Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with a relapsing-remitting course. Cytokine dysregulation plays a central role in its pathogenesis, and biological therapies-such as anti‑TNFα agents, vedolizumab, and anti‑IL‑23 monoclonal antibodies-have improved disease control. However, variability in therapeutic response underscores the need for biomarkers to support personalized treatment strategies. A longitudinal study was conducted in 26 patients with clinical‑remission/mild‑activity CD who were treated with adalimumab over 54 weeks. Serum samples were collected at baseline, week 14, and week 54. Eighteen cytokines were quantified using high‑sensitivity Luminex MAP technology. TNFα values were excluded due to drug interference. Clustering and PERMANOVA analyses were used to explore cytokine profiles and their association with disease activity. Four cytokine clusters were identified: Th1‑like, Th2‑like, Th17‑like, and a mixed inflammatory profile including IL‑1β, IL‑2, IL‑12, IL‑21, and IL‑23. Significant reductions in CDAI, C‑reactive protein (CRP), and fibrinogen were observed during treatment. IL‑2, IL‑10, and CCL20 levels increased significantly in patients with active CD (CDAI ≥ 150). Th1 and Th17 signatures were positively correlated with disease activity. Serum assessment of Th1 (IL‑1β, IL‑7) and Th17 (GM‑CSF) signatures generated ROC curves with an AUC of 0.795, compared with CRP (AUC = 0.686) and fibrinogen (AUC = 0.774). Serum cytokine profiling reveals immunological heterogeneity in CD patients treated with adalimumab and may serve as an exploratory biomarker of disease activity and therapeutic response; however, these findings are hypothesis generating and require validation in larger, independent cohorts before clinical applicability can be established.

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 & AIMS:The availability of biologicals has been associated with a decreased rate of first intestinal resection in patients with Crohn's disease (CD). However, its impact on postoperative recurrence (POR) has received little attention. We aimed to assess time trends in the strategies for the management of postoperative CD and the rate of second surgeries over the past 3 decades. METHODS:Adult patients with CD who had undergone a first ileocolic resection between 1990 and 2020 were identified from the Spanish ENEIDA registry. Patients were grouped by date of surgery as follows: before the biological era ([BB] 1990-2000), in the early biological era ([EB] 2000-2010), and in the widespread biological era ([WB] 2011-2020). RESULTS:A total of 4890 patients were included (23% BB, 38% EB, and 39% WB). A significant increase in medical prevention of POR with both thiopurines (BB, 12%; EB, 47%; and WB, 37%; P < .001) and biological agents (BB, 0%; EB, 9%; and WB, 37%; P < .001) was observed. Medical treatment with biologicals for POR also increased (BB, 35%; EB, 48%; and WB, 43%; P < .001). The cumulative surgical POR-free survival rate at 5 and 10 years was significantly higher in both the EB and WB cohorts as compared with the BB cohort (BB, 92% and 83%; EB, 96% and 90%; WB, 97% and 91%, respectively; P < .001). CONCLUSIONS:Medical prevention for POR after the first intestinal resection for CD increased significantly in the past 2 decades, alongside the use of biologicals to treat POR. These changes were associated with a significant decrease in the cumulative probability of surgical POR.

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.

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.

Abstract Background Anti-TNF availability has been associated with a decrease of first intestinal resections in patients with Crohn’s Disease (CD). However, few studies have evaluated the impact of the availability of biological therapies in the medical management of postoperative CD and its long-term outcomes. We aimed to assess the time trends in the strategies for the management of CD in the postoperative setting after a first intestinal resection and the rate of second surgeries (surgical postoperative recurrence –sPOR-) through the last three decades. Methods Adult patients with CD who underwent a first ileocolic resection with ileocolic anastomosis between 1990 and 2020 and with at least one year of clinical follow-up, were identified from the Spanish ENEIDA registry. Patients in whom ileocolic resection was due to cancer were excluded. Patients were grouped by the date of the first surgery (before biologicals era -BB- 1990-2000; early biological era -EB- 2001-2010; widespread biological era -WB- 2011-2020). Medical prevention for POR was defined as any immunomodulator or biological agent that was started within the first 6 months after the index surgery and maintained for at least 3 months. Treatment for POR was defined as any immunomodulator or biological that was started at least 6 months after index surgery. Surgical POR was defined as a second intestinal resection at least 6 months after the index surgery. Results 4,890 patients who were followed-up for a median of 125 months (IQR 70-204), were included. Baseline characteristics of each cohort are shown in Table 1. A significant increase in the proportion of patients starting medical prevention of POR with thiopurines and biologicals was observed over time as well as in the proportion of patients starting treatment with biologicals. The cumulative incidence of sPOR significantly decreased in both EB and WB cohorts (second surgery-free survival at 3, 5 and 10 years: BB 96%, 92%, 83%; EB 98%, 96%, 90%; WB 98%, 97%, 91%; P=<0.001). In the IPTW propensity model to weight differences for POR risk factors, both biologicals cohorts remained associated with a lower risk of sPOR. Conclusion In the last three decades, we observed a significant increase in the use of medical prevention for POR together with a significant increase in using biologicals to treat POR. These changes resulted in a significant decrease in the cumulative incidence of a second intestinal resection in the long-term.

