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 ENEIDA registry. Data extraction was conducted in July 2021. RESULTS: A total of 51,595 patients with IBD were included, 52% were males and 25,947 had CD. The median follow-up period after diagnosis was 9 years in males and 10 years in females. In CD, female sex was an independent risk factor for medium disease onset (age, 17-40 y) (relative risk ratio, 1.45; 95% CI, 1.31-1.62), later disease onset (age, >40 y) (relative risk ratio, 1.55; 95% CI, 1.38-1.73), exclusive colonic involvement (odds ratio, 1.24; 95% CI, 1.14-1.34), inflammatory behavior (odds ratio, 1.14; 95% CI, 1.07-1.21), and extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.38-1.59). However, female sex was a protective factor for upper gastrointestinal involvement (odds ratio, 0.84; 95% CI, 0.79-0.90), penetrating behavior (odds ratio, 0.76; 95% CI, 0.70-0.82), perianal disease (odds ratio, 0.77; 95% CI, 0.71-0.82), and complications (odds ratio, 0.73; 95% CI, 0.66-0.80). In ulcerative colitis, female sex was an independent risk factor for extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.26-1.61). However, female sex was an independent protective factor for disease onset from age 40 onward (relative risk ratio, 0.76; 95% CI, 0.66-0.87), left-sided colonic involvement (relative risk ratio, 0.72; 95% CI, 0.67-0.78), extensive colonic involvement (relative risk ratio, 0.59; 95% CI, 0.55-0.64), and abdominal surgery (odds ratio, 0.78; 95% CI, 0.69-0.88). CONCLUSIONS: There is sexual dimorphism in IBD. The patient's sex should be taken into account in the clinical management of the disease.

Predictive role of ITPA genetic variants in thiopurine-related myelotoxicity in Crohn's disease patients.

Thiopurines, an effective therapy for Crohn's disease (CD), often lead to adverse events (AEs). Gene polymorphisms affecting thiopurine metabolism may predict AEs. This retrospective study in CD patients (n = 114) with TPMT activity > 5 Units/Red Blood Cells analyzed TPMT (c.238 G > C, c.460 G > A, c.719 A > G), ITPA (c.94 C > A, IVS2 + 21 A > C), and NUDT15 (c.415 C > T) polymorphisms. All patients received azathioprine (median dose 2.2 mg/kg) with 41.2% experiencing AEs, mainly myelotoxicity (28.1%). No NUDT15 polymorphisms were found, 7% had TPMT, and 31.6% had ITPA polymorphisms. AEs led to therapy modifications in 41.2% of patients. Multivariate analysis identified advanced age (OR 1.046, p = 0.007) and ITPA IVS2 + 21 A > C (OR 3.622, p = 0.015) as independent predictors of AEs. IVS2 + 21 A > C was also associated with myelotoxicity (OR 2.863, p = 0.021). These findings suggest that ITPA IVS2 + 21 A > C polymorphism and advanced age predict AEs during thiopurine therapy for CD with intermediate-normal TPMT activity.

Long-term risk of delayed postoperative Crohn's disease recurrence in patients with no or mild endoscopic recurrence at first assessment.

BACKGROUND: Early endoscopic evaluation is recommended for assessment of postoperative recurrence (POR) of Crohn's disease (CD) but no further monitoring recommendations are available. AIM: To evaluate the long-term outcome of patients without endoscopic POR at first endoscopic assessment. METHODS: Retrospective four-centre study including consecutive CD patients with ileocolonic resection (ICR) without endoscopic POR (Rutgeerts score i0-i1) at first endoscopic assessment performed within 18 months from ICR. All patients had a clinical follow-up ≥24 months and at least one further endoscopic assessment. Main outcomes were endoscopic, clinical and surgical POR, need for rescue therapy and "delayed POR" (any need for rescue therapy or clinical or surgical POR) during follow-up. RESULTS: Overall, 183 patients were included (79% with risk factors for POR, 44% without postoperative prophylaxis). Endoscopic POR was observed in 42% of patients. Clinical POR-free survival was 89.4% and 81.5% at 3 and 5 years, and delayed POR-free survival was 76.9% and 63.4% at 5 and 10 years, respectively. In multivariate analysis, postoperative prophylaxis (HR .55; 95% CI .325-.942) and active smoking (HR 1.72; 95%CI 1.003-2.962) were independent risk factors for clinical POR, whereas presence of mild endoscopic lesions at index ileocolonoscopy (i1) was the only risk factor for delayed POR (HR 1.824; 95% CI 1.108-3.002). CONCLUSIONS: Long-term risk of POR among patients with no or mild endoscopic lesions at first ileocolonoscopy after surgery is steadily low, being higher among smokers, in the absence of postoperative prophylaxis and when mild endoscopic lesions are observed in the first endoscopic assessment.

