BACKGROUND:The expanding use of targeted therapies in inflammatory bowel disease has made treatment sequencing increasingly relevant, yet evidence on anti-TNF effectiveness after prior biologics with different mechanisms of action (MOA) remains limited. Our objective is to evaluate the durability of anti-TNF treatment in this scenario. METHODS:Multicentre study based on data from the ENEIDA registry. Patients who received second-line anti-TNF therapy after a first biologic with a different MOA for active luminal disease were identified. Using propensity score matching, each case was matched with three controls from two cohorts: patients treated with second-line anti-TNF after another anti-TNF and patients receiving first-line anti-TNF therapy. Treatment durability and short- and long-term clinical effectiveness were assessed. RESULTS:Sixty-six Crohn's disease patients and 117 UC patients receiving anti-TNF after other MOA were included. In CD, second-line anti-TNF therapy after a different MOA (62% ustekinumab) was associated with a higher risk of treatment discontinuation compared with first-line anti-TNF therapy (HR 1.55; 95% CI, 1.05-2.30), without significant differences in short- or long-term clinical effectiveness. In UC, anti-TNF therapy after a different MOA (90% vedolizumab) was associated with lower treatment durability compared with first-line anti-TNF therapy (HR 1.69; 95% CI, 1.31-2.19) and with anti-TNF after another anti-TNF agent (HR 1.91; 95% CI, 1.48-2.48), its remission rates significantly lower at both short- and long-term follow-up (p < 0.001). CONCLUSIONS:Anti-TNF therapy used after a different MOA is associated with reduced effectiveness and durability compared with its use as first-line therapy or after another anti-TNF agent, especially in UC.

BACKGROUND:Comprehensive inflammatory bowel disease (IBD) units have been implemented to improve the quality of care delivered to patients with Crohn's disease and ulcerative colitis. Although accreditation programmes have improved structural and process quality indicators, little is known about their association with patients' healthcare experience. AIM:To compare patient-reported experience between patients receiving care in accredited and non-accredited IBD units. Secondary objectives were to compare perceived disease activity and selected organisational quality indicators. METHODS:Cross-sectional online survey conducted among members of the Associació de Malalts de Crohn i Colitis Ulcerosa de Catalunya. The questionnaire included nine prespecified individual PREM indicators previously developed and used by our group, a global five-point satisfaction score, the Manitoba Index and organisational quality indicators. Hospitals were classified as having or not having an accredited IBD unit according to the official information of the Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa. Comparisons were performed using univariate analyses. RESULTS:A total of 127 valid questionnaires were analysed (95 accredited units; 32 non-accredited units). All nine PREM showed significantly better scores in accredited units. Overall satisfaction was also significantly higher among patients attending accredited units, which also scored better for organisational quality indicators. No statistically significant difference was observed in disease activity measured by the Manitoba Index. CONCLUSIONS:Accredited IBD units are associated with substantially better patient-reported experience without statistically significant differences in patient-reported disease activity. These findings provide patient-centred evidence supporting this model of care.

BACKGROUND:Real-world data on dose escalation/de-escalation in inflammatory bowel disease (IBD) are scarce. AIMS:To assess the frequency, effectiveness and durability of escalation/de-escalation of infliximab, adalimumab, golimumab, vedolizumab and ustekinumab in IBD, and to identify factors influencing relapse and drug discontinuation and re-escalation efficacy. METHODS:We included patients from the ENEIDA registry of GETECCU who were exposed to biologics and analysed escalations/de-escalations. We assessed the impact of variables on durability, drug discontinuation and relapse after escalation/de-escalation. RESULTS:Of 19,720 patients on biologics, 5096 (26%) underwent dose escalation. Frequency of escalation per patient-year was 5% (infliximab), 7% (adalimumab), 7% (golimumab), 10% (vedolizumab) and 12% (ustekinumab). Clinical remission was recaptured in 32%-49% of patients. Durability of escalation (24 months) ranged from 66% to 88%. Drug discontinuation was associated with previous biologic exposure and disease duration (infliximab), monotherapy (adalimumab) and ulcerative colitis (ustekinumab). There were 669 de-escalations. The frequency per patient-year was 6%, 9%, 5%, 6% and 3% for infliximab, adalimumab, golimumab, vedolizumab and ustekinumab. Maintenance of remission after de-escalation was observed in 75%-100%. Durability of de-escalation (12 months) was 82%-90%. Factors associated with relapse were biologic exposure (infliximab) and age at de-escalation (adalimumab). Re-escalation benefited most patients. CONCLUSIONS:In the long term, some patients with IBD need biologic escalation, which frequently recaptures durable clinical remission. De-escalation is feasible in some patients. Re-escalation is generally effective after relapse.

