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BACKGROUND & AIMS: Due to the poor eradication rates of standard triple therapy, the addition of bismuth salts has been proposed for first-line eradication of Helicobacter pylori. We assessed the effectiveness and safety of the combination of bismuth and the standard, clarithromycin-containing triple therapy in eradication of H pylori infection, using data from a large multi-center registry. METHODS: We performed an interim analysis of data from the European Registry on H pylori Management, a prospective trial registering clinical data and outcomes from infected patients from 27 countries in Europe since 2013. We extracted data on 1141 treatment-naïve patients who received first-line treatment with bismuth salts (240 mg) and a proton pump inhibitor (57% received esomeprazole, 18% received omeprazole, 11% received pantoprazole, and 14% received rabeprazole), amoxicillin (1 g), and clarithromycin (500 mg), all taken twice daily. RESULTS: Intention to treat and per-protocol rates of eradication were 88% and 94%, respectively. Intention to treat eradication increased to 93% in patients who received 14-day treatments. Adverse events occurred in 36% of patients; 76% of these events were mild, with a mean duration of 6 days. In multivariate analysis, eradication was associated with treatment compliance (odds ratio [OR], 13.0), a double dose (equivalent to 40 mg omeprazole) of proton pump inhibitor (OR, 4.7), and 14-day duration of treatment (OR, 2.0). CONCLUSIONS: In an analysis of data from a large multi-center registry, we found the addition of bismuth to 14-day standard triple therapy with clarithromycin and amoxicillin to eradicate H pylori infection in more than 90% of patients, based on intention to treat analysis, with an acceptable safety profile and level of adherence. ClinicalTrials.gov no: NCT02328131.
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Amoxicilina/administración & dosificación , Antiinfecciosos/administración & dosificación , Bismuto/administración & dosificación , Claritromicina/administración & dosificación , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Farmacorresistencia Bacteriana Múltiple , Quimioterapia Combinada , Europa (Continente) , Femenino , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/virología , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/administración & dosificación , Sistema de Registros , Resultado del Tratamiento , Adulto JovenRESUMEN
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.
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Anticuerpos contra la Hepatitis B/inmunología , Vacunas contra Hepatitis B/uso terapéutico , Hepatitis B/prevención & control , Inmunosupresores/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Corticoesteroides/uso terapéutico , Adulto , Quimioterapia Combinada , Femenino , Vacunas contra Hepatitis B/inmunología , Humanos , Inmunogenicidad Vacunal , Enfermedades Inflamatorias del Intestino/inmunología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: At present only monoclonal EIA (enzyme-immunoassay) stool antigen-tests have obtained optimal accuracy in the diagnosis of Helicobacter pylori. Our aim was to evaluate the accuracy of two stool antigen-tests, the validated Premier Platinum HpSA PLUS (EIA test) and the newly available ImmunoCard STAT! HpSA HD (rapid test) for the initial diagnosis and the confirmation of eradication of H. pylori infection. PATIENTS AND METHODS: Patients with indication of H. pylori diagnosis, or confirmation after treatment were included. Data were coded to protect personal data and ensure blindness between tests. Accuracy was considered as coincident diagnosis with the gold standard (13C-urea breath test, UBT). The EIA was used as a bench standard. All stool tests were performed in duplicate. RESULTS: 264 patients completed the protocol (100 naïve, 164 post-eradication). Average age was 52 years, 61% women, 11% ulcer. Positive diagnoses by UBT were 41% for naïve and 17% for post-eradication. Overall ImmunoCard and EIA accuracies were respectively 91% (95%C.I.=88-94%) and 89% (86-93%), sensitivities 72% (67-78%) and 72% (67-78%), and specificities 98% (96-100%), and 95% (92-97%). Concordance between ImmunoCard and EIA was 95% (93-98%). DISCUSSION: Our results indicate that the newly available ImmunoCard rapid stool antigen-test achieves 90% accuracy, with high specificity but suboptimal sensitivity. The ImmunoCard attained equivalent accuracies as the EIA bench standard, with 95% concordance.
