Development of a Prediction Model for Short-Term Remission of Patients with Crohn's Disease Treated with Anti-TNF Drugs.

Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn's disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF drugs in patients with CD. A consecutive cohort of 113 anti-TNF naive patients with CD was stratified according to clinical response as short-term remission (STR) or non-STR (NSTR) at 12 weeks of treatment. We compared the protein expression profiles of plasma samples in a subset of patients from both groups prior to anti-TNF therapy by SWATH proteomics. We identified 18 differentially expressed proteins (p ≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins (p < 0.001), whose differential expression was confirmed by ELISA (p = 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR.

Real-world outcomes of switching from adalimumab originator to adalimumab biosimilar in patients with inflammatory bowel disease: The ADA-SWITCH study.

BACKGROUND AND AIMS: Data on the outcomes after switching from adalimumab (ADA) originator to ADA biosimilar are limited. The aim was to compare the treatment persistence, clinical efficacy, and safety outcomes in inflammatory bowel disease patients who maintained ADA originator vs. those who switched to ADA biosimilar. METHODS: Patients receiving ADA originator who were in clinical remission at standard dose of ADA originator were included. Patients who maintained ADA originator formed the non-switch cohort (NSC), and those who switched to different ADA biosimilars constituted the switch cohort (SC). Clinical remission was defined as a Harvey-Bradshaw index ≤4 in Crohn's disease and a partial Mayo score ≤2 in ulcerative colitis. To control possible confounding effects on treatment discontinuation, an inverse probability treatment weighted proportional hazard Cox regression was performed. RESULTS: Five hundred and twenty-four patients were included: 211 in the SC and 313 in the NSC. The median follow-up was 13 months in the SC and 24 months in the NSC (p < 0.001). The incidence rate of ADA discontinuation was 8% and 7% per patient-year in the SC and in the NSC, respectively (p > 0.05). In the multivariate analysis, switching from ADA originator to ADA biosimilar was not associated with therapy discontinuation. The incidence rate of relapse was 8% per patient-year in the SC and 6% per patient-year in the NSC (p > 0.05). Six percent of the patients had adverse events in the SC vs. 5% in the NSC (p > 0.05). CONCLUSION: Switching to ADA biosimilar did not impair patients' outcomes in comparison with maintaining on the originator.

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn's Disease Patients on Ustekinumab.

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission.

Mesalazine induced interstitial pneumonitis in the COVID era.

Mesalazine is the most widely used aminosalicylate for induction and maintenance of remission in patients with mild-to-moderate ulcerative colitis (UC). Drug-induced hypersensitivity pneumonitis is considered very rare (<1/10.000 patients). Due to its rarity and the scarce cases reported, mesalazine-induced lung injury needs to be highly suspected in a patient with onset of respiratory symptoms and UC under treatment with salicylates. It should make the clinician formulate a differential diagnosis that includes not only infections (tuberculosis, bacterial...) or the inflammatory bowel disease itself, but also the current coronavirus disease 2019 (COVID-19) since their clinical and radiological manifestations may be very similar.

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study.

BACKGROUND: Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn's disease (CD) patients in real-world clinical practice. METHODS: A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. RESULTS: A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). CONCLUSIONS: Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.

This large retrospective study demonstrated the short- and long-term effectiveness and safety of ustekinumab in patients with Crohn's disease in real-world clinical practice, including those with refractory disease.

Risk of Immunomediated Adverse Events and Loss of Response to Infliximab in Elderly Patients with Inflammatory Bowel Disease: A Cohort Study of the ENEIDA Registry.

