Immunomodulatory Therapy Does Not Increase the Risk of Cancer in Persons With Inflammatory Bowel Disease and a History of Extracolonic Cancers.

OBJECTIVES: Immunosuppressant therapies (IMTs; thiopurines, anti-tumor necrosis factor agents) may influence the immunologic control of cancer and might facilitate the spread and recurrence of cancer. This study assesses the impact of the use of IMTs on the development of incident cancers (recurrent or new) in patients with inflammatory bowel disease (IBD) and a history of malignancy. METHODS: Patients with IBD included in the ENEIDA registry with a history of cancer without being exposed to IMTs were identified and retrospectively reviewed and compared regarding further treatment with IMTs or not by means of a log-rank test. RESULTS: Overall, 520 patients with previous extracolonic cancer naive to IMTs before the diagnosis of cancer were identified. Of these, 146 were subsequently treated with IMTs (exposed), whereas 374 were not (nonexposed). The proportion of patients with incident cancers was similar in both exposed (16%) and nonexposed (18%) patients (P = 0.53); however, there was more than a 10-year difference in the age at index cancer between these 2 groups. Cancer-free survival was 99%, 98%, and 97% at 1, 2, and 5 years in exposed patients, and 97%, 96%, and 92% at 1, 2, and 5 years in non-exposed patients, respectively (P = 0.03). No differences in incident cancer rates were observed between exposed and nonexposed patients when including only those who were exposed within the first 5 years after cancer diagnosis. DISCUSSION: In patients with IBD and a history of cancer not related to immunosuppression, the use of IMTs is not associated with an increased risk of new or recurrent cancers even when IMTs are started early after cancer diagnosis.

[European registry Helicobacter pylori (Hp-EuReg): how has clinical practice changed in Russia from 2013 to 2018 years].

The multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group (EHMSG) is conducted in 27 countries in Europe. The data from the Russian part of the European registry for the management of Helicobacter pylori infection (European Registry on the management of Helicobacter pylori infection, protocol: "Hp-EuReg") allows us to analyze the real clinical practice of diagnosis and treatment of H. pylori and compare it with international recommendations. MATERIALS AND METHODS: A comparative analysis of the data entered in the register by the Russian research centers "Hp-EuReg", in the period from 2013 to 2018, was conducted. RESULTS AND DISCUSSION: Invasive diagnostic methods prevail for the primary diagnosis of H. pylori [histology - 20.3% (in 2013 year) - 43.9% (in 2018 year), rapid urease test - 31.7% and 47.8% respectively]. The most popular mode of eradication therapy is a 10-day triple therapy (62.8-76.2%), the effectiveness of which does not exceed 79% (per protocol). Invasive tests (histology) are the leading method for control the effectiveness of therapy, however, there is a tendency towards a wider use of non-invasive methods (H. pylori stool antigen - from 17% in 2013 to 29.3% in 2018 and urea breath test from 6.9 to 18.3%, respectively). Serological test to control the effectiveness of eradication is still used from 8.2% (2013) to 6.1% (2018). Eradication therapy was not performed in 28% of patients throughout the entire observation period. CONCLUSION: In Russia, despite approved domestic and international recommendations, deviations in clinical practice persist, both during eradication therapy and in monitoring the effectiveness of eradication therapy.

Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.

OBJECTIVE: Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN: Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS: After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS: In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER: EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.

Post-operative morbidity and mortality of a cohort of steroid refractory acute severe ulcerative colitis: Nationwide multicenter study of the GETECCU ENEIDA Registry.

BACKGROUND: Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. METHODS: We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. RESULTS: During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age ≥50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). CONCLUSIONS: The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

European Registry on the management of Helicobacter pylori infection (Hp-EuReg): analysis of 2360 patients receiving first-line therapy in Russia.