Abstract Background Postoperative recurrence (POR) in patients with Crohn’s disease (CD) can be prevented with early postoperative use of thiopurines or anti-TNFs. However, the benefit of medical prophylaxis has not been assessed in the long-term. We aimed to assess the risk of a second intestinal resection (surgical POR -sPOR-) for CD according to the use of early medical prevention of POR after a first resection. Methods Adult patients with CD who underwent a first ileocolic resection with ileocolic anastomosis between 2000 and 2020 and had at least one year of clinical follow-up, were identified from the Spanish ENEIDA registry. Medical prevention of POR was defined as any immunomodulator (IMM) or biological agent started within the first 3 months after the ileocolic resection and maintained for at least 3 months. Medical treatment of POR was defined as any IMM or biological agent started at least 6 months after the index surgery. Patients in whom ileocolic resection was due to cancer and those starting IMM or biologicals between 3-6 months, were excluded. sPOR was defined by a second intestinal resection at least 6 months after the first one. Results A total of 3,694 patients were included, of whom 2,274 (62%) started medical prevention (1,499 with IMM, 775 with biologicals). 45% exposed to IMM and 31% to biologicals before the first surgery. 30% had none, 43% had one and 27% more than one risk factor for POR. Perianal disease and penetrating behaviour were significantly more frequent among patients following prevention but active smoking at surgery was among non-prevention group. Median disease duration at first surgery of 42 months (IQR, 6-109) and median follow-up until second resection or last visit of 111 months (IQR, 63-168). Surgical POR occurred in 11% (8% prevention group vs 14% non-prevention group). SPOR-free survival was significantly higher among patients following medical prevention (P=.001). In the Cox regression analysis, medical prevention (HR 0.71, 95%CI 0.58-0.87; P=.001) was the only protective factor of sPOR, whereas having any risk factor (HR 1.58, 95%CI 1.23-2.01; P<.0001), L4 location (HR 1.99, 95%CI 1.62-2.45; P<.0001) and extraintestinal manifestations (HR 1.43, 95%CI 1.15-1.77; P=.001) increased the risk. Conclusion Postoperative medical prevention have additional benefits in the long-term by reducing the incidence of sPOR. Our findings support the use of medical prevention instead of endoscopy-driven strategies at least in patients with risk factors.

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).

Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC) but little is known when it is used as the second anti-TNF. Objectives: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. Design: Retrospective observational study. Methods: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). Results: Overall, 473 UC patients were included (330 IVi and 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4% in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. Conclusion: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.