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. We aimed to assess the impact of certain polymorphisms on the therapeutic outcomes of MTX in CD. METHODS: Patients with CD who exclusively followed MTX monotherapy and fulfilled inclusion criteria were identified from the GETECCU ENEIDA registry. Variants of ATIC, DHFR, MTHFR, SLC19A1, ABCB1 and ABCC3 genes were analysed and their association with efficacy and toxicity was assessed. RESULTS: A total of 129 patients were included in the analysis. MTX was used at a median weekly dose of 25 mg (interquartile range, 15-25 mg) and a median time of 14 months (interquartile range, 4-52 months). Thirty-seven percent of the patients achieved disease remission with MTX monotherapy, while 34% were nonresponders (MTX failure). MTX-related toxicity occurred in 40 patients (30%), leading to MTX discontinuation in 19%. DHFR rs408626 (odds ratio [OR] 3.12, 95% confidence interval [CI] 1.22-7.69; P = .017) and MTHFR rs1801133 (OR 2.86, 95% CI 1.23-6.68; P = .015) variants, and smoking (OR 2.61, 95% CI 1.12-6.05; P = .026) were associated with a higher risk of MTX failure. Additionally, the MTHFR rs1801131 variant was associated with a higher risk of MTX-related adverse effects (OR 2.78, 95% CI 1.26-6.13, P = .011). CONCLUSION: Our study shows that variants of MTHFR and DHFR genes may be associated with MTX efficacy and adverse events in patients with CD.

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. 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.

Incidence of herpes zoster in patients with inflammatory bowel disease. / Incidencia de herpes zóster en pacientes con enfermedad inflamatoria intestinal: estudio observacional y retrospectivo en dos hospitales españoles de tercer nivel.

BACKGROUND: Herpes zoster (HZ) is a prevalent disease caused by the reactivation of the varicella-zoster virus (VZV) and associated with chronic morbidity, particularly with post-herpetic neuralgia (PHN). Inflammatory bowel disease (IBD) has been associated with an increased risk of HZ, mainly when immunosuppressive treatment (IMT) is used. However, studies assessing the risk of HZ in IBD are scarce. AIMS: To evaluate the incidence rate and risk factors of HZ in IBD. METHODS: Retrospective study in IBD patients with a positive VVZ serology from two referral hospitals from the area of Barcelona. Diagnosis of HZ and its clinical features were recorded. RESULTS: A total of 398 IBD patients with a positive IgG-VVZ serology were identified. Fifty-eight percent of the patients received IMT (46.5% immunosuppressants monotherapy, 20.6% biologics monotherapy and, 32.7% combination therapy). After a median follow-up of 71 months (IQR 41.5-138.0), 17 (4.3%) patients developed HZ (cumulative incidence of 5.2 per 1000 person-year), 12 of them (70.6%) while receiving IMT. Median age at HZ episode was 38 years (IQR 27.5-52.5). Two (11%) developed PHN. Biological therapy was the only risk factor for developing HZ (OR 3.8 IC 95% 1.3-11.5; p=0.018). CONCLUSIONS: HZ is quite prevalent in IBD, occurring at early ages and particularly among patients using IMT. NPH appears to occur in a notable proportion of cases.

Perception of the impact of intravenous biological treatment on the work and professional environment in patients with inflammatory bowel disease. / Percepción del impacto del tratamiento biológico endovenoso sobre el ámbito laboral y personal en pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: In the treatment of inflammatory bowel disease (IBD), we have biologic therapies administered intravenously and subcutaneously. Recently, some drugs can be administered by either of these routes. The real impact that intravenous administration has on the perception of the disease and the personal and work life of the patient is unknown. METHODS: All IBD patients receiving intravenous infliximab treatment for at least 6 months were anonymously invited to participate. They were provided with a specific structured questionnaire with visual analogue scales (0-10) at two reference centers in the Barcelona area. RESULTS: A total of 90 patients with a median age of 45 years (36-56) and a median infliximab treatment duration of 48 months (24-84) were included. The visit and therapy with infliximab in the day hospital were globally well evaluated (9, IQR 7-10). 78% of patients combined day hospital stays with other activities (26% employment). The personal impact was generally low (4, IQR 0-5.8), but the patient's job was threatened in 43% of patients on intensified treatment. CONCLUSIONS: The intravenous administration of biologic drugs on an outpatient basis is highly satisfactory among IBD patients. The impact on the work sphere appears to be more pronounced than on the personal sphere, an aspect that should be considered in shared decision-making with the patient.