ABSTRACTBackgroundLeishmaniasis (LI) is a vector‐borne illness caused by a protozoan of the genus Leishmania. Data on the features of LI in patients with inflammatory bowel disease (IBD) are scarce.AimTo describe the characteristics of patients with IBD who present with leishmaniasis, infection outcomes and the risk factors associated with developing visceral leishmaniasis (VL).MethodsAn observational retrospective study performed in 26 hospitals in Spain, including all adult patients with IBD who developed Leishmaniasis from 2012 to 2022.ResultsA total of 73 patients were included [mean age 48 years; 65% male; 68% Crohn's disease]. Sixty patients (82.2%) presented localized cutaneous Leishmaniasis (CL), 2 (2.7%) diffuse CL, 3 (4.1%) mucocutaneous Leishmaniasis (MCL) and 8 (11%) VL. All patients were under biologicals (69 [94.5%]) or immunosuppressants (IMM) (4 [5.5%]) at Leishmaniasis diagnosis. AntiTNF was used in 97%, while 2 patients (3%) were receiving ustekinumab. Leishmaniasis resolution was achieved by 48% and 96% of the patients after 1 and 12 months, respectively. Biological withdrawal after Leishmaniasis diagnosis was not statistically related to increased rates of infection resolution among patients with localized CL. Age was the only risk factor associated with VL (OR 1.2, 95%CI 1.04–1.39; p = 0.012).ConclusionsLeishmaniasis in patients with IBD doesn't seem to follow a complicated clinical course, even in those with localized CL who do not discontinue biological therapy after infection diagnosis. Age might be a risk factor for developing VL. This infection should be considered for immunosuppressed patients with IBD and suggestive symptoms dwelling or travelling to endemic areas.

Abstract Background Factors influencing the exposure to targeted therapies (biologics/JAKi), intestinal resections and hospitalisations in newly diagnosed IBD patients have been scarcely studied. Aim: To identify predictive factors of exposure to biologics/JAKi, surgeries, and hospitalisations within the first five years in IBD patients. 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 the 17 Spanish regions were included. Patients who consented were followed-up for 5 years after diagnosis. Multivariate analyses were performed to identify the predictive factors for biologics/JAKi use, surgeries, and hospitalisations. To this end, only abdominal surgeries were analysed, and early treatment with immunomodulators or biologics/JAKi drugs were considered if these had been prescribed within the first six months of diagnosis. Results A total of 1,526 patients diagnosed with CD and 1,633 with UC were included (figure 1). The cumulative incidence of exposure to biologics/JAKi drugs, surgeries, and hospitalisations were analysed, and predictive factors were identified. Regarding the predictors of exposure to biologics/JAKi treatments, we observed that younger age, more aggressive phenotype of CD and greater extent of UC were associated with a higher risk of exposure (table 1). Furthermore, smoking was associated with a higher likelihood of exposure to biologics/JAKi drugs in patients with CD (HR=1.33, 95%CI=1.11-1.60) while in UC patients it was associated with a lower risk (HR=0.56, 95%CI=0.35-0.89). Concerning surgeries (table 1), early treatment with immunomodulators was associated with a lower risk in patients with CD (HR=0.33, 95%CI=0.22-0.49), whereas early use of biologics/JAKi drugs was associated with a higher likelihood of surgery in patients with UC (HR=11.86, 95%CI=4.62-30.42). Finally, the exposure to biologics/JAKi drugs was associated with a lower risk of hospital admissions both in patients with CD (HR=0.37, 95%CI=0.24-0.56) and UC (HR=0.45, 95%CI=0.22-0.91) (table 1). Conclusion The exposure to biologics/JAKi drugs is mediated by the more aggressive phenotype of CD, greater extent of UC, and younger patient age. The use of biologics/JAKi drugs, as currently practiced, is associated with a lower risk of hospitalisations but does not reduce the need for surgery, even when administered early. There is an unmet need for more accurate identification of patients who require these treatments to modify the natural course of the disease.

