New insights into thiopurine toxicity: The contribution of rare XDH variants to myelotoxicity.

Thiopurines (azathioprine and mercaptopurine) are immunosuppressant drugs widely used for the treatment of acute lymphocytic leukemia, organ transplantation and autoimmune diseases, including inflammatory bowel diseases. Thiopurine-induced myelotoxicity (TIM) remains a significant concern in thiopurine therapy, with around 50 % of cases lacking explanation through known genetic variants in thiopurine methyltransferase (TPMT) or nudix (nucleoside diphosphate linked moiety X)-type motif 15 (NUDT15). For these patients, genetic influence remains unknown.

Frequency and Effectiveness of Dose Escalation and De-Escalation of Biologic Therapy in Inflammatory Bowel Disease: The RAINBOW-IBD Study of ENEIDA.

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.

Volumetric Changes in Perianal Fistulizing Crohn's Disease Measured by Magnetic Resonance Is Feasible and Could Be a Potential Biomarker to Predict Clinical Outcomes.

Background And Aim: Changes in 3D volumetry of perianal fistulas in patients with Crohn's disease (CD) measured by MRI could be an imaging biomarker of interest. The objective of the study was to determine the value of volumetric changes in CD perianal fistulas after medical treatment to predict outcomes.

Methods: This is a retrospective single-center pilot study evaluating CD patients with active perianal fistulas who started biological therapy between 2012 and 2021.

Influence of Familial Inflammatory Bowel Disease History on the Use of Immunosuppressants, Biological Agents and Surgery in Patients with Pediatric-Onset of the Disease in the Era of Biological Therapies. Results from the ENEIDA Registry.

Pediatric-onset familial inflammatory bowel disease (IBD) may differ from sporadic pediatric-onset IBD in its genetic and environmental background and may have distinct clinical and therapeutic implications. To evaluate the influence of a positive family history of IBD on the use of medical therapies and surgical interventions in adult patients with pediatric-onset IBD. Retrospective case-control study using the Spanish ENEIDA registry, including adults diagnosed with pediatric-onset IBD since 2006.

Differential effects of tofacitinib on macrophage activation contribute to lack of response in ulcerative colitis patients.

Background And Aims: Tofacitinib, a Janus kinase inhibitor, is approved for the treatment of moderate-to-severe ulcerative colitis. Nonetheless, 40-60% of patients will not respond adequately. The mechanisms underlying responses to tofacitinib remain unknown.

Hematopoietic stem cell transplantation in Crohn's disease: a comprehensive review.

Purpose Of Review: Despite advances in medical therapies for the treatment of Crohn's disease (CD), 20-30% of patients fail to respond to these therapies (i.e. refractory CD).

Ileal Predominance in Crohn's Disease Is Associated With Increased Intestinal Surgery and Biological Therapy Use, With Lower Treatment Persistence.

Introduction: Crohn's disease (CD) varies by location, potentially affecting therapy efficacy and surgery risk, although research on this topic is conflicting. This study aims to investigate the independent association between CD location and therapeutic patterns.

Methods: We analyzed patients with CD diagnosed from January 2005 to May 2023 registered in the nationwide ENEIDA registry.

Clinical Approach to STRIDE-II in Real-Life Settings: Analysis and Practical Recommendations.

Background: We aimed to (1) analyze the applicability of the updated Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations in real-world clinical practice, (2) identify barriers to their implementation, and (3) propose practical measures to overcome these obstacles.

Methods: This qualitative study was based on a survey, a literature review, and expert opinions. Nine inflammatory bowel disease (IBD) experts identified 7 areas likely to be controversial or potential implementation barriers in daily clinical practice: endoscopy, histology, ultrasound, quality of life, biomarkers, symptom control, and patient-reported outcomes (PROs).

Subcutaneous Infliximab Cutoff Points in Patients With Inflammatory Bowel Disease: Data From the ENEIDA Registry.

Background And Aims: Switching from intravenous infliximab (IV-IFX) to subcutaneous biosimilar infliximab (SC-IFX) has been shown to safely maintain clinical remission and increase drug levels in patients with Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to evaluate long-term outcomes after switching from IV-IFX to SC-IFX, including the drug concentration thresholds for maintaining remission and other predictors for loss of response after the switch.

Methods: This multicenter observational study involved CD and UC patients who were in clinical remission for at least 24 weeks and were scheduled to switch from IV-IFX to SC-IFX.

Need for therapeutic escalation in patients with refractory ulcerative proctitis: Results from the PROCU study of the ENEIDA registry.

Background: Ulcerative proctitis (UP) can have a milder, less aggressive course than left-sided colitis or extensive colitis. Therefore, immunosuppressants tend to be used less in patients with this condition. Evidence, however, is scarce because these patients are excluded from randomised controlled clinical trials.

Influence of familial forms of inflammatory bowel disease on the use of immunosuppressants, biological agents, and surgery in the era of biological therapies. Results from the ENEIDA project.