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Antígenos Bacterianos/análisis , Heces/microbiología , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/inmunología , Inmunoensayo/métodos , Técnicas para Inmunoenzimas/métodos , Juego de Reactivos para Diagnóstico , Anciano , Área Bajo la Curva , Pruebas Respiratorias , Dispepsia/microbiología , Heces/química , Femenino , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Úlcera Péptica/microbiología , Estudios Prospectivos , Curva ROC , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: (a) To evaluate the diagnostic accuracy of anti-TNF trough levels to predict mucosal healing in inflammatory bowel disease (IBD); (b) to determine the best cut-off point to predict mucosal healing in IBD patients treated with anti-TNF. METHODS: This is a multicenter, prospective study. IBD patients under anti-TNF treatment for at least 6 months that had to undergo an endoscopy were included. Mucosal healing was defined as: Simple endoscopic score for Crohn's Disease < 3 for Crohn's disease (CD), Rutgeerts score < i2 for CD in postoperative setting, or Mayo endoscopic score ≤ 1 for ulcerative colitis (UC). Anti-TNF concentrations were measured using SMART ELISAs at trough. RESULTS: A total of 182 patients were included. Anti-TNF trough levels were significantly higher among patients that had mucosal healing than among those who did not. The area under the curve of infliximab for mucosal healing was 0.63 (best cutoff value 3.4 µg/mL), and for adalimumab 0.60 (best cutoff value 7.2 µg/mL). In the multivariate analysis, having anti-TNF drug levels above the cutoff values [odds ratio (OR) 3.1]) and having UC instead of CD (OR 4) were associated with a higher probability of having mucosal healing. Additionally, the need for an escalated dosage (OR 0.2) and current smoking habit (OR 0.2) were also associated with a lower probability of mucosal healing. CONCLUSIONS: There was an association between anti-TNF trough levels and mucosal healing in IBD patients; however, the accuracy of the determination of infliximab and adalimumab concentrations able to predict mucosal healing was suboptimal.
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Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Productos Biológicos/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Infliximab/uso terapéutico , Mucosa Intestinal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Cicatrización de Heridas/efectos de los fármacos , Adalimumab/sangre , Adalimumab/farmacocinética , Adulto , Antiinflamatorios/sangre , Antiinflamatorios/farmacocinética , Productos Biológicos/sangre , Productos Biológicos/farmacocinética , Colitis Ulcerosa/sangre , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/sangre , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/inmunología , Monitoreo de Drogas/métodos , Endoscopía Gastrointestinal , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Infliximab/sangre , Infliximab/farmacocinética , Mucosa Intestinal/inmunología , Mucosa Intestinal/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , España , Factores de Tiempo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
BACKGROUND: Helicobacter pylori (H. pylori) is the most common chronic bacterial infection in the world affecting over 50% of the world's population. H. pylori is a grade I carcinogen, responsible for the development of 89 % of noncardia gastric cancers. In the present study we analyzed the data for H. pylori eradication treatments in Slovenia. PATIENTS AND METHODS: Slovenia is a part of the European Registry on Helicobacter pylori Management from the beginning. In seven medical institutions data for H. pylori eradication treatments was collected for 1774 patients from April 16th 2013 to May 15th 2016. For further modified intention to treat (mITT) analysis 1519 patients were eligible and for per protocol (PP) analysis 1346 patients. RESULTS: Patients' dropout was 11.4%. Eradication rate for 7 day triple therapy with proton pump inhibitor (PPI) + Clarithromycin (C) + Amoxicillin (A) was 88.7% PP and 72.0% mITT; for PPI + C + Metronidazole (M) 85.2% PP and 84.4% mITT. Second line 14 day therapy PPI + A + Levofloxacin had 92.3% eradication rate PP and 87.1% mITT. Ten to fourteen day Bismuth quadruple therapy was the therapy in difficult to treat patients. At the end all patients that adhered to prescribed regimens were cured of their H. pylori infection. CONCLUSIONS: High dropout rate deserves further analysis. Slovenia is still a country with < 15% H. pylori resistance to clarithromycin, triple therapy with PPI plus two antibiotics reaches PP eradication rate > 85%, but mITT eradication rates are suboptimal.
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BACKGROUND: A progressive decrease in Helicobacter pylori eradication rates has been described over the years, driving the need for new antibiotic treatments. AIM: To evaluate the efficacy and safety of the addition of rifaximin (Spiraxin®) to standard triple therapy (omeprazole, amoxicillin and clarithromycin) for the eradication of H. pylori. METHODS: Independent prospective clinical trial (EUDRACT no.: 2013-001080-23). Forty consecutive adult patients were included with H. pylori infection, dyspeptic symptoms and naive to eradication treatment. A full blood test was performed in the first five patients enrolled to evaluate the safety of the treatment. H. pylori eradication was confirmed with the 13C-urea breath test at least four weeks after the end of treatment with rifaximin 400mg/8h, clarithromycin 500mg/12h, amoxicillin 1g/12h and omeprazole 20mg/12h for 10 days. RESULTS: Forty patients were consecutively enrolled, 53% woman, mean age 44 years. Indication for eradication: 60% non-investigated dyspepsia, 38% functional dyspepsia and 2% gastric ulcer. Four patients did not attend the eradication confirmatory breath test. The eradication rate was 61% (95% CI: 45-77%) for the protocol and 55% (40-70%) for intention-to-treat. About 76% of the patients experienced adverse events (35% diarrhea, 14% nausea and 24% metallic taste), none of which was serious. The blood tests did not show significant alterations. CONCLUSION: Acceptable H. pylori eradication rates are not achieved with rifaximin associated with standard triple therapy for 10 days.