BACKGROUND AND AIMS: Immunomediated adverse events [IAEs] are the most frequently reported infliximab [IFX]-related adverse events. Combination therapy may reduce their incidence, although this strategy is not recommended in elderly patients. We aimed to compare the rates of IFX-related IAEs and loss of response [LOR] in elderly and younger patients. METHODS: Adult patients in the ENEIDA registry who had received a first course of IFX therapy were identified and grouped into two cohorts regarding age at the beginning of treatment [over 60 years and between 18 and 50 years]. The rates of IAEs and LOR were compared. RESULTS: In total, 939 patients [12%] who started IFX over 60 years of age and 6844 [88%] below 50 years of age were included. Elderly patients presented a higher proportion of AEs related to IFX [23.2% vs 19%; p = 0.002], infections [7.1% vs 4.3%; p < 0.001] and neoplasms [2.2% vs 0.5%; p < 0.001]. In contrast, the rates of IAEs [14.8% vs 14.8%; p = 0.999], infusion reactions [8.1% vs 8.1%; p = 0.989], late hypersensitivity [1.3% vs 1.2%; p = 0.895], paradoxical psoriasis [1% vs 1.5%; p = 0.187] and drug-induced lupus erythematosus [0.6% vs 0.7%; p = 0.947] were similar in elderly and younger patients. LOR rates were also similar between the two groups [20.5% vs 19.3%; p = 0.438]. In the logistic regression analysis, IFX monotherapy, extraintestinal manifestations and female gender were the only risk factors for IAEs, whereas IFX monotherapy, extraintestinal manifestations and Crohn's disease were risk factors for LOR. CONCLUSIONS: Elderly patients with inflammatory bowel disease have a similar risk of developing IFX-related IAEs and LOR to that of younger patients.

Fendrix vs Engerix-B for Primo-Vaccination Against Hepatitis B Infection in Patients With Inflammatory Bowel Disease: A Randomized Clinical Trial.

INTRODUCTION: To compare Engerix-B and Fendrix hepatitis B virus for primo vaccination in inflammatory bowel disease (IBD). METHODS: Patients with IBD were randomized 1:1 to receive Engerix-B double dose or Fendrix single dose at months 0, 1, 2, and 6. Anti-HBs titers were measured 2 months after the third and fourth doses. Response to vaccination was defined as anti-HBs ≥100 UI/L. Anti-HBs titers were measured 2 months after the third and fourth doses and again at 6 and 12 months after the fourth dose. RESULTS: A total of 173 patients were randomized (54% received Engerix-B and 46% Fendrix). Overall, 45% of patients responded (anti-HBs ≥100 IU/L) after 3 doses and 71% after the fourth dose. The response rate after the fourth dose was 75% with Fendrix vs 68% with Engerix-B (P = 0.3). Older age and treatment with steroids, immunomodulators, or anti-tumor necrosis factor were associated with a lower probability of response. However, the type of vaccine was not associated with the response. Anti-HBs titer negativization occurred in 13% of patients after 6 months and 20% after 12 months. Anti-HBs ≥100 IU/L after vaccination was the only factor associated with maintaining anti-HBs titers during follow-up. DISCUSSION: We could not demonstrate a higher response rate of Fendrix (single dose) over Engerix-B (double dose). A 4-dose schedule is more effective than a 3-dose regimen. Older age and treatment with immunomodulators or anti-tumor necrosis factors impaired the success. A high proportion of IBD patients with protective anti-HBs titers after vaccination loose them over time. The risk of losing protective anti-HBs titers is increased in patients achieving anti-HBs <100 IU/L after the vaccination.

Antitumor Necrosis Factor Agents to Treat Endoscopic Postoperative Recurrence of Crohn's Disease: A Nationwide Study With Propensity-Matched Score Analysis.