AIM: European Registry on the management of Helicobacter pylori infection («Hp-EuReg¼) - a multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group, conducted in 27 European countries in order to evaluate the real clinical practice of diagnosis and treatment of H. pylori and its comparison with international recommendations. MATERIALS AND METHODS: The analysis of 2360 patients entered in the register by the Russian centres of «Hp-EuReg¼ in 2013-2017, who were underwent 1st line eradication therapy. RESULTS: The most common methods of primary diagnosis of H. pylori are histological (37.7%), rapid urease test (29.2%) and serology (29.7%). The duration of eradication therapy in 9.4% of cases was 7 days, in 65.3% - 10 days, and in 25.3% - 14 days. To control the effec- tiveness of treatment, H. pylori antigen in feces (31.3%), urea breath test (23.4%) and histological method (23.3%) were used. In 3.6% cases was used serology by mistake. In 17.3% of patients control was not carried out. The effectiveness of triple therapy with a PPI, amoxicillin, clar- ithromycin (per protocol) was 67.6%, with 7-day course, 81.1% at 10-day and 86.7% at 14-day course. Eradication rate of triple therapy with addition of bismuth (per protocol) reached 90,6% in the group receiving 10-day scheme and 93.6% in the group receiving the 14-day treatment. CONCLUSION: Significant deviations of clinical practice from expert recommendations, most pronounced at the stage of monitoring the effectiveness of therapy, were noted. The suboptimal efficacy of triple therapy is shown.

Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report.

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

Extracolonic Cancer in Inflammatory Bowel Disease: Data from the GETECCU Eneida Registry.

OBJECTIVES: The objective of this study was (a) To know the prevalence and distribution of extracolonic cancer (EC) in patients with inflammatory bowel disease (IBD); (b) To estimate the incidence rate of EC; (c) To evaluate the association between EC and treatment with immunosuppressants and anti-tumor necrosis factor (TNF) agents. METHODS: This was an observational cohort study. INCLUSION CRITERIA: IBD and inclusion in the ENEIDA Project (a prospectively maintained registry) from GETECCU. EXCLUSION CRITERIA: Patients with EC before the diagnosis of IBD, lack of relevant data for this study, and previous treatment with immunosuppressants other than corticosteroids, thiopurines, methotrexate, or anti-TNF agents. The Kaplan-Meier method was used to evaluate the impact of several variables on the risk of EC, and any differences between survival curves were evaluated using the log-rank test. Stepwise multivariate Cox regression analysis was used to investigate factors potentially associated with the development of EC, including drugs for the treatment of IBD, during follow-up. RESULTS: A total of 11,011 patients met the inclusion criteria and were followed for a median of 98 months. Forty-eight percent of patients (5,303) had been exposed to immunosuppressants or anti-TNF drugs, 45.8% had been exposed to thiopurines, 4.7% to methotrexate, and 21.6% to anti-TNF drugs. The prevalence of EC was 3.6%. In the multivariate analysis, age (HR=1.05, 95% CI=1.04-1.06) and having smoked (hazards ratio (HR)=1.47, 95% confidence interval (CI)=1.10-1.80) were the only variables associated with a higher risk of EC. CONCLUSIONS: Neither immunosuppressants nor anti-TNF drugs seem to increase the risk of EC. Older age and smoking were associated with a higher prevalence of EC.

Effect of Chondroitin Sulphate on Pro-Inflammatory Mediators and Disease Activity in Patients with Inflammatory Bowel Disease.

BACKGROUND/AIMS: To evaluate the incidence rate of relapse in patients with inflammatory bowel disease (IBD) undergoing chondroitin sulphate (CS) treatment and its effect on the concentrations of several pro-inflammatory proteins. METHODS: Prospective, observational, 12-month follow-up study in patients with IBD in remission, starting CS (Condrosan®, Bioiberica S.A.) treatment for osteoarthritis (OA). Crohn's Disease Activity Index and modified Truelove-Witts severity index were calculated for Crohn's disease and ulcerative colitis (UC) respectively. Levels of vascular endothelial growth factor (VEGFA), -C, fibroblast growth factor 2, hepatocyte growth factor, angiopoietin (Ang)-1, Ang-2, transforming growth factor beta, tumour necrosis factor alpha, interleukin (IL)-1ß, IL-6, IL-12, IL-17, IL-23, intracellular adhesion molecule-1, vascular adhesion molecule-1, matrix metalloproteinase-3 and PGE2 were quantified by ELISA. OA joint pain was evaluated using a visual analogue scale. RESULTS: A total of 37 patients (19 UC and 18 Crohn's disease) were included. The mean values for OA joint pain decreased after 12 months from 5.9 ± 2.8 to 3.0 ± 2.3 (p < 0.05). Only 1 patient (with UC) flared during follow-up. The incidence rate of relapse was 3.4% per patient-year of follow-up. Mean serum VEGFA levels increased between baseline (492 pg/ml) and 12-month treatment (799 pg/ml; p < 0.05). CONCLUSION: The incidence of IBD relapse in patients under CS treatment was lower than that generally reported. This treatment might modulate VEGFA. CS decreases OA-related pain in patients with IBD.