Perception of the need for dietary advice and dietary modifications in inflammatory bowel disease patients. / Percepción de la necesidad de asesoramiento dietético y modificaciones alimentarias en pacientes con enfermedad inflamatoria intestinal.

BACKGROUND AND AIM: In inflammatory bowel disease (IBD), diet can be perceived as a trigger for relapses or clinical worsening, dietary modifications are frequent and not derived from professional advice. The aim of this study was to evaluate the perception of the need for dietary advice in patients with IBD, to know the dietary modifications adopted and, it's effect on IBD. METHODS: An anonymous structured questionnaire with a visual analog scale (0-10) was distributed to consecutive outpatients from our IBD unit. RESULTS: A total of 124 complete the questionnaire (54% ulcerative colitis, 46% Crohn's disease). Mean age was 47±12 years. Dietary advice provided in the clinic was assessed with a median score of 7 (IIC, 4.50-9.00). 40% sought external dietary advice, often during the first year after diagnosis (70%). The most frequent dietary recommendations from an external professional were: dairy free diet (29%), low fat (27%), gluten free (23%), and low fiber (21%). Dietary advice from external source was assessed with a median score of 7.50 (IIC, 5.50-9.50), improving digestive symptoms in 73% of cases. Regarding dietary modifications, 61% excluded some foods (57% permanently) and 11% fasted on their own decision. CONCLUSIONS: IBD patient show a clear need for dietary advice, especially at the time of IBD diagnosis. Early specific and in-depth dietary information would increase patient satisfaction and could prevent the adoption of unjustified exclusion diets.

Duration of smoking cessation in patients with inflammatory bowel disease.

BACKGROUND AND OBJECTIVES: Smoking can worsen inflammatory bowel disease (IBD), although evidence regarding the duration of cessation is scarce. The objectives of the study were to determine the duration of abstinence and identify the characteristics of relapse in IBD patients. PATIENTS AND METHODS: Using the local database of a nationwide registry of patients with IBD, we identified patients who were active smokers at the time of IBD diagnosis and invited them to participate in the study. Patients were asked about their smoking habit and those who were ex-smokers constituted the study cohort. We obtained clinical and smoking-related data of ex-smokers from medical records and telephone interviews. We measured nicotine dependence using the Fagerström Test for Nicotine Dependence (FTND). RESULTS: We enrolled 121 IBD patients who were ex-smokers: 89 patients with Crohn's disease (CD) and 33 patients with ulcerative colitis (UC). The median age at cessation was lower in patients with CD (38 years) than in patients with UC (46 years) (p=0.002). Follow-up time was shorter in CD patients than in UC patients (114 vs. 168 months, p=0.035). No difference was found in the FTND score. Relapse was more common in CD patients (46%) than in UC patients (24%) (p=0.029), although time to first relapse was similar in both groups of patients (12 and 15 months, respectively; p=0.056). Nicotine dependence was the only independent factor associated with relapse. CONCLUSIONS: The risk of smoking relapse was high, especially in CD patients, although their dependence level was similar to that of UC patients.

Clinical and endoscopic outcomes of patients with colonic Crohn's disease treated with 5-aminosalicylates as monotherapy.