INTRODUCTION: Patients with Crohn's disease experiencing endoscopic postoperative recurrence (POR) may benefit from antitumor necrosis factor (TNF) agents but scarce data on this are available. Our aim was to assess the efficacy of anti-TNF in improving mucosal lesions in patients with endoscopic POR. METHODS: Multicenter, retrospective, study of patients with Crohn's disease who underwent therapy with anti-TNF agents for endoscopic POR (Rutgeerts score > i1). Treatment outcomes were assessed by the findings in the last ileocolonoscopy performed after anti-TNF therapy was initiated. Endoscopic improvement and remission were defined as any reduction in the baseline Rutgeerts score and by a Rutgeerts score < i2, respectively. RESULTS: A total of 179 patients were included, 83 were treated with infliximab and 96 with adalimumab. Median time on anti-TNF therapy at the last endoscopic assessment was 31 months (interquartile range, 13-54). Endoscopic improvement was observed in 61%, including 42% who achieved endoscopic remission. Concomitant use of thiopurines and treatment with infliximab were associated with endoscopic improvement (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.04-4.46; P = 0.03, and OR 2.34, 95% CI 1.18-4.62; P < 0.01, respectively) and endoscopic remission (OR 3.16, 95% CI 1.65-6.05; P < 0.01, and OR 2.01, 95% CI 1.05-3.88; P = 0.04, respectively) in the multivariable logistic regression analysis. These results were confirmed in a propensity-matched score analysis. DISCUSSION: In patients with endoscopic POR, anti-TNF agents improve mucosal lesions in almost two-thirds of the patients. In this setting, concomitant use of thiopurines and use of infliximab seem to be more effective in improving mucosal lesions.

Real-world long-term effectiveness of ustekinumab in Crohn's disease: results from the ENEIDA registry.

BACKGROUND: Data on the long-term administration of ustekinumab in recommended doses are limited. AIM: To assess the real-world, long-term effectiveness of ustekinumab in refractory Crohn's disease (CD). METHODS: Multi-centre study of CD patients starting ustekinumab at the recommended dose, followed for 1 year. Values for the Harvey-Bradshaw Index (HBI), endoscopic activity, C-reactive protein (CRP), and faecal calprotectin (FC) were recorded at baseline and at weeks 26 and 52. Demographic and clinical data, previous treatments, adverse events (AEs) and hospitalisations were documented. Potential predictors of remission were examined. RESULTS: A total of 407 patients were analysed. The initial maintenance dose of 90 mg SC was administered every 12, 8 and 4 weeks in 56 (14%), 347 (85%) and 4 (1%) patients, respectively. After 52 weeks, treatment was discontinued in 112 patients (27.5%). At baseline, 295 (72%) had an HBI >4 points. Of these, 169 (57%) and 190 (64%) achieved clinical remission at weeks 26 and 52, respectively. FC levels returned to normal in 44% and 54% of patients at weeks 26 and 52, and CRP returned to normal in 36% and 37% of patients at weeks 26 and 52, respectively. AEs were recorded in 60 patients. The use of fewer previous anti-TNFα agents and ileal localisation were associated with clinical remission, and endoscopic severity was associated with poor response. No factors correlated with endoscopic remission. CONCLUSION: After 52 weeks, ustekinumab demonstrated effectiveness in inducing clinical and endoscopic remission in patients with refractory CD.

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.

Adalimumab or Infliximab for the Prevention of Early Postoperative Recurrence of Crohn Disease: Results From the ENEIDA Registry.

BACKGROUND: Anti-tumor necrosis factor agents (anti-TNFs) are efficacious at preventing the postoperative recurrence (POR) of Crohn disease, as demonstrated in 2 randomized controlled trials. However, real-life data for infliximab or adalimumab in this setting are scarce. Our aim was to assess both the efficiency of anti-TNFs at preventing early POR of Crohn disease in clinical practice and the associated risk factors for POR. METHODS: Patients in whom anti-TNFs were prescribed for the prevention of POR within 3 months after ileocolonic resection and who had an endoscopic assessment within 18 months were identified from the ENEIDA registry. Clinical and endoscopic features were collected within 18 months after surgery. RESULTS: In total, 152 patients were included (55 treated with infliximab, 97 with adalimumab, and 39% with concomitant immunosuppressants). Anti-TNF treatment was started after a median time of 29 days (IQR 13-44) after surgery. Eighty-two percent of patients had at least one risk factor for POR, and 82% had been exposed to anti-TNFs before the index surgery. Overall, 34% had endoscopic POR (as defined using a Rutgeerts endoscopic score > i1); 14% had advanced endoscopic POR (>i2); and 20% had clinical POR, with no differences between infliximab and adalimumab. In the multivariate analysis, only perianal disease (odds ratio 2.73, 95% confidence interval [CI] 1.26-5.91) and rectal involvement (odds ratio 2.79, 95% CI 1.09-7.14) were independent predictors of endoscopic POR. CONCLUSIONS: In clinical practice, anti-TNFs for the prevention of POR of Crohn disease are frequently used in patients experienced with anti-TNFs and with concomitant immunosuppressants. The efficacy of infliximab and adalimumab for POR prevention is similar and in accordance with the results obtained in randomized controlled trials.