Third-line rescue therapy with bismuth-containing quadruple regimen after failure of two treatments (with clarithromycin and levofloxacin) for H. pylori infection.

BACKGROUND: Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin fails in >20 % of cases. A rescue therapy with PPI-amoxicillin-levofloxacin still fails in >20 % of patients. AIM: To evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen in patients with two consecutive eradication failures. METHODS: Prospective multicenter study of patients in whom 1st treatment with PPI-clarithromycin-amoxicillin and 2nd with PPI-amoxicillin-levofloxacin had failed. A 3rd eradication regimen with a 7- to 14-day PPI (standard dose b.i.d.), bismuth subcitrate (120 mg q.i.d. or 240 mg b.i.d.), tetracycline (from 250 mg t.i.d. to 500 mg q.i.d.) and metronidazole (from 250 mg t.i.d. to 500 mg q.i.d.). Eradication was confirmed by (13)C-urea-breath-test 4-8 weeks after therapy. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by means of a questionnaire. RESULTS: Two hundred patients (mean age 50 years, 55 % females, 20 % peptic ulcer/80 % uninvestigated-functional dyspepsia) were initially included, and two were lost to follow-up. In all, 97 % of patients complied with the protocol. Per-protocol and intention-to-treat eradication rates were 67 % (95 % CI 60-74 %) and 65 % (58-72 %). Adverse effects were reported in 22 % of patients, the most common being nausea (12 %), abdominal pain (11 %), metallic taste (8.5 %), and diarrhea (8 %), none of them severe. CONCLUSION: A bismuth-containing quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with standard clarithromycin- and levofloxacin-containing triple therapies.

Safety of thiopurines and anti-TNF-α drugs during pregnancy in patients with inflammatory bowel disease.

OBJECTIVES: The safety of thiopurines and anti-tumor necrosis factor-α (TNF-α) drugs during pregnancy remains controversial, as the experience with these drugs in this situation is limited. Our aim is to assess the safety of thiopurines and anti-TNF-α drugs for the treatment of inflammatory bowel disease (IBD) during pregnancy. METHODS: Retrospective, multicenter study in IBD patients. Pregnancies were classified according to the therapeutic regimens during pregnancy or during the 3 months before the conception: non-exposed group, pregnancies exposed to thiopurines alone (group A), and pregnancies exposed to anti-TNF-α drugs (group B). An unfavorable Global Pregnancy Outcome (GPO) was considered if pregnancy developed with obstetric complications in the mother and in the newborn. RESULTS: A total of 187 pregnancies in the group A, 66 pregnancies in the group B, and 318 pregnancies in the non-exposed group were included. The rate of unfavorable GPO was different among the three groups (31.8% in non-exposed group, 21.9% in group A, and 34.8% in group B), being lower in pregnancies under thiopurines than among non-exposed (P = 0.01). The rate of pregnancy complications was similar among the three groups (27.7% in non-exposed, 20.9% in group A, and 30.3% in group B). The rate of neonatal complications was different among the three groups (23.3% in non-exposed group, 13.9% in group A, and 21.2% in group B), being lower in pregnancies under thiopurines than among non-exposed (P = 0.01). In the multivariate analysis, the treatment with thiopurines (odds ratio = 0.6; 95% confidence interval = 0.4-0.9, P = 0.02) was the only predictor of favorable GPO, whereas maternal age >35 years at conception was the only predictor of unfavorable GPO. The treatment with anti-TNF-α drugs was not associated with an unfavorable GPO. CONCLUSION: The treatment with thiopurines and anti-TNF-α drugs does not seem to increase the risk of complications during pregnancy and does seem to be safe for the newborn.

Health care costs of complex perianal fistula in Crohn's disease.

AIM: To evaluate the use of health care resources and the associated costs of complex perianal Crohn's disease (CD) from the National Health System perspective. METHODS: We conducted a multicenter, retrospective, observational study in which gastroenterologists from 11 hospitals in the Community of Madrid took part. Data was collected on the direct healthcare resources (pharmacological treatments, surgical procedures, laboratory/diagnostic tests, visits to specialists and emergency departments, and hospitalizations) consumed by 97 adult patients with complex perianal CD which was active at some point between January 1, 2005, and case history review. RESULTS: We recorded 527 treatments: 73.1% pharmacological (32.3% antibiotic, 20.5% immunomodulator, 20.3% biological) and 26.9% surgical. Mean annual global cost was €8,289/patient, 75.3% (€6,242) of which was accounted for by pharmacological treatments (€13.44 antibiotics; €1,136 immunomodulators; €5,093 biological agents), 12.4% (€1,027) by hospitalizations and surgery, 7.7% (€640) by medical visits, 4.2% (€350) by laboratory/diagnostic tests, and 0.4% (€30) by emergency department visits. CONCLUSIONS: Pharmacological therapies, and in particular biological agents, are the main cost driver in complex perianal CD; costs due to surgery and hospitalizations are much lower.

