Fernando Gomollón

Aims: This study aimed to describe the characteristics of newly diagnosed inflammatory bowel disease (IBD) patients and to analyse their clinical course within the first 5 years after diagnosis, including the need for surgery, hospitalisations and treatments. Methods: This prospective and large multicentre incident cohort registry in Spain enrolled adults diagnosed with Crohn's disease (CD), ulcerative colitis (UC) or unclassified IBD (IBD‐U) in 2017 and followed them for 5 years. Results: A total of 3301 patients were enrolled: 1526 with CD, 1633 with UC and 142 with IBD‐U. Their median age at diagnosis was 43 years (interquartile range 31–56) and approximately 50% were male. Within 5 years post‐diagnosis, 30% received biologics or JAK inhibitors (JAKi), 34% were hospitalised at least once and 9% underwent surgery. The cumulative incidence of biologic/JAKi treatment, hospitalisations and surgeries was higher among CD patients. Use of biologics/JAKi correlated with a more aggressive CD phenotype, greater UC extent and younger age at diagnosis. Biologics/JAKi treatment was associated with lower hospitalisation risk in both CD (Hazard ratio [HR] = 0.4, 95% confidence interval [CI] = 0.2–0.6) and UC patients (HR = 0.5, 95% CI = 0.2–0.9). However, it was not associated with the risk of abdominal surgery in CD but was linked to an increased risk of surgery in UC (HR = 11.9, 95% CI = 4.6–30.4). Conclusions: This large multicentre cohort demonstrated a higher use of biologics/JAKi during the first 5 years after IBD diagnosis than previously reported. Treatment with biologics/JAKi was associated with reduced risk of hospitalisation. However, under current clinical practice patterns, this therapeutic approach did not translate into lower risk of abdominal surgery.

The Spanish Working Group on Crohn’s Disease and Ulcerative Colitis (GETECCU) was founded in 1990 to improve the clinical care and scientific knowledge of inflammatory bowel disease (IBD) in Spain. From its origins as a clinician-driven collaborative network, GETECCU has developed into a nationally and internationally recognised platform, supporting multicentre research, quality assurance and medical education in IBD. A key achievement has been the development of ENEIDA (Estudio Nacional en Enfermedad Inflamatoria Intestinal sobre Determinantes Genéticos y Ambientales), a nationwide prospective registry that now includes data from over 100 centres and more than 85,000 patients. ENEIDA has supported a wide range of observational studies and translational projects and has become a cornerstone of Spanish IBD research. Complementing this scientific foundation, the Certification of Units of Excellence programme for certifying IBD units – launched in 2017 – has promoted equity, quality and benchmarking of care. More than 80 units across the country are currently accredited under this system. GETECCU has also prioritised generational renewal through the GETECCU Young Group, which fosters early-career leadership in research and education. In parallel, the society has expanded its international presence, participating in ECCO and Pan-American Crohn’s and Colitis Organisation, and co-leading the Five Nations initiative together with peer groups in France, Italy, Israel and Portugal. This article presents an overview of GETECCU’s structure, current status and strategic directions. Looking ahead, GETECCU aims to promote research of excellence, continuous education through the translation of scientific knowledge into clinical practice, equitable access to specialised care across regions and the advancement of integrated multidisciplinary care models. GETECCU represents a well-established example of how a national academic group can evolve into a driver of innovation and quality in IBD.

Background and Objectives: Crohn’s Disease (CD) is a chronic inflammatory condition often treated with anti-TNF agents such as infliximab (IFX) and adalimumab (ADA). This study compares the efficacy, immunogenicity, and pharmacokinetics of IFX and ADA over a 54-week period. Materials and Methods: A prospective, multicentre cohort study was conducted involving 72 patients with active CD (Crohn’s disease activity index, CDAI > 150), who received treatment with either IFX (n = 42) or ADA (n = 30). Results: By week 54, treatment discontinuation occurred in 31% of IFX-treated patients (13/42) and 37% of ADA-treated patients (11/30), with no significant difference between groups (p = 0.612). Among those who completed the study, clinical remission (CDAI ≤ 150) was achieved in 65% of the IFX group and 95% of the ADA group (OR = 8.10; 95% CI = 1.10–20.11; p = 0.049). Loss of clinical response was more frequent in the IFX group (31%) than in the ADA group (10%), with an OR of 0.25 (95% CI: 0.06–0.97; p = 0.045). Fibrinogen levels declined in both groups, with a greater reduction observed in ADA-treated patients. The area under the ROC curve (AUC) for fibrinogen in distinguishing remission from active disease was 0.608 for IFX and 0.711 for ADA. Anti-drug antibodies were detected more frequently in IFX-treated patients (16.7%, 7/42) compared to those receiving ADA (6.7%, 2/30). Conclusions: Treatment with ADA demonstrated superior efficacy compared to IFX in maintaining clinical remission in CD, which was paralleled by a more effective normalization of fibrinogen levels (Clinical trial: GET-CRO-2010-01).