BACKGROUND: In spite of the lack of evidence regarding the clinical benefits of oral 5-aminosalicylic acid (5-ASA) compounds in Crohn's disease (CD), these drugs are frequently used in daily clinical practice, particularly for colonic CD. Our aim is to assess the use and clinical outcomes of 5-ASA of those patients with colonic CD treated with 5-ASA as monotherapy. METHODS: Patients diagnosed with isolated colonic CD and treated with 5-ASA but never exposed to immunosuppressants or biologicals were identified from the local databases of five referral centres. A retrospective review of clinical and endoscopic outcomes was performed. RESULTS: Out of 545 patients with isolated colonic CD, 106 (19%) were treated with oral 5-ASA in monotherapy as maintenance therapy. The median follow-up was 144 months (interquartile range [IQR], 48-234). Almost all of the patients (92%) presented an inflammatory pattern and 11% developed perianal disease. Half of the patients had already received 5-ASA at diagnosis, and the median duration of 5-ASA treatment was 107 months (IQR 22.5-187). Endoscopic remission, as defined by the absence of ulcers at the last complete colonoscopy, was observed in 65% of those patients undergoing at least one colonoscopy during follow-up. Male gender and extraintestinal manifestations were associated with a lower likelihood of achieving endoscopic remission. Nine patients required colectomy, but mostly soon after CD diagnosis. CONCLUSIONS: 5-ASA seems to be of benefit in the long-term in one fifth of patients with colonic CD as the only maintenance therapy and should be considered in fragile patients with Crohn's colitis.

The Genetic Diversity and Dysfunctionality of Catalase Associated with a Worse Outcome in Crohn's Disease.

Chronic gut inflammation in Crohn's disease (CD) is associated with an increase in oxidative stress and an imbalance of antioxidant enzymes. We have previously shown that catalase (CAT) activity is permanently inhibited by CD. The purpose of the study was to determine whether there is any relationship between the single nucleotide polymorphisms (SNPs) in the CAT enzyme and the potential risk of CD associated with high levels of oxidative stress. Additionally, we used protein and regulation analyses to determine what causes long-term CAT inhibition in peripheral white mononuclear cells (PWMCs) in both active and inactive CD. We first used a retrospective cohort of 598 patients with CD and 625 age-matched healthy controls (ENEIDA registry) for the genotype analysis. A second human cohort was used to study the functional and regulatory mechanisms of CAT in CD. We isolated PWMCs from CD patients at the onset of the disease (naïve CD patients). In the genotype-association SNP analysis, the CAT SNPs rs1001179, rs475043, and rs525938 showed a significant association with CD (p < 0.001). Smoking CD patients with the CAT SNP rs475043 A/G genotype had significantly more often penetrating disease (p = 0.009). The gene expression and protein levels of CAT were permanently reduced in the active and inactive CD patients. The inhibition of CAT activity in the PWMCs of the CD patients was related to a low concentration of CAT protein caused by the downregulation of CAT-gene transcription. Our study suggests an association between CAT SNPs and the risk of CD that may explain permanent CAT inhibition in CD patients together with low CAT gene and protein expression.

Impact of immunosuppressants on SARS-CoV-2 infection in elderly patients with inflammatory bowel disease.

BACKGROUND: Older age has been reported as a risk factor for severe SARS-CoV-2 disease (COVID-19). The impact of immunosuppressants (IMS) on COVID-19 is still under debate. AIM: To describe the incidence and severity of COVID-19 in elderly patients with inflammatory bowel disease (IBD) in relation to the use of IMS. METHODS: IBD patients over 65 years of age were selected and grouped in terms of IMS use. Confirmed COVID-19, adherence to IST, comorbidities and concomitant non-IBD-related treatments between 1st of March 2020 to 1st of March 2021 were recorded. RESULTS: Out of 418 patients included, 89 (21.3%) were on IMS. Thirty-two patients (7.7%) had COVID-19, 7 of whom were on IMS (7.6% not on IMS vs. 7.9% on IMS; P = 0.933) and 7 (22%) patients died. CONCLUSIONS: Incidence of COVID-19 among elderly IBD patients was similar to that reported in the background population, regardless of the use of IMS.

Changes in the requirement for early surgery in inflammatory bowel disease in the era of biological agents.