Differences between childhood- and adulthood-onset inflammatory bowel disease: the CAROUSEL study from GETECCU.

BACKGROUND: Cohort studies comparing the characteristics of childhood-onset and adulthood-onset inflammatory bowel disease (IBD) in the biologics era are scarce. AIM: To compare disease characteristics, the use of immunomodulators and biologic agents and the need for surgery between childhood- and adulthood-onset IBD. METHODS: Inflammatory bowel disease patients from the ENEIDA registry diagnosed between 2007 and 2017 were included. The childhood-onset cohort comprised patients diagnosed at ≤16 years of age and the adulthood-onset cohort those diagnosed at >16 years. The cumulative incidences of immunosuppressive therapy, biologic therapy and surgery were estimated using Kaplan-Meier curves, compared by the log-rank test. Cox regression analysis was performed to identify potential predictive factors of treatment with immunosuppressants, biologic agents or surgery. RESULTS: The adulthood-onset cohort comprised 21 200 patients out of 20 354 (96%) and the childhood-onset cohort 846 (4%). Median follow-up was 54 months in the childhood-onset cohort and 38 months in the adulthood-onset cohort (P < 0.01). Proportions of Crohn's disease, ileocolonic involvement and inflammatory behaviour at diagnosis were higher in the childhood-onset cohort. In the multivariate analysis, after adjusting for sex, type of IBD, extraintestinal manifestations, family history and smoking habit, childhood-onset IBD was associated with higher risk of immunomodulator use (hazard ratio [HR] = 1.2, 95% confidence interval [95% CI] = 1.1-1.2) and higher probability of receiving biologic treatment (HR = 1.2, 95% CI = 1.1-1.3). However, childhood-onset IBD was not associated with higher risk of surgery (HR = 0.9, 95% CI = 0.8-1.2). CONCLUSIONS: Childhood-onset IBD has differential characteristics and higher risk of treatment with immunomodulators and biologic agents, compared with adulthood-onset IBD. Nevertheless, paediatric IBD is not associated with higher risk of surgery.

Characteristics of inflammatory bowel disease in patients of Roma/Gypsy ethnicity. A case-control study.

BACKGROUND: Peculiarities of inflammatory bowel disease (IBD) have been explored in ethnic groups, such as Asians, Hispanics, and Afro-Americans, but not in other ethnic minorities, such as Roma/Gypsies. METHODS: In a retrospective, hospital-based study, all adult Roma/Gypsy patients included in the IBD databases of seven Spanish centres were identified as cases. For each Roma/Gypsy patient, a Caucasian patient, matched for several demographic features, was searched as a control. Data on phenotypic features, therapeutic requirements, and familial aggregation were recorded. RESULTS: Sixty-eight Roma/Gypsy patients were identified, 29 of them being women. The mean age at diagnosis of IBD was 24.9±9.5years, and the mean time elapsed since diagnosis was 96.6±72.2months. Roma/Gypsy IBD patients showed a significantly higher rate of familial aggregation (43%) than their Caucasian controls (9%) (p=0.00001). CD in Roma/Gypsies had more often a complicated pattern (mainly penetrating) while UC patients showed a marked trend to more often developing extraintestinal manifestations. In addition, Roma/Gypsy IBD patients had a somewhat greater need for immunosuppressants, biological agents or surgery. CONCLUSIONS: These are the first data on IBD in Roma/Gypsy patients. Familial aggregation is the most prominent feature in these patients, suggesting a predominant role of genetics in its pathogenesis.