Introduction:Dysbiosis is a key mechanism in inflammatory bowel disease (IBD) pathophysiology. Previous microbiota studies in IBD generally have involved patients treated with immunosuppressive agents, which can affect the results. We aimed to elucidate the fecal microbiota composition in newly diagnosed treatment-naïve IBD patients. Methods:Microbiota from stool samples were investigated using shotgun metagenomics sequencing and subsequent bioinformatics analysis. Results:A total of 103 patients with Crohn's disease (CD), 144 with ulcerative colitis (UC), and 49 healthy controls (HC) were included. CD patients had significantly lower species-level diversity than those with UC and HC. CD subgroups with Ileocolonic location and stricturing behavior showed reduced diversity compared to HC. A negative correlation was observed between endoscopic severity and microbial diversity in CD patients. UC patients had similar microbial diversity to HC, which was unaffected by disease activity. Taxonomic abundance analysis revealed a tendency towards a higher relative abundance of Escherichia coli and a lower relative abundance of Faecalibacterium prausnitzii in IBD patients compared to HC. However, the most significant differences in these patients compared to HC were observed in less abundant species, such as Toxoplasma gondii, Gemella morbillorum, and several species of the Adlercreutzia genera. Functional analysis in these patients highlighted changes in carbohydrate and nucleotide pathways. Discussion:Our data suggest that newly diagnosed CD patients show significant microbiota composition disparities compared to UC patients and HC. Microbiota differences in these patients are linked to dysbiosis, characterized by a reduction in beneficial genera such as Gemella and Adlercreutzia, and a rise in pathogenic species.

Background and Objective While significant advances have been made in identifying biomarkers for predicting inflammatory bowel disease (IBD) onset, little is known about the willingness of at-risk individuals to undergo predictive testing and preventive interventions. This study aimed to assess acceptance of predictive tests and preventive interventions among individuals at risk of inflammatory bowel disease and identify factors influencing their decisions.Methods An anonymized electronic survey was distributed to parents of children at risk of inflammatory bowel disease and first-degree relatives (FDRs) of IBD patients via clinicians and patient associations. The survey assessed acceptance of predictive tests, preventive interventions, and influencing variables.Results A total of 1327 participants (74% women, mean age 42 +/- 18 years) from 66 countries responded to the survey. Of these, 88% were parents of children at risk, and 12% were FDRs. Eighty-five percent were willing to embark in predictive testing, preferring blood analysis (91%), stool tests (89%), saliva tests (78%) or intestinal ultrasound (67%). Lower perceived IBD impact and higher disease knowledge reduced the odds of test acceptance. Preventive interventions were accepted by 98%, with dietary changes (85%), physical exercise (81%), and probiotics (71%) being the preferred. Acceptance of oral (38%) or intravenous/subcutaneous immunosuppressive treatments (32%) depended on their efficacy, difficulty, and risks.Conclusion Most respondents preferred minimally invasive predictive tests and non-pharmacological preventive measures, although more than one-third would be willing to undergo immunosuppressive medications to prevent disease onset. Disease knowledge and quality-of-life perceptions influenced preferences. This data provides important information for the development of IBD prediction and prevention strategies.