BACKGROUND AND AIM: Biological therapies may be changing the natural history of inflammatory bowel diseases (IBDs), reducing the need for surgical intervention. We aimed to assess whether the availability of anti-TNF agents impacts the need for early surgery in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Retrospective, cohort study of patients diagnosed within a 6-year period before and after the licensing of anti-TNFs (1990-1995 and 2007-2012 for CD; 1995-2000 and 2007-2012 for UC) were identified in the ENEIDA Registry. Surgery-free survival curves were compared between cohorts. RESULTS: A total of 7370 CD patients (2022 in Cohort 1 and 5348 in Cohort 2) and 8069 UC patients (2938 in Cohort 1 and 5131 in Cohort 2) were included. Immunosuppressants were used significantly earlier and more frequently in both CD and UC post-biological cohorts. The cumulative probability of surgery was lower in CD following anti-TNF approval (16% and 11%, 22% and 16%, and 29% and 19%, at 1, 3, and 5 years, respectively P < 0.0001), although not in UC (3% and 2%, 4% and 4%, and 6% and 5% at 1, 3, and 5 years, respectively; P = 0.2). Ileal involvement, older age at diagnosis and active smoking in CD, and extensive disease in UC, were independent risk factors for surgery, whereas high-volume IBD centers (in both CD and UC) and immunosuppressant use (in CD) were protective factors. CONCLUSIONS: Anti-TNF availability was associated with a reduction in early surgery for CD (driven mainly by earlier and more widespread immunosuppressant use) but not in UC.

Impact of pain associated with the subcutaneous administration of adalimumab.

BACKGROUND: There is limited information regarding the impact of patients' perception of injection pain on adherence to treatments, specifically in inflammatory bowel disease (IBD) patients. Therefore, we aimed to determine the impact of the pain associated with the subcutaneous administration of adalimumab in patients with IBD treated with the old formulation and the new low-volume/citrate-free formulation. METHODS: A specifically-designed questionnaire was completed by 76 patients with IBD, who started treatment with adalimumab before the availability of the low-volume/citrate-free formulation and were switched to this new formulation. Intensity of pain was measured by using visual analog scales (VAS). RESULTS: A total of 62 patients (82%) experienced injection-related pain with the initial formulation. The perception of pain was associated with a decreased adherence to the treatment (37%), an increase in pre-administration anxiety (25%) or, as a consequence, the patient required someone else to carry out the injection (21%). Younger age was the only factor associated with pain perception. After switching to the new formulation, perception of pain persisted only in 2 patients (3%). Among those who felt pain with the initial formulation, pre-administration anxiety disappeared in 44%; 32% and 42% stated that the new formulation eased adherence and self-administration. CONCLUSIONS: The perception of pain related to the subcutaneous administration of therapy negatively impacts on treatment adherence in IBD patients. Improved formulations for subcutaneous administration of drugs can positively impact patients' convenience and adherence.

Genetic association between CD96 locus and immunogenicity to anti-TNF therapy in Crohn's disease.

The production of antibodies to anti-tumor necrosis factor alpha (TNF) agents is one of the main causes of treatment failure in Crohn's disease (CD). To date, however, the contribution of genetics to anti-TNF immunogenicity in CD is still unknown. The objective of the present study was to identify genetic variation associated with anti-TNF immunogenicity in CD. We performed a two-stage genome-wide association study in a cohort of 96 and 123 adalimumab-treated patients, respectively. In the discovery stage, we identified a genome-wide significant association between the CD96 locus and the production of antibodies to anti-TNF treatment (P = 1.88e-09). This association was validated in the replication stage (P < 0.05). The risk allele for anti-TNF immunogenicity was found to be also associated with a lack of response to anti-TNF therapy (P = 0.019). These findings represent an important step toward the understanding of the immunogenicity-based mechanisms that underlie anti-TNF response in CD.

Development and validation of the QUECOMIICAT questionnaire: a tool to assess disease-related knowledge in patients with inflammatory bowel disease.

INTRODUCTION: adequate knowledge of inflammatory bowel disease (IBD) is essential for a successful patient-centered management of IBD. OBJECTIVE: due to the scarcity of up-to-date tools for measuring IBD literacy, this single-center, prospective study aimed to develop and validate a new questionnaire to assess IBD-related knowledge. MATERIAL AND METHODS: the study included patients followed up at the Crohn-Colitis Care Unit (UACC) at the Hospital Vall d'Hebron (Barcelona, Spain). Patients admitted to the UACC for the first time were subsequently enrolled into a standard IBD educational program. A pilot questionnaire was developed and validated in 92 IBD patients by determining the internal consistency reliability (Cronbach's α test), feasibility, construct validity (correlation with the Crohn's and Colitis Knowledge [CCKNOW] questionnaire and a knowledge visual analog scale [VAS]) and sensitivity (score change before and after a standard IBD educational program). The questionnaire, named "Qüestionari Coneixements Malaltia Inflamatòria Intestinal Catalunya" (IBD-knowledge questionnaire Catalonia) (QUECOMIICAT) was written in Spanish and had 25 items addressing six dimensions: general concepts, clinic, treatment, surgery, habits and social context. RESULTS: the median (interquartile range) completion time was 15 (10-20) minutes and the floor and ceiling effects were 1.1% and 2.1%, respectively. The Cronbach's α coefficient was α = 0.75. QUECOMIICAT significantly correlated with the VAS (rho = 0.34, p < 0.01) and CCKNOW questionnaires (rho = 0.74, p < 0.01). Patient knowledge significantly increased 24 hours after attending a standard IBD educational program and remained statistically significant one month later (Pearson's test-retest correlation coefficient r = 0.81, p < 0.001). CONCLUSION: in conclusion, the QUECOMIICAT questionnaire is a new up-to-date tool to assess IBD-related knowledge with good feasibility and validation results for use in the routine clinical practice.