Abstract Background Biologic dose escalation is associated with increased costs and potential safety concerns; therefore, de-escalation could be considered in patients in remission after dose escalation. However, data on de-escalation outcomes is scarce. Primary aim: To describe the frequency and the evolution after de-escalation of infliximab (IFX), adalimumab (ADA), golimumab (GOL), vedolizumab (VED), and ustekinumab (UST). Secondary: To investigate the durability of dose de-escalation, the factors associated with relapse after de-escalation, and the effectiveness of a re-escalation. Methods Adult patients from ENEIDA registry who previously had their biologic dose escalated, were included. De-escalations (either decreasing the dose or lengthening the interval of administration) were specifically analysed. Survival curves assessing the impact of several variables on clinical relapse were compared using the log-rank test. Predictive factors associated with the risk of relapse after dose de-escalation were assessed by Cox-regression. Results A total of 669 de-escalations from 5,096 previous dose escalations were performed (13%). The incidence rate of dose de-escalation per patient-year of follow-up was: 6% (95% confidence interval [CI]=5.8-6.2%), 9% (7.4-10.7%), 5% (1-9%), 6% (5.4-6.6%), and 3% (2.9-3.1%) in patients receiving IFX, ADA, GOL, VED and UST, respectively (Figure 1). The favourable evolution after dose de-escalation (maintaining remission or response) was: 106/132 (80%) and 131/132 (99%) for IFX; 157/209 (75%) and 208/209 (99%) for ADA; 5/5 (100%) and 5/5 (100%) GOL; 14/16 (88%) and 16/16 (100%) for VED; and 9/12 (75%) and 11/12 (92%) for UST. The probability of maintaining the dose de-escalated at 12 months was: 86%, 86%, 88%, 82%, and 90% for IFX, ADA, GOL, VED and UST, respectively (Figure 2). Predictive factors of relapse after de-escalation were as follows: 1) IFX: previous biologic exposure (Hazard ratio [HR]=2.7, 95%CI=1.1-6.9), and 2) ADA: age at dose de-escalation (HR=1.08, 95%CI=1.02-1.15). Variables associated with the risk of relapse with other biologics could not be identified. Response and remission were recaptured after re-escalation, respectively, in: 11/12 (92%) and 7/12 (58%) for IFX; 22/22 (100%) and 13/22 (59%) for ADA; 1/1 (100%) and 0/1 (0%) for GOL; 2/2 (100%) and 2/2 (100%) for VED; and 1/1 (100%) and 1/1 (100%) for UST. Conclusion In the largest cohort of patients with dose escalation of biologic treatment in real-life, approximately 10% of the patients have a dose de-escalation in the long-term. If carried out, the durability of the de-escalation seems to be high over time. In those who relapse after dose de-escalation, re-escalation of therapy is effective in more than half of the patients.

Abstract Background Proximal Crohn’s disease (CD) location (L4 according to the Montreal Classification) is associated with a more severe course with higher risk of abdominal surgery. However, little is known about the relation with perianal disease. The aim of our study was to investigate the impact of L4 disease location on perianal disease incidence and clinical course. Methods A case-control study was conducted in the prospectively maintained ENEIDA database for all CD with and without L4 location between January 2005 and March 2023. Demographic data, disease characteristics, perianal disease diagnosis and evolution according to biologic therapy and surgery requirement were collected. Demographic data, CD characteristics, perianal disease diagnosis and course were analyzed. Cox proportional hazards and Kaplan-Meier methods were used for the analysis of perianal incidence, and biologic and surgery requirement. Results A cohort of 14022 CD patients were included in the analysis. The mean follow-up duration was 6.4 years (SD 4.9). L4 location showed a lower prevalence of perianal disease (18.0 vs 19.9%, p=0.018), with lower rate of fistulas (60.9 vs 66.1%, p=0.021) and perianal abscesses (33.5 vs 39.4%, p=0.013). Perianal disease and L4 were associated with male sex (OR 1.29, p<0.001), younger age (43 vs 44), and the structuring phenotype (OR 2.14, p<0.001). L4 location was associated with a lower incidence of perianal disease (HR 0.891, p=0.041), while proctitis was associated with a higher risk (HR=2.161, p<0.001). L4 location was also associated with a lower requirement for biologics (HR 0.712, p=0.023), along with advanced age (HR 0.988, p<0.001). Proctitis (HR 1.292) and a history of perianal surgery (3.373) were associated with a higher requirement for biologics. At univariate analysis, L4 location was associated with a lower requirement of surgery (HR 0.833), however at multivariate analysis this finding was not confirmed (p=0.525). Instead, a history of active smoking (HR 1.419), the use of biologics (HR 2.262), and CD penetrating pattern (HR 1.277) were associated with a higher requirement for perianal surgery. Conclusion L4 location is associated with a lower incidence of perianal disease and a more benign course with lower requirement for biologics and surgery.