Bile acid malabsorption in patients with chronic diarrhea and Crohn's disease.

INTRODUCTION AND AIM: Crohn's disease (CD) is a form of inflammatory bowel disease and is mainly characterized by diarrhea and abdominal pain. The aim of our study was to analyze the usefulness of performing a 75SeHCAT scan in CD patients with chronic diarrhea and suspected bile acid malabsorption (BAM). In addition, we aimed to determine whether there was a relationship with the clinical features of the disease and a previous bowel resection. PATIENTS AND METHODS: this was an observational cross-sectional study of 39 patients with a diagnosis of CD and chronic diarrhea. All cases underwent a 75SeHCAT scan for BAM diagnosis, after discarding disease activity. RESULTS: the study cohort included 19 females and 20 males. The median age was 44 years and the majority of patients were A2 L1 B1 according to the Montreal classification; 84.6% of patients had undergone a previous bowel resection. BAM was present in 97.4% of patients (100% and 83.3% of patients with and without previous surgery, respectively), which was severe in 92.1% of cases. Treatment with bile acid sequestrants was initiated and a favorable response was obtained in 72.2% of patients. The relationship between BAM degree (moderate or severe), bowel surgery and the response to bile acid sequestrant treatment was also analyzed but not statistically significant. CONCLUSION: BAM is a frequent cause of diarrhea in CD patients in endoscopic or radiological remission. This condition was present in all patients with a history of a bowel resection. A response to bile acid sequestrants treatment was observed in 73% of patients.

[Non-oropharyngeal dysphagia with frequent Emergency Room attendance]. / Disfagia no orofaríngea con alta frecuentación en Urgencias.

BACKGROUND: avoidant/restrictive food intake disorder (ARFID) is a new eating disorder category among eating disorders. Its recent incorporation explains the lack of studies evaluating the optimal treatment and follow-up of patients with this disorder. CASE REPORT: we present the case of a 20-year-old patient with 3-week dysphagia and 20% weight loss. After ruling out organic disorders, he was diagnosed with ARFID and required parenteral and tube feeding until the improvement of the eating disorder. DISCUSSION: in this patient, severe caloric malnutrition secondary to the eating disorder made it necessary to turn to the parenteral and enteral approach until the behavioral modification and progressive food exposure were effective. The absence of etiological treatment makes cognitive behavioral intervention, along with the correction of nutritional deficiencies, the preferred approach.

Introducción: el trastorno de evitación/restricción de la ingesta alimentaria es una nueva categoría diagnóstica en el espectro de trastornos de la alimentación. Su reciente aparición explica la falta de estudios que evalúen el tratamiento y seguimiento de pacientes con esta patología.Caso clínico: presentamos el caso de un paciente de 20 años con disfagia de tres semanas de evolución y pérdida del 20% de peso, diagnosticado de trastorno de evitación/restricción de la ingesta alimentaria tras descartar organicidad del proceso, con necesidad de nutrición parenteral y enteral como tratamiento nutricional hasta mejoría clínica.Discusión: en este paciente, la desnutrición calórica grave secundaria al trastorno alimentario hizo necesario recurrir al aporte parenteral y enteral hasta la modificación conductual y la reintroducción paulatina de la alimentación por vía oral. La ausencia de tratamiento etiológico hace que la terapia conductual junto con la corrección de los déficits nutricionales sean la base del manejo.

Prevalence of iron deficiency without anaemia in inflammatory bowel disease and impact on health-related quality of life. / Prevalencia de déficit de hierro sin anemia en la enfermedad inflamatoria intestinal y su impacto en la calidad de vida.