Efficacy of hepatitis B vaccination and revaccination and factors impacting on response in patients with inflammatory bowel disease.

OBJECTIVES: We assessed the effectiveness of hepatitis B virus (HBV) vaccine in inflammatory bowel disease (IBD) patients, evaluated the impact of immunosuppressors and anti-tumor necrosis factor (anti-TNF) agents, and assessed the effectiveness of revaccination. METHODS: IBD patients were vaccinated against HBV with a quick (0, 1, and 2 months) and double-dose schedule (Engerix B). A second vaccination was administered to nonresponders. RESULTS: Of 241 vaccinated patients, anti-HBs was >10 IU/l in 59% and >100 IU/l in 39%. The response rate (anti-HBs >10 IU/l) was lower among patients under anti-TNF therapy: 46% vs. 62%. In the multivariate analysis, a lower response rate was demonstrated in older patients and those receiving anti-TNFs. The response rate (anti-HBs >100 IU/l) after revaccination was 42%. CONCLUSIONS: The response rate to the HBV vaccination--even with a double-dose schedule--is very low in IBD patients, mainly in those receiving anti-TNFs. However, treatment with immunosuppressors did not affect the efficacy of the vaccine. A considerable--albeit insufficient--success rate may be obtained when two consecutive vaccination courses, each with a three-dose vaccine series, are administered.

Long-term follow-up of 1,000 patients cured of Helicobacter pylori infection following an episode of peptic ulcer bleeding.

OBJECTIVES: To evaluate the effect of Helicobacter pylori (H. pylori) eradication on ulcer bleeding recurrence in a prospective, long-term study including 1,000 patients. METHODS: Patients with peptic ulcer bleeding were prospectively included. Prior non-steroidal anti-inflammatory drug (NSAID) use was not considered exclusion criteria. H. pylori infection was confirmed by rapid urease test, histology, or (13)C-urea breath test. Several eradication therapies were used. Subsequently, ranitidine 150 mg o.d. was administered until eradication was confirmed by (13)C-urea breath test 8 weeks after completing therapy. Patients with therapy failure received a second, third, or fourth course of eradication therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy and were controlled yearly with a repeat breath test. NSAID use was not permitted during follow-up. RESULTS: Thousand patients were followed up for at least 12 months, with a total of 3,253 patient-years of follow-up. Mean age 56 years, 75% males, 41% previous NSAID users. In all, 69% had duodenal ulcer, 27% gastric ulcer, and 4% pyloric ulcer. Recurrence of bleeding was demonstrated in three patients at 1 year (which occurred after NSAID use in two cases, and after H. pylori reinfection in another one), and in two more patients at 2 years (one after NSAID use and another after H. pylori reinfection). The cumulative incidence of rebleeding was 0.5% (95% confidence interval, 0.16-1.16%), and the incidence rate of rebleeding was 0.15% (0.05-0.36%) per patient-year of follow up. CONCLUSION: Peptic ulcer rebleeding virtually does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved. However, NSAID intake or H. pylori reinfection may exceptionally cause rebleeding in H. pylori-eradicated patients.

Evaluation of liver fibrosis by transient elastography (Fibroscan®) in patients with inflammatory bowel disease treated with methotrexate: a multicentric trial.

