Correlation Between Anti-TNF Serum Levels and Endoscopic Inflammation in Inflammatory Bowel Disease Patients.

OBJECTIVES: (a) To evaluate the diagnostic accuracy of anti-TNF trough levels to predict mucosal healing in inflammatory bowel disease (IBD); (b) to determine the best cut-off point to predict mucosal healing in IBD patients treated with anti-TNF. METHODS: This is a multicenter, prospective study. IBD patients under anti-TNF treatment for at least 6 months that had to undergo an endoscopy were included. Mucosal healing was defined as: Simple endoscopic score for Crohn's Disease < 3 for Crohn's disease (CD), Rutgeerts score < i2 for CD in postoperative setting, or Mayo endoscopic score ≤ 1 for ulcerative colitis (UC). Anti-TNF concentrations were measured using SMART ELISAs at trough. RESULTS: A total of 182 patients were included. Anti-TNF trough levels were significantly higher among patients that had mucosal healing than among those who did not. The area under the curve of infliximab for mucosal healing was 0.63 (best cutoff value 3.4 µg/mL), and for adalimumab 0.60 (best cutoff value 7.2 µg/mL). In the multivariate analysis, having anti-TNF drug levels above the cutoff values [odds ratio (OR) 3.1]) and having UC instead of CD (OR 4) were associated with a higher probability of having mucosal healing. Additionally, the need for an escalated dosage (OR 0.2) and current smoking habit (OR 0.2) were also associated with a lower probability of mucosal healing. CONCLUSIONS: There was an association between anti-TNF trough levels and mucosal healing in IBD patients; however, the accuracy of the determination of infliximab and adalimumab concentrations able to predict mucosal healing was suboptimal.

Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) and the Association of Crohn's Disease and Ulcerative Colitis Patients (ACCU) in the management of psychological problems in Inflammatory Bowel Disease patients. / Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) y de la Confederación de Asociaciones de Enfermedad de Crohn y Colitis Ulcerosa (ACCU) para el manejo de los aspectos psicológicos en la enfermedad inflamatoria intestinal.

AIMS: To establish recommendations for the management of psychological problems affecting patients with inflammatory bowel disease (IBD). METHODS: A meeting of a group of IBD experts made up of doctors, psychologists, nurses and patient representatives was held. The following were presented: 1) Results of a previous focal group, 2) Results of doctor and patient surveys, 3) Results of a systematic review of tools for detecting anxiety and depression. A guided discussion was then held about the most important psychological and emotional problems associated with IBD, appropriate referral criteria and situations to be avoided. The validated instrument most applicable to clinical practice was selected. A recommendations document and a Delphi survey were designed. The survey was sent to the group and to a scientific committee of the GETECCU group in order to establish the level of agreement with these recommendations. RESULTS: Fifteen recommendations were established linked to 3 key processes: 1) What steps should be taken to identify psychological problems at an IBD appointment; 2) What are the criteria for referring patients to a mental health specialist; 3) How to approach psychological problems. CONCLUSIONS: Resources should be made available to healthcare professionals so that they can treat these problems during consultations, identify the disorders which could affect the clinical course of the disease and determine their impact on the patient's life in order that these can be treated and followed up by the most suitable professional. These recommendations could serve as a basis for redesigning IBD services or processes and as justification for the training of healthcare personnel.

Psoriasis induced by antiTNF therapy in inflammatory bowel disease: Therapeutic management and evolution of both diseases in a nationwide cohort study.

BACKGROUND: some patients with inflammatory bowel disease (IBD) treated with antiTNF develop drug-induced psoriasis (antiTNF-IP). Several therapeutic strategies are possible. AIMS: to assess the management of antiTNF-IP in IBD, and its impact in both diseases. METHODS: patients 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. RESULTS: 234 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. CONCLUSION: skin 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.

Trends in Targeted Therapy Usage in Inflammatory Bowel Disease: TRENDY Study of ENEIDA.

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.

Management and Long-term Outcomes of Crohn's Disease Complicated with Enterocutaneous Fistula: ECUFIT Study from GETECCU.

BACKGROUND AND AIMS: Crohn's disease [CD] can develop penetrating complications at any time during the disease course. Enterocutaneous fistulae [ECF] are disease-related complications with an important impact on quality of life. Our aim was to describe the outcomes of this complication, including its medical and/or surgical management and their temporal trends. The primary endpoint was fistula closure, defined as the absence of drainage, with no new abscess or surgery, over the preceding 6 months. METHODS: Clinical information from all adult patients with CD and at least one ECF-excluding perianal fistulae-were identified from the prospectively-maintained ENEIDA registry. All additional information regarding treatment for this complication was retrospectively reviewed. RESULTS: A total of 301 ECF in 286 patients [January 1970-September 2020] were analysed out of 30 088 records. These lesions were mostly located in the ileum [67%] and they had a median of one external opening [range 1-10]. After a median follow-up of 146 months (interquartile range [IQR], 69-233), 69% of patients underwent surgery. Fistula closure was achieved in 84%, mostly after surgery, and fistula recurrence was uncommon [13%]. Spontaneous and low-output fistulae were associated with higher closure rates (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.17-1.93, p = 0.001, and HR 1.49, 95% CI 1.07-2.06, p = 0.03, respectively); this was obtained more frequently with medical therapy since biologics have been available. CONCLUSIONS: ECF complicating CD are rare but entail a high burden of medical and surgical resources. Closure rates are high, usually after surgery, and fistula recurrence is uncommon. A significant proportion of patients receiving medical therapy can achieve fistula closure.