BACKGROUND:Limited data are available on the management and outcomes of postoperative Crohn's disease (CD) in older patients. We aimed to describe the management of CD in the postoperative setting and assess surgical postoperative recurrence (POR) in this population. METHODS:This was a case-control study including all adult patients with CD from the ENEIDA registry who had undergone a first intestinal resection with ileo-colonic anastomosis. Patients were grouped according to their age at the time of the first surgery in older (over 60 years) subjects and controls (between 18 and 60 years of age). RESULTS:A total of 3982 (535 older subjects and 3454 controls) underwent a first intestinal resection for CD with an ileo-colonic anastomosis. Time from CD diagnosis to surgery was significantly longer in older patients (114 ± 128 vs. 93 ± 97 months; p < 0.001). Older patients also had a lower proportion of penetrating CD (25% vs. 39%; p < 0.0001) and perianal disease (14% vs. 25%; p < 0.0001). A significantly lower proportion of older patients started preventive therapies for POR (32% vs. 51%; p < 0.0001). The cumulative risk of surgical POR was 3.2%, 5.3% and 10.1% in the older group and 3.6%, 6.6% and 14.2% in the control group at three, five and 10 years, respectively (p = 0.093). In the multivariate logistic regression analysis, only prevention with thiopurines was associated with a lower risk of surgical POR. CONCLUSIONS:Although postoperative preventive therapy with immunomodulators or biologicals is prescribed less often in older patients after a first intestinal resection, they develop surgical POR as often as younger adult patients.

OBJECTIVE:Ulcerative proctitis (UP) usually presents a milder course, but some patients develop significant symptom burden, severe forms, or refractory UP (RUP). Our objective was to characterise RUP and generate recommendations for daily practice. METHODS:A systematic review (SR) was conducted to analyze epidemiological, clinical, and pharmacological treatment aspects of RUP. The results were discussed in a nominal focus group meeting composed of seven gastroenterologists specialized in the management of inflammatory bowel disease, a nurse, and a patient. Several statements on the management of PU were proposed and voted to achieve agreement. RESULTS:The SR included 43 articles of low to moderate quality. Nearly 30% of patients presented RUP, and the impact of the disease on their quality of life was highly significant. Different gaps of knowledge related to the clinical characteristics and course of the disease, efficacy, safety, and selection of pharmacological treatments were identified. The experts proposed 13 practical statements that reached the established level of agreement. These address the diagnosis of UP and RUP, their therapeutic goals and treatment selection, monitoring, treatment response, and the role of the nurse. CONCLUSIONS:RUP is common and can have a significant impact on patients. More research is needed to characterize RUP and the long-term efficacy of available treatments. The proposed statements aim to address the knowledge gaps related to RUP.

Atención primaria es el primer punto de contacto de la mayoría de los pacientes tras el inicio de los síntomas de una enfermedad inflamatoria intestinal (EII). Establecer un proceso diagnóstico inicial ante síntomas compatibles y unos criterios y vías de derivación pactadas, en función del grado de sospecha y de la situación del paciente, puede disminuir los retrasos diagnósticos. Una vez derivado el paciente al especialista de Digestivo y establecido el diagnóstico de EII, se estructura un plan de tratamiento y seguimiento. El manejo del paciente debe ser compartido con la participación del médico de familia en el diagnóstico y el tratamiento de las patologías concomitantes o intercurrentes, el reconocimiento de los brotes o de las complicaciones (de la EII o de los tratamientos), las tareas de educación del paciente o el control de la adherencia.Con el objetivo de realizar una guía integral sobre el manejo de la EII dirigida a médicos de atención primaria se ha elaborado este documento de posicionamiento colaborativo entre la Sociedad Española de Médicos de Atención Primaria (SEMERGEN) y el Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU).