INTRODUCTION: Iron deficiency without anaemia (IDWA) is commonly found in outpatients with inflammatory bowel disease (IBD) in an even higher proportion than anaemia. However, its true prevalence and possible impact on health-related quality of life (HRQoL) are unknown. The objectives of this study were: to establish the prevalence of IDWA, identify possible associated factors and measure their impact on HRQoL. MATERIAL AND METHODS: 127 patients with IBD in an outpatient setting were consecutively included in an observational, descriptive, cross-sectional study. IDWA was defined as ferritin levels of <100 ng/ml with inflammatory activity or ≤30 ng/ml without it, with transferrin saturation of ≤16%, and with normal haemoglobin levels. HRQoL was assessed using two questionnaires: the IBDQ-9 for symptoms related to IBD and the FACIT-F to measure the presence of fatigue. Fatigue was considered extreme with a score of ≤30 points. RESULTS: The prevalence of IDWA was 37%. Variables associated with its occurrence were female gender (OR=2.9; p=.015) and the presence of inflammatory activity (OR=9.4; p=.001). Patients with IDWA presented HRQoL questionnaires with lower overall scores; decreases of 6.6 (p<.001) and 4.3 (p=.037) points in the IBDQ-9 and the FACIT-F were recorded, respectively. In addition, an increase of 29.4% in the presence of extreme fatigue was observed. CONCLUSION: The prevalence of IDWA is considerable in outpatients with IBD. IDWA is associated with female gender and inflammatory activity. It has a clear negative impact on HRQoL. A more active approach is needed to treat this complication.

Evolution after switching to biosimilar infliximab in inflammatory bowel disease patients in clinical remission. / Evolución tras el intercambio a infliximab biosimilar en pacientes con enfermedad inflamatoria intestinal en remisión clínica.

BACKGROUND AND AIM: The biosimilar of infliximab (CT-P13) has been approved for the same indications held by the infliximab reference product (Remicade®); however, there are few clinical data on switching in inflammatory bowel disease (IBD). The aim of this study was to assess the efficacy, safety, bioavailability profile and factors associated with relapse after switching to biosimilar infliximab in IBD patients in clinical remission. MATERIAL AND METHOD: Observational study with IBD patients treated with Remicade® for at least 6 months and in clinical remission for at least 3 months who switched to infliximab biosimilar. The incidence of relapse, adverse effects and possible changes in drug bioavailability (trough level and antidrug antibodies) were evaluated. RESULTS: Thirty six patients were included (63.9% CD) with a mean follow-up of 8.4 months (SD±3.5). The 13.9% had clinical relapse. The longer clinical remission time before switching (HR=0.54, 95% CI=0.29-0.98, P=.04) and detectable infliximab levels at the time of switching (HR=0.03, 95% CI=0.001-0.89, P=.04) were associated with a lower risk of relapse. No differences were found between infliximab levels at the time of switching and at weeks 8 and 16 (P=.94); 8.3% of the patients had some adverse event, requiring the suspension of biosimilar in one patient for severe pneumonia. CONCLUSION: Switching to biosimilar infliximab in a real-life cohort of IBD patients in clinical remission did not have a significant impact on short-term clinical outcomes. The factors associated with relapse were similar to those expected in patients continuing with Remicade®.

Adherence to a predefined vaccination program in patients with inflammatory bowel disease.

INTRODUCTION: The application of vaccination programs in patients with inflammatory bowel disease (IBD) is heterogeneous and generally deficient. As a result, adherence in these patients to a predefined vaccination program has not been clearly established. The aim of this study was to estimate adherence to a predefined vaccination program among patients with IBD and to identify the factors that may predict poor adherence. METHODS: All patients diagnosed with IBD and followed-up between January and March 2012 were referred to the Department of Preventive Medicine for evaluation of their immune status (with serological testing for hepatitis A, B and C viruses, varicella-zoster virus, mumps, rubella and measles), followed by vaccination based on the test results obtained and on the patient's vaccination history. The percentage of adherence to the vaccination program was determined, along with the factors associated with low adherence. RESULTS: A total of 153 patients with IBD (ulcerative colitis in 50.3% and Crohn's disease in 49.7%) were included (45.1% men and 54.9% women; mean age 43.30±14.19 years, range 17-83). The vaccination program adherence rate was 84.3%. The factors associated with poor adherence were drugs related to IBD (patients not receiving immunosuppressants and/or biological agents showed lower adherence than those receiving these treatments; p=0.021), adherence to medical treatment (poor adherence to treatment was also associated with poor adherence to vaccination; p=0.016), and marital status (single, divorced or separated patients showed lower adherence than married individuals; p=0.015). CONCLUSION: Adherence to vaccination is acceptable among patients with IBD. However, specific actions, such as optimization of patient information on the disease and emphasis on the need for adequate vaccination, are to improve adherence.