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients.

BACKGROUND: Previous studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. METHODS: Prospective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. RESULTS: We included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. CONCLUSIONS: Compared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.

Self-expandable metal stents for relieving malignant colorectal obstruction: short-term safety and efficacy within 30 days of stent procedure in 447 patients.

BACKGROUND: The self-expandable metal stent (SEMS) can alleviate malignant colonic obstruction and avoid emergency decompressive surgery. OBJECTIVE: To document performance, safety, and effectiveness of colorectal stents used per local standards of practice in patients with malignant large-bowel obstruction to avoid palliative stoma surgery in incurable patients (PAL) and facilitate bowel decompression as a bridge to surgery for curable patients (BTS). DESIGN: Prospective clinical cohort study. SETTING: Two global registries with 39 academic and community centers. PATIENTS: This study involved 447 patients with malignant colonic obstruction who received stents (255 PAL, 182 BTS, 10 no indication specified). INTERVENTION: Colorectal through-the-scope SEMS placement. MAIN OUTCOME MEASUREMENTS: The primary endpoint was clinical success at 30 days, defined as the patient's ability to maintain bowel function without adverse events related to the procedure or stent. Secondary endpoints were procedural success, defined as successful stent placement in the correct position, symptoms of persistent or recurrent colonic obstruction, and complications. RESULTS: The procedural success rate was 94.8% (439/463), and the clinical success rates were 90.5% (313/346) as assessed on a per protocol basis and 71.6% (313/437) as assessed on an intent-to-treat basis. Complications included 15 (3.9%) perforations, 3 resulting in death, 7 (1.8%) migrations, 7 (1.8%) cases of pain, and 2 (0.5%) cases of bleeding. LIMITATIONS: No control group. No primary endpoint analysis data for 25% of patients. CONCLUSION: This largest multicenter, prospective study of colonic SEMS placement demonstrates that colonic SEMSs are safe and highly effective for the short-term treatment of malignant colorectal obstruction, allowing most curable patients to have 1-step resection without stoma and providing most incurable patients minimally invasive palliation instead of surgery. The risk of complications, including perforation, was low.

Effects of anti-TNF-alpha therapy on hemoglobin levels and anemia in patients with inflammatory bowel disease.

BACKGROUND: Tumor necrosis factor-α (TNF-α) is involved in inducing inflammatory anemia. The potential effect of anti-TNF-α agents on anemia in inflammatory bowel diseases (IBD) is still unknown. METHODS: Analytical data and disease characteristics from 362 IBD patients [271 CD/91UC) treated with anti-TNF-α drugs were retrospectively collected. Effects on disease activity, blood markers and prevalence of anemia were assessed after 6 and 12 months of therapy. RESULTS: 29.3% patients presented anemia at baseline, and significantly reduced to 14.4% and 7.8% after 6 and 12 months of therapy, respectively. Mean ±â€¯SD Hb levels increased significantly at month 6, and this increase was sustained at 12 months. Serum markers of iron metabolism increased significantly compared to baseline, as disease activity measured by C-reactive protein (CRP) was reduced. All these effects were observed independently for CD and UC, and were independent of iron supplementation during treatment. Anemia at baseline (OR 4.09; 95%CI 1.98-8.45) and elevated CRP (OR 3.45; 95CI 1.29-9.22) were independently associated with risk of persistent anemia, as well as iron replacement during therapy (OR 4.36; 95%CI 2.07-9.16). CONCLUSIONS: Controlling disease activity with anti-TNF- α therapy significantly and independently associated with resolution of anemia in IBD, with no relevant role for iron replacement therapy.

Fecal calprotectin is not superior to serum C-reactive protein or the Harvey-Bradshaw index in predicting postoperative endoscopic recurrence in Crohn's disease.