Galectin-1 and -9 (Gal1/9) are essential mediators of immune-inflammatory responses, which makes these proteins potential biomarkers for immune-mediated diseases (IMIDs), such as rheumatoid arthritis (RA), psoriasis (PS), psoriatic arthritis (PsA), inflammatory bowel disease, and systemic lupus erythematosus (SLE). Our aim was to evaluate plasma Gal1/9 differences between IMID patients and healthy donors (HD). We analyzed 980 plasma samples divided into two analytical cohorts (600 discovery group and 380 validation group). Generalized linear models estimated Gal1/9 levels, adjusting for sex, age, storage time, and plate variability. In the overall IMID group, plasma Gal1 levels were comparable to those of HD, while Gal9 levels were significantly elevated. Levels varied across individual diseases: SLE patients consistently showed the highest Gal1/9 levels compared to both HD and other IMIDs, and RA patients had elevated Gal9 levels versus HD. Both Gal1 and Gal9 plasma levels correlated positively with higher disease activity, and Gal1 was higher in patients with longer disease duration. After adjustment for these confounders, SLE and RA patients maintained the highest Gal9 levels compared to HD. Our study demonstrates that Gal1 and Gal9 are differentially expressed across IMIDs, with particularly elevated levels in SLE, and both galectins are associated with disease activity.

Background: 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. Objective: 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. Methods: Retrospective case–control study using the Spanish ENEIDA registry, including adults diagnosed with pediatric-onset IBD since 2006. Familial forms (FFs) (defined by a first-degree relative with IBD) and sporadic forms (SF) (with no relatives of any grade with IBD) were matched 1:4 by type of IBD, sex, age at IBD diagnosis, disease location, disease pattern, development of perianal disease and smoking status at diagnosis. The study outcomes were the use of immunomodulators, biological therapies, intestinal surgery, and perianal surgery during follow-up. Results: Six-hundred and fifty-five Crohn’s disease (CD) (131 FF) and 440 ulcerative colitis (UC) (88 FF) patients were included. Immunomodulators, biological therapy, and intestinal surgery were used evenly among FF and SF patients for both UC and CD. However, a higher requirement for perianal surgery among FF-CD patients (18.3% vs. 10.5%, p = 0.014), together with a shorter time to perianal surgery (11 vs. 20 months, log-rank p = 0.004), was observed. Conclusions: Patients with FF of pediatric-onset IBD do not exhibit an increased use of immunomodulators, biological agents, or intestinal surgery, but do exhibit a higher need for perianal surgery, as compared to patients with SF pediatric-onset IBD.

Background: As part of the IBD Character initiative, we examined an inception cohort and investigated mucosal microbiota composition and transcriptional activity in relation to clinical outcomes. Methods: A cohort of 237 individuals were included from five countries: Crohn’s disease (CD, n = 72), ulcerative colitis (UC, n = 57), symptomatic non-IBD controls (SC, n = 78) and healthy controls (HC, n = 30). Rectal/colonic biopsies were obtained at inclusion, and DNA and RNA were extracted from the same biopsy and examined by sequencing the 16S rRNA V4 region. Results: Beta diversity measurements separated IBD from both HC and SC. IBD and SC exhibited reduced intra-individual diversity compared with HC. When comparing taxonomy at DNA and RNA level, six bacteria were found to differ in abundance and/or transcriptional activity between IBD and symptomatic control, while there were 14 and three between symptomatic control and CD and UC, respectively. A limited number of bacterial taxa were responsible for the largest difference between presence and activity, separating patients and controls. Multiple bacterial taxa were associated with treatment escalation in both UC and CD. Machine-learning models separated IBD from symptomatic controls and treatment escalators from non-escalators (AUC > 0.8). However, the differential effects were mainly driven by clinical biomarkers, such as f-calprotectin, s-albumin, and b-hemoglobin. Conclusion: Differences between presence and transcriptional activity were found among multiple taxa when assessing 16S rRNA at DNA and RNA level. Symptomatic controls were more similar to the IBD patients compared to HC. The analyses suggest that the mucosal microbiota carries a moderate diagnostic and predictive potential, outcompeted by f-calprotectin.

Background: HLADQA1*05 is recently associated with heightened immunogenicity to anti-tumor necrosis factor (TNFα). We aimed to determine whether HLADQ1*05 is a risk factor for primary non-response, loss of response (LOR), or adverse events (AE) to first-line anti-TNFα in patients with inflammatory bowel disease. Methods: We performed a retrospective observational study enrolling biologic naïve patients with Crohn’s disease and ulcerative colitis who initiated adalimumab or infliximab from 2000 to 2021. HLA-DQA1 genotype was determined in all patients and immunogenicity in 98 patients. Results: We enrolled 408 patients who started first-line infliximab (n = 211) and adalimumab (n = 197), with a mean follow-up of 7.6 years. Primary response at Week 24 occurred in 347 (85.0%), LOR in 133 (38.3%), and AE in 93 (22.8%). The HLADQA1*05 was identified in 185 (43.3%) patients. In multivariate analyses, no risk factors were identified for primary response. HLADQA1*05 was an independent risk factor for LOR (adjusted hazard ratio [aHR] = 1.80, 95% CI = 1.21-2.67) and immunogenicity (aOR = 3.44, 95% CI = 1.12-11.92). HLADQA1*03 was a protective factor against LOR (aHR = 0.42, 95% CI = 0.20-0.88). Stratified analysis by anti-TNF type showed that HLADQA1*05 increased the risk of LOR to infliximab but not to adalimumab and HLADQA1*03 decreased the risk of LOR to adalimumab but not to infliximab. Female sex, infliximab, and the co-presentation of at least one allele of the HLADQA1*03 and HLADQA1*05 were risk factors for AE. Conclusions: HLADQA1*05 is associated with a higher risk of LOR and immunogenicity, particularly to infliximab. HLADQA1*03 seems to play a protective role against LOR, particularly adalimumab. Female sex and infliximab are risk factors for AE.