Background And Aims: Familial inflammatory bowel disease (IBD) history is a controversial prognostic factor in IBD. We aimed to evaluate the impact of a familial history of IBD on the use of medical and surgical treatments in the biological era.

Methods: Patients included in the prospectively maintained ENEIDA database and diagnosed with IBD after 2005 were included.

Sex-Related Differences in the Phenotype and Course of Inflammatory Bowel Disease: SEXEII Study of ENEIDA.

Background & Aims: The impact of patient sex on the presentation of inflammatory bowel disease (IBD) has been poorly evaluated. Our aims were to assess potential disparities in IBD phenotype and progression between sexes.

Methods: We performed an observational multicenter study that included patients with Crohn's disease (CD) or ulcerative colitis from the Spanish Estudio Nacional en Enfermedad Inflamatoria intestinal sobre Determinantes genéticos y Ambientales registry.

Magnetic Resonance Imaging Features Indicative of Permanent Colon Damage in Ulcerative Colitis: An Exploratory Study.

Background And Aims: It is uncertain whether ulcerative colitis leads to accumulated bowel damage on cross-sectional image. We aimed to characterise bowel damage in patients with ulcerative colitis using magnetic resonance imaging [MRI], and to determine its relation with duration of disease and the impact on patients' quality of life.

Methods: In this prospective study, patients with ulcerative colitis [UC] in endoscopic remission underwent MRI without bowel cleansing, and completed quality-of-life questionnaires.

Magnetic resonance enterography findings 46 weeks after initiation of biological therapy predict long-term adverse outcomes in Crohn's disease.

Background And Aims: Magnetic resonance enterography (MRE) depicts transmural changes in response to biological treatment for Crohn's disease (CD); however, the long-term prognostic significance of these findings is unknown. The primary objective of this study was to identify findings on MRE 46 weeks after initiating biological treatment that predict adverse long-term outcomes.

Methods: Patients with CD underwent MRE 46 weeks after initiating biological treatment and were prospectively followed for 2 years.

Genetic biomarkers of methotrexate response and safety in Crohn's disease: Data from the Spanish ENEIDA registry.

Aims: Methotrexate (MTX) is used to induce and maintain remission in patients with steroid-dependent Crohn's disease (CD). Despite its proven efficacy, its use is limited due to associated adverse events. Polymorphisms involving folate pathway genes might influence MTX efficacy and toxicity.

Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee.

Autoimmune diseases (ADs) are characterized by loss of immune tolerance, high chronicity, with substantial morbidity and mortality, despite conventional immunosuppression (IS) or targeted disease modifying therapies (DMTs), which usually require repeated administration. Recently, novel cellular therapies (CT), including mesenchymal stromal cells (MSC), Chimeric Antigen Receptors T cells (CART) and regulatory T cells (Tregs), have been successfully adopted in ADs. An international expert panel of the European Society for Blood and Marrow Transplantation and the International Society for the Cell and Gene Therapy, reviewed all available evidence, based on the current literature and expert practices, on use of MSC, CART and Tregs, in AD patients with rheumatological, neurological, and gastroenterological indications.

Controversies in the management of anti-TNF therapy in patients with Crohn's disease: a Delphi consensus.

Background: Despite research, there are still controversial areas in the management of Crohn's disease (CD).

Objective: To establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD.

Methods: Clinical controversies in the management of CD using anti-TNF therapies were identified.

Current status of fertility preservation in a Spanish tertiary public hospital: multidisciplinary approach and experience in over 1500 patients.

Purpose: Currently, 15% of gynaecological and 9% of haematological malignancies are diagnosed before the age of 40. The increased survival rates of cancer patients who are candidates for gonadotoxic treatments, the delay in childbearing to older ages, and the optimization of in vitro fertilisation techniques have all contributed to an increased interest in fertility preservation (FP) treatments. This study reviews the experience of the Fertility Preservation Programme (FPP) of a tertiary public hospital with a multidisciplinary approach.

ADC Values for Detecting Bowel Inflammation and Biologic Therapy Response in Patients With Crohn Disease: A Post Hoc Prospective Trial Analysis.

New biologic agents for Crohn disease (CD) create a need for noninvasive disease markers. DWI may assess bowel inflammation without contrast agents. The purpose of this study was to evaluate ADC values for identifying bowel inflammation and therapeutic response in patients with CD treated with biologic therapy.

De-escalating therapy in inflammatory bowel disease: Results from an observational study in clinical practice.

Background And Objectives: Combination therapy with an immunomodulator (IMM) and an anti-TNF is commonly recommended in Crohn's disease (CD) and ulcerative colitis (UC) patients. However, little is known about relapse rates after therapeutic de-escalation. This study aimed to evaluate the risk of relapse in a cohort of UC and CD patients with long-standing clinical remission after discontinuation of IMM or anti-TNF and to identify predictive factors for relapse.

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.