BACKGROUND: Fecal calprotectin (FC) is a widely used noninvasive marker of gut inflammation that is associated with endoscopic severity in Crohn's disease (CD). However, FC has been inconsistent in predicting postoperative recurrence of CD, and its utility in the postoperative setting remains unclear. MATERIALS AND METHODS: Blood and fecal samples were collected in consecutively recruited patients with CD who had undergone ileocolonic resection and required a colonoscopy to assess postoperative recurrence, as defined by the Rutgeerts score (RS). RESULTS: A total of 86 patients were prospectively recruited at five centers. Overall, 49 (57%) had CD recurrence (RS≥i2). FC concentrations trended to increase with RS severity; FC median (interquartile range) was significantly higher in patients with endoscopic recurrence than those in endoscopic remission [172.5 (75-375) vs. 75 (36.5-180.5) µg/g, respectively]. The same occurred for C-reactive protein (CRP) [0.5 (0.1-0.95) vs. 0.1 (0.02-0.27)] mg/dl and the Harvey-Bradshaw index (HBI) [4 (2-7) vs. 1 (0-3.5)]. The three variables significantly correlated. The area under the curve to discriminate between patients in endoscopic remission and recurrence was 0.698 for FC, with 62 µg/g being the optimal cut-off point. This indicated FC would have 85.7% sensitivity and 45.9% specificity in detecting any recurrence, having positive predictive value and negative predictive value of 67.7 and 70.8%, respectively. Area under the curve for CRP and HBI were both 0.710. The combination of CRP and HBI provided a positive predictive value 95.7 and a diagnostic odds ratio of 30.8. CONCLUSION: FC is not better than CRP combined with HBI to predict endoscopic postoperative recurrence of CD.

Short and long-term effectiveness and safety of vedolizumab in inflammatory bowel disease: results from the ENEIDA registry.

BACKGROUND: Effectiveness of vedolizumab in real world clinical practice is unknown. AIM: To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD). METHODS: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response. RESULTS: 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent. CONCLUSIONS: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.

Anemia at the time of diagnosis of inflammatory bowel disease: Prevalence and associated factors in adolescent and adult patients.

BACKGROUND: The prevalence, characteristic and determinants of anemia, at the time of inflammatory bowel disease (IBD) diagnosis have yet to be fully elucidated. METHODS: Retrospective cross-sectional study. Analytical data and disease characteristics obtained upon diagnosis of 1278 IBD patients [Crohn's disease/ulcerative colitis (CD/UC): 718/560] were collected. RESULTS: Anemia was present in 41.2% of patients at diagnosis (47% and 33.8% of CD and UC patients, respectively; p<0.001), being severe in 5.5%. Iron deficiency anemia represented 69.6% of cases, with no differences between CD and UC. Female sex was the strongest risk factor for anemia in both CD and UC (OR 7.11; 95%CI 4.18-12.10 and 6.55; 95%CI 3.39-12.63, respectively), followed by elevated (≥2mg/dL) C-reactive protein (OR 4.08; 95%CI 2.39-6.97 and 4.58; 95%CI 2.26-9.27, respectively). Current smoking was a risk factor for anemia in CD (OR 2.23; 95%CI 1.24-4.02), but a protective one in UC (OR 0.36; 95%CI 0.14-0.92). A penetrating CD behavior increased the risk of anemia (OR 3.34; 95%CI 1.36-8.21); in UC, anemia increased with disease extension (E2+E3) (OR 1.80; 95%CI 1.13-2.86). CONCLUSIONS: Female sex and disease activity are major determinants of anemia at IBD diagnosis. Anemia is associated with disease behavior in CD and with disease extension in UC.

Epidemiology and temporal trends (2000-2012) of inflammatory bowel disease in adult patients in a central region of Spain.

BACKGROUND AND AIM: A growing incidence of inflammatory bowel disease (IBD) has been reported recently in southern Europe, with records of pediatric cases confirming these tendencies in Spain. Data on adult populations, however, have not been provided for over 10 years and need to be updated. PATIENTS AND METHODS: A multicenter retrospective registry of all adult patients with a diagnosis of IBD, including both Crohn's disease (CD) and ulcerative colitis (UC), attending five public hospitals covering a population of 514 368 inhabitants, was assessed. RESULTS: In 2012, the prevalence of CD and UC in adults was 137.17/100 000 inhabitants (95% confidence interval 114-160) and 99.84/100 000 inhabitants (95% confidence interval 79-119), respectively. The mean incidence rate during the period 2000-2012 of CD and UC was 8.9 and 5.6/100 000 inhabitants per year, respectively. Most of our patients (75.55%) had been diagnosed during the last 13 years. CD affected both sexes equally; a trend toward a progressive increase in the age at diagnosis, ileal location, and inflammatory behavior was documented for CD patients. In contrast, UC affected male patients with a higher frequency (57.8%; P=0.015), specifically those older than 40 years of age. Age at UC onset tended to increase progressively from 2000 to 2012 (P<0.001), but the extension on the disease remained unchanged. CONCLUSION: IBD is a highly prevalent disorder in our region, reaching the incidence of CD similar to the figures provided for Northern Europe. Changes in IBD localization, behavior, and age at diagnosis were documented during the period 2000-2012.