Objetivo: La proctitis ulcerosa (PU) suele tener un curso más leve, pero hay pacientes con una carga sintomática importante, extensión a formas más graves y algunos desarrollan formas refractarias (PUR). Nuestro objetivo fue el de revisar la evidencia sobre la PUR y elaborar una serie de recomendaciones para la práctica diaria.Métodos: Se realizó una revisión sistemática (RS) para analizar aspectos epidemiológicos, clínicos, y relacionados con los tratamientos farmacológicos de la PUR. Sus resultados se discutieron en una reunión de grupo nominal formada por siete gastroenterólogos especialistas en el manejo de la enfermedad inflamatoria intestinal, una enfermera y un paciente. Se propusieron y consensuaron posicionamientos sobre el manejo de la PUR.Resultados: La RS incluyó 43 artículos de calidad baja-moderada. Cerca del 30% de los pacientes presentaban PUR y su impacto en la calidad de vida del paciente es muy relevante. Se objetivaron muchas lagunas de conocimiento relacionadas con las características clínicas y evolución, eficacia, seguridad y selección de los tratamientos farmacológicos de la PUR. Los expertos propusieron 13 posicionamientos que alcanzaron el nivel de acuerdo establecido. Estos abordan el diagnóstico de la PU y PUR, sus objetivos terapéuticos y selección del tratamiento, monitorización, respuesta al tratamiento y el papel de la enfermera.Conclusiones: La PUR es frecuente y puede suponer un gran impacto en el paciente. Se precisan estudios para caracterizar la PUR y la eficacia a largo plazo de sus tratamientos. Los posicionamientos propuestos pretenden cubrir las lagunas de conocimiento en esta enfermedad.

Primary Care is the first point of contact for most patients after the onset of symptoms of inflammatory bowel disease (IBD). Establishing an initial diagnostic process based on compatible symptoms and agreed criteria and referral pathways, depending on the degree of suspicion and the patient's situation, can reduce diagnostic delays. Once the patient is referred to the Digestive specialist and the diagnosis of IBD is established, a treatment and follow-up plan is structured. The management of the patient must be shared with the participation of the family practitioners in the diagnosis and treatment of concomitant or intercurrent pathologies, the recognition of flare-ups or complications (of IBD or treatments), education tasks or adherence control. With the purpose of developing a comprehensive guide on the management of IBD aimed at Primary Care doctors, we have developed this positioning document collaboratively between the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU). (c) 2024 The Author(s). Published by Elsevier Espana S.L.U. and Elsevier Espana S.L.U. on behalf of Sociedad Espanola de Medicos de Atencion Primaria (SEMERGEN). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

OBJECTIVE:Identifying proteomic signatures in treatment-naïve individuals newly diagnosed with inflammatory bowel disease (IBD) may provide insights into the underlying pathophysiological mechanisms of the disease and aid in distinguishing Crohn's disease (CD) from ulcerative colitis (UC). DESIGN:In the discovery phase, label-free quantitative proteomics was performed to analyze proteomic profiles in serum extracellular vesicles (EVs), serum, urine, and intestinal tissue from 100 newly diagnosed IBD patients (50 CD and 50 UC), and 51 healthy controls (HC). Serum candidate biomarkers were validated using ELISA in a separate subset cohort (87 CD, 134 UC, and 99 HC), and immunohistochemistry was performed on biopsies from the discovery cohort to confirm findings. RESULTS:We identified 419 proteins in serum EVs, 468 in serum, 683 in urine, and 2603 in intestinal tissue. ELISA results showed lower levels of TTR and APOC3 and higher levels of ATRN in UC patients compared to HC. Similarly, CD patients showed lower TTR and higher ATRN levels compared to HC. Moreover, serum protein S10A9 was differentially upregulated in CD vs UC. Immunohistochemistry revealed increased PRDX4 and AZU1 expression in the ileum of CD patients, whereas AOFB expression was lower in the ileum of CD and in the left colon of both CD and UC compared to HC. CONCLUSION:This comprehensive proteomic study has identified a set of proteins differentially expressed in IBD, which may contribute to a better understanding of its mechanisms and hold promise as candidate biomarkers. Although these findings are preliminary, they warrant further investigation to evaluate their diagnostic and therapeutic relevance.