Prognosis of Patients with Ulcerative Colitis in Sustained Remission After Thiopurines Withdrawal.

BACKGROUND: The ideal length of treatment with thiopurines in patients with ulcerative colitis (UC) in sustained remission remains unknown. It is widely accepted that the drug withdrawal is associated with a worse outcome. The aim of this study was to analyze the outcome after this withdrawal and to identify predictors of relapse. METHODS: A multicenter and retrospective study was designed. A total of 102 patients with UC who discontinued thiopurines in a situation of sustained remission were included. All the patients were followed up until last revision or until relapse (understood as the occurrence of signs and symptoms of UC that required a rescue treatment). RESULTS: After thiopurines withdrawal, overall relapse was recorded in 32.35% of the patients: 18.88% in the first year, 36.48% in the third, and 43.04% in the fifth year after withdrawal. On multivariate analysis, predictors of relapse were the time from diagnosis of UC until the starting of thiopurines (hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.01-1.02; P = 0.039), the number of relapses before the withdrawal (HR, 1.3; 95% CI, 1.01-1.66; P = 0.029), pancolitis (HR, 5.01; 95% CI, 1.95-26.43; P = 0.028), the duration of treatment with thiopurines (HR, 0.15; 95% CI, 0.03-0.66; P = 0.013) and the situation of biological remission at withdrawal (HR, 0.004; 95% CI, 0.0001-0.14; P = 0.002). CONCLUSIONS: The withdrawal of thiopurines in patients with UC, although in sustained remission, is related to a high relapse rate. Clinical variables such as the extent of the disease, the duration of treatment or time from diagnosis to the start of thiopurines should be considered before stopping these drugs.

Resources Utilization and Costs the Year Before and After Starting Treatment with Adalimumab in Crohn's Disease Patients.

BACKGROUND: This study examines the resources utilization in patients with Crohn's disease (CD) during the year before (Y - 1) and after (Y + 1) starting treatment with adalimumab and the drug's efficiency. METHODS: Observational, multicenter, prospective cohort study of patients with CD naive to biological drugs. The proportion of patients with CD Activity Index (CDAI) <150 was considered as the effectiveness variable. Costs considered were direct costs (DC) related to the use of health care resources, and indirect costs (IC) related to sick leave in Y - 1 and Y + 1. Adalimumab efficiency was estimated as the incremental cost/effectiveness ratio. A deterministic sensitivity analysis was performed building 3 scenarios: base case, the least favorable, and the most favorable case for adalimumab. RESULTS: In the cohort of 126 patients (50.8% men; age 39.1 ± 13.8 yr), the proportion of patients in remission increased from 34.1% by the end of Y - 1 to 83.3% by the end of Y + 1. Although the DC increase by the use of adalimumab, the use of doctor visits, emergency room visits, laboratory tests, diagnostic examinations, and nonbiological drug treatment were lower (P < 0.05) in Y + 1 than Y - 1. In the base case scenario, considering only DC, the incremental cost/effectiveness ratio was €31,308 and including IC, it was €28,936. In patients with CDAI > 150 at the onset, incremental cost/effectiveness ratio was €20,119 and €18,223, considering DC alone or included IC, respectively. CONCLUSIONS: In patients with CD, adalimumab increases pharmacological costs at the expense of biological therapy but reduces the cost of other drugs, the use of health care resources, and IC. Adalimumab efficiency is 30% greater in patients with CDAI > 150.