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.

INTRODUCTION:Subcutaneous (sc) vedolizumab is an alternative to intravenous (iv) vedolizumab for the treatment of patients with mild-to-moderate flares of inflammatory bowel disease (IBD). AIMS:To analyse the persistence rate of the sc vedolizumab and its pharmacokinetics in patients previously treated with iv vedolizumab; describing clinical and biochemical remission rates at one year, and comparing previous intravenous intensification regimens. METHODS:Multicenter, descriptive, observational, and retrospective study of a cohort of 54 patients with IBD treated with iv vedolizumab for more than six months, who were switched to sc vedolizumab under a standard regimen, 32 patients (59%) with a diagnosis of ulcerative colitis (UC) and 22 patients (41%) with Crohn's disease (CD) RESULTS: After one year of follow-up, 93% of the patients continued with vedolizumab, 100% were in clinical remission, and 86% achieved biochemical remission (calprotectin <150). A progressive increase in vedolizumab levels was observed after switching to sc vedolizumab, with statistical significance (p<0.05). 14 patients (25.9%) were on an intensified regimen before switching to sc vedolizumab; however, all patients remained on subcutaneous vedolizumab at a dose of 108 mg every two weeks without the need for intensification. CONCLUSION:After switching to sc vedolizumab in patients with endovenous vedolizumab treatment, high persistence rate at one year of follow-up is achieved, with a greater tendency to biochemical remission, which is more pronounced in previously intensified patients without the need for subcutaneous vedolizumab intensification.

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.

Introducción Vedolizumab vía subcutánea (sc) es una alternativa a vedolizumab vía intravenosa (iv) en el tratamiento de los pacientes con brote leve/moderado de enfermedad inflamatoria intestinal. Objetivos Analizar el porcentaje de persistencia del fármaco vía sc y la farmacocinética en los pacientes en tratamiento con vedolizumab vía iv después de cambiar a vedolizumab vía sc describiendo los porcentajes de remisión clínica y bioquímica al año, comparando regímenes previos de intensificación vía iv. Métodos Estudio multicéntrico, descriptivo, observacional y retrospectivo de una cohorte de 54 pacientes con enfermedad inflamatoria intestinal en tratamiento con vedolizumab vía iv durante más de 6 meses, a los que se les realizó un cambio a vedolizumab vía sc en régimen estándar, 32 pacientes (59%) con diagnóstico de colitis ulcerosa y 22 pacientes (41%) con enfermedad de Crohn. Resultados Al año de seguimiento, el 93% de los pacientes seguían con vedolizumab, el 100% estaban en remisión clínica y un 86% alcanzaron remisión bioquímica (calprotectina <150). Se evidenció un aumento progresivo de los niveles de vedolizumab tras el cambio a vedolizumab vía sc con significación estadística (p<0,05). Catorce pacientes (25,9%) estaban en un régimen intensificado antes de cambiar a vedolizumab vía sc; no obstante, todos los pacientes se mantuvieron con vedolizumab vía sc a dosis de 108 mg/2 semanas sin necesidad de intensificación. Conclusión Tras el cambio a vedolizumab vía sc en los pacientes en tratamiento con vedolizumab vía iv, se consigue una alta persistencia del fármaco al año, con una mayor tendencia a la remisión bioquímica, que es más acusada en los pacientes previamente intensificados sin necesidad de intensificar vedolizumab vía sc.

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.

Objective: The recommendations of the Spanish Ministry of Health on vaccination in risk groups include mesalazine among the treatments with a possible negative effect on its effectiveness. However, this is not the recommendation of most experts. Our objective was to evaluate the effect of mesalazine on the humoral response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease (IBD). Methods: VACOVEII is a Spanish, prospective, multicenter study promoted by GETECCU, which evaluates the effectiveness of the SARS-CoV-2 vaccine in patients with IBD. This study includes IBD patients who have recieved the full vaccination schedule and without previous COVID-19 infection. Seroconversion was set at 260 BAU/mL (centralized determination) and was assessed 6 months after full vaccination. In this subanalysis of the study, we compare the effectiveness of the vaccine between patients treated with mesalazine and patients without treatment. Results: A total of 124 patients without immunosuppressive therapy were included, of which 32 did not receive any treatment and 92 received only mesalazine. Six months after full vaccination, no significant differences are observed in the mean concentrations of IgG anti-S between both groups. In the multivariate analysis, antibody titers were independently associated with the use of mRNA vaccines and with SARS-CoV-2 infection. Conclusion: Mesalazine does not have a negative effect on the response to SARS-CoV-2 vaccines in IBD patients. (c) 2024 Elsevier Espana, a, S.L.U. All rights reserved.

Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn’s disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment.

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.

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.

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 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.Results Two hundred and twenty patients were included (74 UC [34%] and 146 CD [66%]). IV-IFX was administered for 52.5 months (range 25-89). Before switch, 106 (49%) patients were receiving intensified IV-IFX. While SC-IFX levels significantly increased following the switch from IV-IFX to SC-IFX, clinical parameters, C-reactive protein, and fecal calprotectin remained unchanged during follow-up. SC-IFX levels were significantly higher in patients receiving the standard IV-IFX dose than in those receiving the intensified dose. Immunomodulatory therapy at baseline and perianal disease had no effect on IFX trough levels, whereas higher body mass index was associated with increased levels. The suggested optimal SC-IFX cutoff concentration for clinical and biochemical remissions based on receiver operating characteristic analysis was 12.2 mu g/mL (area under the curve [AUC]: 0.62) at Week 12 and 13.2 mu g/mL (AUC: 0.57) at Week 52. Drug persistence was 92% at Week 52, with a good safety profile.Conclusions Switching from IV-IFX to SC-IFX safely maintains long-term remission in patients with CD and UC. In maintenance, the optimal cutoff point associated with remission was 12-13 mu g/mL.

Backgroundsome patients with inflammatory bowel disease (IBD) treated with antiTNF develop drug-induced psoriasis (antiTNF-IP). Several therapeutic strategies are possible.Aimsto assess the management of antiTNF-IP in IBD, and its impact in both diseases.Methodspatients with antiTNF-IP from ENEIDA registry were included. Therapeutic strategy was classified as continuing the same antiTNF, stopping antiTNF, switch to another antiTNF or swap to a non-antiTNF biologic. IP severity and IBD activity were assessed at baseline and 16, 32 and 54 weeks.Results234 patients were included. At baseline, antiTNF-IP was moderate-severe in 60 % of them, and IBD was in remission in 80 %. Therapeutic strategy was associated to antiTNF-IP severity (p < 0.001). AntiTNF-IP improved at week 54 with all strategies, but continuing with the same antiTNF showed the worst results (p = 0.042). Among patients with IBD in remission, relapse was higher in those who stopped antiTNF (p = 0.025). In multivariate analysis, stopping antiTNF, trunk and palms and soles location were associated with antiTNF-IP remission; female sex and previous surgery in Crohn´s disease with IBD relapse.Conclusionskin lesions severity and IBD activity seem to determine antiTNF-IP management. Continuing antiTNF in mild antiTNF-IP, and swap to ustekinumab or switch to another antiTNF in moderate-severe cases, are suitable strategies.