BACKGROUND: Methotrexate is an effective treatment for inflammatory bowel disease (IBD). However, long-term treatments have been associated with the development of liver fibrosis. FibroScan® is a noninvasive, safe, and effective technique to evaluate liver fibrosis. AIM: To evaluate the presence of significant liver fibrosis by transient elastography (FibroScan®) in IBD patients treated with methotrexate. METHODS: Cross-sectional study including IBD patients treated with methotrexate from different hospitals. Clinical and analytical data, duration of treatment, and cumulative dose of methotrexate were obtained. Liver stiffness was assessed by FibroScan®. The cutoff value for significant liver fibrosis (according to METAVIR) was F ≥ 2: 7.1 kPa. Results. In the study, 46 patients were included, 30 women (65%), with a mean age of 43 ± 10 years. 31 patients had Crohn's disease (67.4%), 13 ulcerative colitis (28.3%), and 2 indeterminate colitis (4.3%). The mean cumulative dose of methotrexate was 1242 ± 1349 mg, with a mean treatment duration of 21 ± 24 months. The mean value of liver stiffness was 4.7 ± 6.9 kPa. There were 35 patients (76.1%) with F01, 8 patients (17.4%) with F = 2, and 3 patients with F ≥ 3 (6.5%). There were no differences in liver stiffness depending on sex, age, type of IBD, or cumulative dose of methotrexate. CONCLUSIONS: (1) Development of advanced liver fibrosis in IBD patients treated with methotrexate is exceptional. (2) There were no differences in liver stiffness depending on the type of IBD or the cumulative dose of methotrexate. (3) FibroScan® may be potentially useful for evaluation and follow-up of liver fibrosis in methotrexate-treated patients.

[Nodular regenerative hyperplasia: azathioprine-induced hepatotoxicity in a patient with Crohn's disease]. / Hiperplasia nodular regenerativa: hepatotoxicidad por azatioprina en un paciente con enfermedad de Crohn.

We report the case of a 53-year-old man with Crohn's disease who developed azathioprine-induced nodular regenerative hyperplasia of the liver. The diagnosis was suspected when abnormalities in liver function tests were observed and transabdominal ultrasonography and upper gastrointestinal endoscopy showed signs of portal hypertension. The final diagnosis was established by liver biopsy, showing the characteristic alterations in liver architecture. Outcome was favorable after treatment discontinuation, with complete normalization of liver function tests within a year. The present article describes the incidence and the main clinical characteristics of this adverse effect to thiopurines.

[Use of health resources and loss of productivity in gastroesophageal reflux disease: results of a cross-sectional study in a primary care setting in Spain]. / Consumo de recursos sanitarios y pérdida de productividad en la enfermedad por reflujo gastroesofágico: resultados de un estudio transversal en el ámbito de la atención primaria en España.

OBJECTIVE: To evaluate healthcare resource use and productivity in patients with gastro-esophageal reflux disease (GERD) and the influence of disease severity on these two factors. DESIGN: Sub-analysis of the Spanish population of a multinational study with a 4-month retrospective period for the identification and selection of patients, and a clinical visit to obtain clinical information and data on use of healthcare resources, carried out between October 2007 and January 2008. POPULATION: A total of 477 patients attending a Primary Care centre, with a medical consultation for GERD. MAIN VARIABLES: Use of healthcare resources, changes in productivity based on the Work Productivity and Activity Impairment Questionnaire for GERD patients (WPAI-GERD). RESULTS: Despite having received pharmacological treatment at the baseline visit, after a median of 5.1 months follow-up (range 2.1-8.1), up to 15.9% (95% CI; 12.8-19.5) patients still showed clinically relevant GERD symptoms. Direct medical costs per year associated with diagnostic tests and medical consultations in patients with or without clinically relevant GERD symptoms were 666 € (SD: 2,097 €) and 370 € (SD: 2,060 €), respectively. The mean annual cost of reduced productivity (17%) was 5,316 € (SD: 8,615 €). This cost was 4 times higher for patients with clinically relevant GERD symptoms than for patients with no relevant symptoms (15,188 € [SD: 11,206 €] vs 3,926 € [SD: 7,232 €]). CONCLUSION: Patients with GERD use significant healthcare resources, attributable to associated medical costs and marked reduction in productivity, even though they receive pharmacological treatment.

Liver dysfunction related to hepatitis B and C in patients with inflammatory bowel disease treated with immunosuppressive therapy.