Abstract Background Aims: 1) To describe the main epidemiological and clinical characteristics of patients at IBD diagnosis and the long-term outcomes; 2) to analyse the use of drugs for IBD, and the need of hospitalisations and surgeries; 3) to compare IBD management based on the type of disease and the resources of the hospitals. Methods Prospective, population-based nationwide registry. Adult patients diagnosed with IBD, Crohn’s Disease (CD), Ulcerative Colitis (UC) or IBD unclassified, during 2017 in the 17 Spanish regions were included. Patients who consented were followed-up for 5 years (yr) after diagnosis. Treatment was grouped into 5 categories: mesalamine (oral or topical), steroids (intravenous, oral, or topical), immunomodulators (thiopurines, methotrexate or cyclosporine), biologics (anti-TNF, vedolizumab, ustekinumab) or JAK inhibitors (JAKi), and surgery. Hospitals were classified into high resources and low resources ones. Cumulative incidence of exposure to each of the studied treatments was estimated by Kaplan-Meier curves; curves were compared with log-rank test. Results 3,301 incident cases of IBD diagnosed during 2017 in 108 hospitals, covering over 22 million inhabitants in Spain (about 50% of the population), were enrolled into the follow-up study. Main characteristics of the cohort are summarised in table 1. Median diagnosis delayed was 3.5 months (5.6 in CD and 2.7 in UC, p<0.001). During the 5-yr follow-up, 25% of UC patients progressed to more extensive involvement, while 8% of CD patients with inflammatory behaviour progressed to either stricturing or fistulising behaviour. Most of the patients who received mesalamine, corticosteroids, or immunomodulators initiated treatment within the first 2 years after diagnosis (figure 1). However, the cumulative incidence of biologics/JAKi usage steadily increased over time, reaching 49% by the 5-yr timepoint in CD. In terms of surgeries, a progressive increase in cumulative incidence was observed in CD; the incidence of colectomy remained stable in UC from the 2nd year post-diagnosis. A higher cumulative incidence of biologics/JAKi usage, hospitalisations, and surgeries was observed in CD at high resources hospitals; no differences were observed in the use of other therapeutic resources or the management of UC. Conclusion In the EpidemIBD large-scale epidemiological study, we have observed that the delay in diagnosing IBD is shorter than previously described. Approximately 50% of patients with CD and 20% of patients with UC ended up receiving biologics/JAKi in the first 5 yrs following diagnosis. The percentage of patients undergoing surgery was lower than previously reported; in the case of UC, the majority of colectomies occurred within the first 2 yrs after diagnosis.

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. A univariate Cox regression analysis assessed the association of disease location with biologic use and persistence (with treatment discontinuation as a failure event), as well as the use of intestinal resections. A multivariate model was constructed to evaluate the independent association of disease location with therapeutic patterns, controlling for potential confounders such as sex, age at inclusion and diagnosis, disease duration and behavior, previous surgery or biological therapy, extraintestinal manifestations, and perianal disease. RESULTS:The study included 17,292 patients with a median follow-up period of 6 years (interquartile range 2-10 years). Ileocolonic location was associated with a higher biologic use than colonic location (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.22-1.38) and ileal disease (HR 1.21, 95% CI 1.16-1.27), independently predicting biologic use (P < 0.001). Ileal location was associated with a lower biologic persistence than ileocolonic location (HR 1.14, 95% CI 1.07-1.21) and colonic disease (HR 1.10, 95% CI 1.01-1.20), independently predicting biologic persistence (P = 0.019). Ileal disease was associated with a higher likelihood of intestinal resections than colonic (HR 2.82, 95% CI 2.45-3.25) and ileocolonic location (HR 1.13, 95% CI 1.05-1.22), independently predicting the use of surgery (P < 0.001). DISCUSSION:CD location with ileal predominance is associated with a distinct therapeutic pattern, including higher biologic use, lower treatment persistence, and increased rates of intestinal resections.

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. Familial forms were defined as those cases with at least one first-degree relative diagnosed with IBD. Disease phenotype, the use of biological agents, or surgical treatments were the main outcomes.Results A total of 5263 patients [2627 Crohn's disease (CD); 2636 ulcerative colitis (UC)] were included, with a median follow-up of 31 months. Of these, 507 (10%) corresponded to familial forms. No clinical differences were observed between familial and sporadic IBD forms except a lower age at IBD diagnosis and a higher rate of males in familial forms of UC. In CD, the proportions of patients treated with thiopurines (54.4% vs 46.7%; P = .015) and survival time free of thiopurines (P = .009) were lower in familial forms. No differences were found regarding the use of biological agents. Concerning surgery, a higher rate of intestinal resections was observed in sporadic CD (14.8% vs 9.9%, P = .027). No differences were observed in UC.Conclusions In the era of biological therapies, familial and sporadic forms of IBD show similar phenotypes and are managed medically in a similar way; whether these is due to lack of phenotypical differences or an effect of biological therapies is uncertain. What is already known on this topic: IBD's etiopathogenesis points to an interaction between environmental and genetic factors, being familial history a controversial prognostic factor. Biological agents use and need for surgery regarding familial or sporadic forms of IBDs present conflicting results. What this study adds: Familial and sporadic forms of IBD have similar phenotypes and are managed medically and surgically in a similar way. How this study might affect research, practice or policy: Familial aggregation should not be considered a factor associated with more aggressive disease.Conclusions In the era of biological therapies, familial and sporadic forms of IBD show similar phenotypes and are managed medically in a similar way; whether these is due to lack of phenotypical differences or an effect of biological therapies is uncertain. What is already known on this topic: IBD's etiopathogenesis points to an interaction between environmental and genetic factors, being familial history a controversial prognostic factor. Biological agents use and need for surgery regarding familial or sporadic forms of IBDs present conflicting results. What this study adds: Familial and sporadic forms of IBD have similar phenotypes and are managed medically and surgically in a similar way. How this study might affect research, practice or policy: Familial aggregation should not be considered a factor associated with more aggressive disease.

