1-2.6), P = 0.021]. The median stricture-free time was 14 years (95% CI, 12-16) for cases vs 21 years (95% CI, 19-23) for controls (P < 0.0001). Cases with isolated UGI compared to UGI plus ileal/ileocolonic more frequently had localised disease [OR 0.5(0.3-0.8), P = 0.003] and underwent more endoscopic stricture dilations [OR 2.7(1.3-5.4), P = 0.006]. CONCLUSIONS: The largest cohort of patients with CD and UGI provides information on the natural history of this particular phenotype. Increased awareness of the clinical picture and therapeutic requirements of these patients could lead to earlier diagnosis and treatment of upper gastrointestinal lesions, preventing the structural damage frequently seen in these patients at diagnosis and 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.

Clinical outcome after anti-tumour necrosis factor therapy discontinuation in 1000 patients with inflammatory bowel disease: the EVODIS long-term study.

BACKGROUND: The long-term outcome of patients after antitumour necrosis factor alpha (anti-TNF) discontinuation is not well known. AIMS: To assess the risk of relapse in the long-term after anti-TNF discontinuation. METHODS: This was an extension of the evolution after anti-TNF discontinuation in patients with inflammatory bowel disease (EVODIS) study (Crohn's disease or ulcerative colitis patients treated with anti-TNFs in whom these drugs were withdrawn after achieving clinical remission) based in the same cohort of patients whose outcome was updated. Clinical remission was defined as a Harvey-Bradshaw index ≤4 points in Crohn's disease, a partial Mayo score ≤2 in ulcerative colitis and the absence of fistula drainage despite gentle finger compression in perianal disease. RESULTS: This was an observational, retrospective, multicenter study. A total of 1055 patients were included. The median follow-up time was 34 months. The incidence rate of relapse was 12% per patient-year (95% confidence interval [CI] = 11-14). The cumulative incidence of relapse was 50% (95% CI = 47-53): 19% at one year, 31% at 2 years, 38% at 3 years, 44% at 4 years and 48% at 5 years of follow-up. Of the 60% patients retreated with the same anti-TNF after relapse, 73% regained remission. Of the 75 patients who did not respond, 48% achieved remission with other therapies. Of the 190 patients who started other therapies after relapse, 62% achieved remission with the new treatment. CONCLUSIONS: A significant proportion of patients who discontinued the anti-TNF remained in remission. In case of relapse, retreatment with the same anti-TNF was usually effective. Approximately half of the patients who did not respond after retreatment achieved remission with other therapies.

Effectiveness and Safety of Ustekinumab in Ulcerative Colitis: Real-world Evidence from the ENEIDA Registry.

BACKGROUND AND AIMS: The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life. METHODS: Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16. RESULTS: A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. CONCLUSIONS: Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.