Serial semi-quantitative measurement of fecal calprotectin in patients with ulcerative colitis in remission.

BACKGROUND: Fecal calprotectin (FC) correlates with clinical and endoscopic activity in ulcerative colitis (UC), and it is a good predictor of relapse. However, its use in clinical practice is constrained by the need for the patient to deliver stool samples, and for their handling and processing in the laboratory. The availability of hand held devices might spread the use of FC in clinical practice. OBJECTIVES: To evaluate the usefulness of a rapid semi-quantitative test of FC in predicting relapse in patients with UC in remission. MATERIALS AND METHODS: Prospective, multicenter study that included UC patients in clinical remission for ≥6 months on maintenance treatment with mesalamine. Patients were evaluated clinically and semi-quantitative FC was measured using a monoclonal immunochromatography rapid test at baseline and every three months until relapse or 12 months of follow-up. RESULTS: One hundred and ninety-one patients had at least one determination of FC. At the end of follow-up, 33 patients (17%) experienced clinical relapse. Endoscopic activity at baseline (p = .043) and having had at least one FC > 60 µg/g during the study period (p = .03) were associated with a higher risk of relapse during follow-up. We obtained a total of 636 semi-quantitative FC determinations matched with a three-month follow-up clinical assessment. Having undetectable FC was inversely associated with early relapse (within three months), with a negative predictive value of 98.6% and a sensitivity of 93.9%. CONCLUSIONS: Serial, rapid semi-quantitative measurement of FC may be a useful, easy and cheap monitoring tool for patients with UC in remission.

Reviewing the therapeutic role of budesonide in Crohn's disease. / Revisando el papel terapéutico de la budesonida en la enfermedad de Crohn.

Oral budesonide is a glucocorticoid of primarily local action. In the field of digestive diseases, it is used mainly in inflammatory bowel disease, but also in other indications. This review addresses the pharmacology, pharmacodynamics and therapeutic use of budesonide. Its approved indications are reviewed, as well as other clinical scenarios in which it could play a role, in order to facilitate its use and improve the accuracy of its prescription.

Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the use of thiopurines in inflammatory bowel disease. / Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el uso de tiopurinas en la enfermedad inflamatoria intestinal.

Thiopurines (azathioprine and mercaptopurine) are widely used in patients with inflammatory bowel disease. In this paper, we review the main indications for their use, as well as practical aspects on efficacy, safety and method of administration. They are mainly used to maintain remission in steroid-dependent disease or with ciclosporin to control a severe ulcerative colitis flare-up, as well as to prevent postoperative Crohn's disease recurrence, and also in combination therapy with biologics. About 30-40% of patients will not respond to treatment and 10-20% will not tolerate it due to adverse effects. Before they are prescribed, immunisation status against certain infections should be checked. Determination of thiopurine methyltransferase activity (TPMT) is not mandatory but it increases initial safety. The appropriate dose is 2.5mg/kg/day for azathioprine and 1.5mg/kg/day for mercaptopurine. Some adverse effects are idiosyncratic (digestive intolerance, pancreatitis, fever, arthromyalgia, rash and some forms of hepatotoxicity). Others are dose-dependent (myelotoxicity and other types of hepatotoxicity), and their surveillance should never be interrupted during treatment. If therapy fails or adverse effects develop, management can include switching from one thiopurine to the other, reducing the dose, combining low doses of azathioprine with allopurinol and assessing metabolites, before their use is ruled out. Non-melanoma skin cancer, lymphomas and urinary tract tumours have been linked to thiopurine therapy. Thiopurine use is safe during conception, pregnancy and breastfeeding.