SummaryBackgroundUlcerative 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. Our aim was to describe the characteristics of patients with refractory UP and their disease‐related complications, and to identify the need for immunosuppressive therapies.MethodsWe identified patients with UP from the prospective ENEIDA registry sponsored by the GETECCU. We evaluated socio‐demographic data and complications associated with immunosuppression. We defined immunosuppression as the use of immunomodulators, biologics and/or small molecules. We used logistic regression to identify factors associated with immunosuppressive therapy.ResultsFrom a total of 34,716 patients with ulcerative colitis, we identified 6281 (18.1%) with UP; mean ± SD age 53 ± 15 years, average disease duration of 12 ± 9 years. Immunosuppression was prescribed in 11% of patients, 4.2% needed one biologic agent and 1% needed two; 2% of patients required hospitalisation, and 0.5% underwent panproctocolectomy or subtotal colectomy. We identified 0.2% colorectal tumours and 5% extracolonic tumours. Patients with polyarthritis (OR 3.56, 95% CI 1.86–6.69; p < 0.001) required immunosuppressants.ConclusionsAmong patients with refractory UP, 11% required immunosuppressant therapy, and 4.2% required at least one biologic agent.

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. Participants' magnetic resonance findings were analysed considering normal values and thresholds determined in controls with no history of inflammatory bowel disease [n=40], and in patients with Crohn's disease with no history of colonic involvement [n = 12]. Subjects with UC were stratified according to disease duration [< 7 years vs 7‒14 years vs > 14 years]. RESULTS:We analysed 41 subjects with ulcerative colitis [20 women; Mayo endoscopic subscore 0 in 38 [92.7%] and 1 in three [7.3%]]. Paired segment-by-segment comparison of magnetic resonance findings in colonic segments documented as being affected by ulcerative colitis versus controls showed that patients with ulcerative colitis had decreased cross-sectional area [p ≤ 0.0034] and perimeter [p ≤ 0.0005] and increased wall thickness [p = 0.026] in all segments. Colon damage, defined as wall thickness ≥ 3 mm, was seen in 22 [53.7%] patients. Colon damage was not associated with disease duration or quality of life. CONCLUSIONS:Morphological abnormalities in the colon were highly prevalent in patients with ulcerative colitis in the absence of inflammation. Structural bowel damage was not associated with disease duration or quality of life.

Abstract Background Colectomy is still necessary in some patients with inflammatory bowel disease (IBD). The decision of the technique for the restoration of the bowel continuity depends on the characteristics of the patient and whether it is Crohn’s disease (CD) or ulcerative colitis (UC). The options for the reconstruction are proctectomy with an ileoanal reservoir or an ileorectal anastomosis (IRa). The aim of this study is to evaluate the need of a proctectomy with a definitive ileostomy after an ileorectal anastomosis, the associated risk factors and the need for advanced therapies. Methods This retrospective study includes patients with colectomy and IRa from the ENEIDA national registry. Medical treatment offered during the postoperative follow up and the need for a proctectomy and a definitive ileostomy were evaluated according to the type of IBD. Results Of the 394 patients who underwent an IR, 37% had UC and 63% CD with a medium age of 58 years (RIQ 48-68) and a median follow-up after the IR of 174 months (RIQ 70- 266). 17% of UC’s patients and 42% of CD’s patients had associated perianal disease (p<0.001). The cumulative probability for a definitive ileostomy in UC’s patients was 1%, 2%, and 6% at 5, 10 and 20 years respectively and 1%, 3%, and 11% at 5, 10 and 20 years respectively for the CD (p=0.035). Postoperative maintenance treatment with biologicals was left in 45% (44% UC and 47% CD; p=0.28). During follow-up, the probability of starting biological treatment was 8%, 17%, 35% at 2, 5 and 10 years in CD and 3%, 12%, 28% at 2, 5 and 10 years in UC (p=0.59). Conclusion The probability of requiring a definitive ileostomy/proctectomy after an IR is low, although is more frequent in patients with CD than with UC. Because of this low probability an IR is a valid alternative to the reservoir or even to the proctectomy with a definitive ileostomy in selected patients, keeping in mind one third of the patients would need advanced therapies.