Objective: Granulocyte-monocyte apheresis (GMA) has shown to be safe and effective in ulcerative colitis (UC), also in combination with biologics, mainly with anti-TNF. The aim of this study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. Patients and methods: A retrospective study was performed in 12 IBD Units, including all patients with refractory UC or unclassified IBD (IBD-U) who received combined GMA plus UST. The number and frequency of GMA sessions, filtered blood volume and time of each session were registered. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, Creactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. Results: Seventeen patients were included (15 UC, 2 IBD-U; median age 47 years [IQR, 35-61]; 59% male; 53% E3). Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab; 65% were also receiving steroids at baseline. Median partial Mayo score at baseline was 6 (IQR, 5-7) and it significantly decreased after 1 and 6 months (p = 0.042 and 0.007, respectively). Baseline FC significantly decreased after 6 months (p = 0.028) while no differences were found in CRP. During follow-up, 18% patients started a new biologic therapy and 12% required surgery; 64% of patients under steroids were able to discontinue them. Adverse events were reported in one patient. Conclusion: GMA can recapture the response to UST in selected cases of UC after PNR or LOR to this drug. (c) 2024 The Authors. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Abstract Background Despite universal use of mesalazine in ulcerative colitis treatment, many aspects of clinical practice remain unclear or are not even addressed in clinical guidelines, leading to significant variations in mesalazine management among clinicians. We aimed to gather different approaches of mesalazine use in ulcerative proctitis (UP). Methods After discussion of a clinical case, a predefined questionnaire was anonymously answered throughout a series of meetings held at 10 different locations in Spain. Results were categorized according to experience levels and inflammatory bowel disease (IBD) focus. Results 259 IBD treating gastroenterologists were engaged; 84% had <10 years of experience and 25% had a specific focus on IBD. Most participants (84%) manage UP based on clinical symptoms (i.e. fecal urgency). In case of a clinically moderate-severe UP, 81% would initiate treatment with high dose of combined mesalazine, while 11% proposed only suppositories. 60% of participants would assess response at 4 weeks. If clinical remission achieved, 85% would use fecal calprotectin (FC) to assess deep remission. Upon initial failure of combined mesalazine treatment at standard dose, 59% attempt optimizing mesalazine doses, while 38% add beclomethasone dipropionate. Younger physicians without specific focus on IBD prefer modifying mesalazine doses (70.5% vs 37.1%), (P=0,006), whereas more experienced physicians with monographic dedication prefer adding beclomethasone dipropionate (60% vs 29.4%), (P=0,006). For maintenance therapy (oral or topical mesalazine) the most important drivers in therapeutic decision-making were severity of the initial flare (40%) and patient preferences (36%). After a moderate-severe flare of UP, 80% would recommend maintenance therapy with high dose oral mesalazine and 3 suppositories/week. For monitoring, less experienced physicians and those not working in IBD units more frequently relied only on clinical parameters (26.6% vs. 8.7%, p=0.01), using FC to a lesser extent (73% vs. 88%, p=0.1) compared to more experienced and IBD focused physicians. In the case of elevated FC in asymptomatic patients, 49% would prefer to scope, while 47% increase mesalazine dose directly. The preferred high dose of mesalazine was 4g (55%) or 4-5g (44%). 73% would not reduce the dose upon achieving remission. Only 75% actively investigate therapeutic adherence. Conclusion Management of mesalazine in UP patients is highly heterogeneous, and clinical guidelines do not address all issues arising in clinical practice. Nevertheless, clinicians in our setting often use high oral and rectal mesalazine doses for both induction and maintenance and they commonly monitor patients using FC.