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Amoxicilina/administración & dosificación , Antiinfecciosos/administración & dosificación , Antiulcerosos/administración & dosificación , Claritromicina/administración & dosificación , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Omeprazol/administración & dosificación , Rifamicinas/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Amoxicilina/efectos adversos , Antiinfecciosos/efectos adversos , Antiulcerosos/efectos adversos , Claritromicina/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/efectos adversos , Proyectos Piloto , Estudios Prospectivos , Rifamicinas/efectos adversos , Rifaximina , Resultado del Tratamiento , Adulto JovenRESUMEN
The stool antigen test (SAT) represents an attractive alternative for detection of Helicobacter pylori. The aim of this study was to assess the accuracy of a new SAT, the automated LIAISON® Meridian H. pylori SA based on monoclonal antibodies, compared to the defined gold standard 13C-urea breath test (UBT). This prospective multicentre study (nine Spanish centres) enrolled patients ≥18 years of age with clinical indication to perform UBT for the initial diagnosis and for confirmation of bacterial eradication. Two UBT methods were used: mass spectrometry (MS) including citric acid (CA) or infrared spectrophotometry (IRS) without CA. Overall, 307 patients (145 naïve, 162 with confirmation of eradication) were analysed. Using recommended cut-off values (negative SAT < 0.90, positive ≥ 1.10) the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 67%, 97%, 86%, 92% and 91%, respectively, obtaining an area under the receiver operating characteristic (ROC) curve (AUC) of 0.85. Twenty-eight patients, including seven false positives and 21 false negatives, presented a discordant result between SAT and UBT. Among the 21 false negatives, four of six tested with MS and 11 of 15 tested with IRS presented a borderline UBT delta value. In 25 discordant samples, PCR targeting H. pylori DNA was performed to re-assess positivity and SAT accuracy was re-analysed: sensitivity, specificity, positive predictive value, negative predictive value, accuracy and AUC were 94%, 97%, 86%, 99%, 97% and 0.96, respectively. The new LIAISON® Meridian H. pylori SA SAT showed a good accuracy for diagnosis of H. pylori infection.
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BACKGROUND: Active disease during conception and pregnancy in women with inflammatory bowel disease (IBD) increases the risk of pregnancy complications and adverse neonatal outcomes. The use of IBD treatments during pregnancy should be weighed against their adverse effects on the neonate, but longer-term safety data and data on serious infection rates and malignancies postnatally are lacking, particularly for newer drugs, such as tofacitinib, vedolizumab and ustekinumab. METHODS: This ongoing, prospective registry study being conducted at 70 centres in Spain is enrolling pregnant women who are ⩾18 years, are at any point in pregnancy up to the end of the second trimester and have a diagnosis of Crohn's disease, ulcerative colitis or unclassified IBD. Patients will receive treatment decided independently by their IBD specialist. Each incident gestation will be followed up through pregnancy and the first 4 years postnatally. Three cohorts will be compared: biologicals exposed, immunomodulatory exposed and non-exposed. The primary endpoint is the risk of severe infection in newborns postnatally up to 4 years of age; other endpoints include serious adverse events (SAEs) such as pregnancy and delivery complications, neonatal SAEs, development [Ages and Stages Questionnaire-3 (ASQ3)], and malignancy incidence, up to 4 years of age. IBD specialists will collect maternal data (baseline/end of each trimester/1 month post-delivery), neonatal birth data, and the SAE and ASQ3 data in children exposed during pregnancy, reported every 3 months by the mother. Statistical analysis will include summary statistics for quantitative variables, comparisons of qualitative variables with significance set at p < 0.025 and a binary logistic regression model to determine the risk factors for severe infections. RESULTS: Enrolment began in September 2019 and study completion is expected in September 2028. CONCLUSIONS: This prospective, controlled study will provide evidence on the long-term safety profile in children after intrauterine and lactation exposure to biological and immunomodulatory IBD treatments, including data on postnatal severe infections, development and malignancies. CLINICALTRIALSGOV IDENTIFIER: NCT03894228.
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BACKGROUND: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1 year in patients who discontinue anti-TNF treatment versus those who continue treatment. METHODS: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn's disease or ulcerative colitis who have achieved clinical remission for ⩾6 months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1 year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. RESULTS: Enrolment began in 2016, and the study is expected to end in 2020. CONCLUSIONS: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. CLINICAL TRIAL REFERENCE NUMBER: EudraCT 2015-001410-10.