BACKGROUND: There is no information about the frequency of liver dysfunction in patients with inflammatory bowel disease (IBD) treated with immunosuppressants and infected with hepatitis B (HBV) and/or C virus (HCV). AIM: To assess the influence of immunosuppressants on the course of HBV and HCV infection in IBD. METHODS: Patients with IBD with HBV and/or HCV infection from 19 Spanish hospitals were included. Clinical records were reviewed for the type of immunosuppressant used, treatment duration, liver function tests and viral markers before, during and after each immunosuppressant. Logistic and Cox regression analysis were used to identify predictors of outcome. RESULTS: 162 patients were included; 104 had HBV markers (25 HBsAg positive) and 74 had HCV markers (51 HCV-RNA positive), and 16 patients had markers of both infections. Liver dysfunction was observed in 9 of 25 HBsAg positive patients (36%), 6 of whom developed hepatic failure. Liver dysfunction in HCV was observed in 8 of 51 HCV-RNA positive patients (15.7%), and only one developed hepatic failure. The frequency and severity of liver dysfunction was significantly higher in HBV-infected patients than in HCV-infected patients (p=0.045 and p=0.049, respectively). Treatment with ≥2 immunosuppressants was an independent predictor of HBV reactivation (OR 8.75; 95% CI 1.16 to 65.66). The majority of patients without reactivation received only one immunosuppressant for a short period and/or prophylactic antiviral treatment. No definite HBV reactivations were found in anti-HBc positive patients lacking HBsAg. CONCLUSION: Liver dysfunction in patients with IBD treated with immunosuppressants is more frequent and severe in those with HBV than in HCV carriers and is associated with combined immunosuppression.

Usefulness of manometry to select patients with anal fissure for controlled anal dilatation.

AIM: To evaluate the use of anorectal manometry to select patients for controlled anal dilatation. METHODOLOGY: A prospective study was performed using anorectal manometry on all patients with chronic anal fissure who did not have a good response to conservative treatment. Those with increased anal resting pressure were treated with controlled anal dilatation using a two valved anuscope. A second anorectal manometry was indicated after controlled anal dilatation. RESULTS: 19 patients without anorectal pathology (Healthy Control Group) and 57 patients with chronic anal fissure were included in this study. Controlled anal dilatation was performed on 27 patients, maximum resting pressure 122 ± 19 mmHg. In the controlled anal dilatation group the healing rate was 92.5%, mean maximum resting pressure post-controlled anal dilatation was 91 ± 30 mmHg. We found one case of transitory anal incontinence (3.7%). None of the patients had anal incontinence at 18 months of the follow-up. In the remaining 30 patients non selected for controlled anal dilatation (chronic anal fissure control group), a proportion of 53.3% recurrences were registered after conservative treatment. CONCLUSIONS: Anal healing of chronic anal fissure and a significant decrease in maximum resting pressure recorded by manometry confirms the success of this procedure. The manometric evaluation of the maximum resting pressure is useful in the selection of chronic anal fissure patients for controlled anal dilatation. The efficacy of dilatation to treat chronic anal fissure in patients with raised anal sphincter pressure was high and complications were rare.

Effectiveness and Safety of the Switch from Remicade® to CT-P13 in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®. METHODS: Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The 'switch cohort' [SC] comprised patients who made the switch from Remicade® to CT-P13, and the 'non-switch' cohort [NC] patients remained under Remicade®. RESULTS: A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2-6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05]. CONCLUSIONS: Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe.

Real-world short-term effectiveness of ustekinumab in 305 patients with Crohn's disease: results from the ENEIDA registry.

BACKGROUND: There are limited data of ustekinumab administered according to the doses recommended in the UNITI studies. AIM: To assess the real-world, short-term effectiveness of ustekinumab in refractory Crohn's disease (CD) METHODS: Multicentre study of CD patients starting ustekinumab after June 2017 at the recommend dose (260, 390 or 520 mg based on weight ~6 mg/kg IV week 0 and 90 mg subcutaneously week 8). Values for Harvey-Bradshaw Index (HBI), C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8 and 14. Demographic and clinical data, previous treatments, AEs and hospitalisations were documented. Possible predictors of clinical remission were examined. RESULTS: Three hundred and five patients were analysed (≥2 previous anti-TNFα therapies 64% and vedolizumab 29%). At baseline, 217 (72%) had an HBI >4 points. Of these, 101 (47%) and 126 (58%) achieved clinical remission at weeks 8 and 14, respectively. FC levels returned to normal (<250 µg/g) in 46% and 54% of the patients at weeks 8 and 14 respectively. CRP returned to normal (<3 mg/L) in the 35% and 41% of the patients at week 8 and 14 respectively. AEs were recorded in 38, and 40 patients were hospitalised. Intolerance to the most recent anti-TNF agent and fewer previous anti-TNF agents were associated with clinical remission at week 14. Endoscopic severity was associated with poor response. CONCLUSION: This is the first study to show the real-world effectiveness and safety of ustekinumab administered according to the recommended induction regimen in a cohort of highly refractory CD patients.