Treatment patterns and intensification within 5 year of follow-up of the first-line anti-TNFα used for the treatment of IBD: Results from the VERNE study.

BACKGROUND: Anti-TNFα represent one of the main treatment approaches for the management of inflammatory bowel diseases (IBD). Therefore,the evaluation of their treatment patterns over time provides valuable insights about the clinical value of therapies and associated costs. AIMS: To assess the treatment patterns with the first anti-TNFα in IBD. METHODS: Retrospective, observational study. RESULTS: 310 IBD patients were analyzed along a 5-year follow-up period. 56.2% of Crohn's disease (CD) patients started with adalimumab (ADA), while 43.8% started with infliximab (IFX). 12.9% of ulcerative colitis (UC) patients initiated with ADA, while 87.1% initiated with IFX. Treatment intensification was required in 28.9% of CD and 37.1% of UC patients. Median time to treatment intensification was shorter in UC than in CD (5.3 vs. 14.3 months; p = 0.028). Treatment discontinuation due to reasons other than remission were observed in 40.7% of CD and 40.5% of UC patients, although, in UC patients there was a trend to lower discontinuation rates with IFX (36.6%) than with ADA (66.7%). Loss of response accounted for approximately one-third of discontinuations, in both CD and UC. CONCLUSIONS: Around one-third of IBD biologic-naive patients treated with an anti-TNFα required treatment intensification (earlier in UC) and around 40% discontinued the anti-TNFα due to inappropriate disease control.

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.

Phenotype and natural history of elderly onset inflammatory bowel disease: a multicentre, case-control study.

BACKGROUND: Onset during old age has been reported in upto 10% of total cases of inflammatory bowel disease (IBD). AIM: To evaluate phenotypic characteristics and the use of therapeutic resources in patients with elderly onset IBD. METHODS: Case-control study including all those patients diagnosed with IBD over the age of 60 years since 2000 who were followed-up for >12 months, identified from the IBD databases. Elderly onset cases were compared with IBD patients aged 18 to 40 years at diagnosis, matched by year of diagnosis, gender and type of IBD (adult-onset). RESULTS: One thousand three hundred and seventy-four elderly onset and 1374 adult-onset cases were included (62% ulcerative colitis (UC), 38% Crohn's disease (CD)). Among UC patients, elderly onset cases had a lower proportion of extensive disease (33% vs 39%; P < 0.0001). In CD, elderly onset cases showed an increased rate of stenosing pattern (24% vs 13%; P < 0.0001) and exclusive colonic location (28% vs 16%; P < 0.0001), whereas penetrating pattern (12% vs 19%; P < 0.0001) was significantly less frequent. Regarding the use of therapeutic resources, there was a significantly lower use of corticosteroids (P < 0.0001), immunosuppressants (P < 0.0001) and anti-TNFs agents (P < 0.0001) in elderly onset cases. Regarding surgery, we found a significantly higher surgery rate among elderly onset UC cases (8.3% vs 5.1%; P < 0.009). Finally, elderly onset cases were characterised by a higher rate of hospitalisations (66% vs 49%; P < 0.0001) and neoplasms (14% vs 0.5%; P < 0.0001). CONCLUSIONS: Elderly onset IBD shows specific characteristics and they are managed differently, with a lower use of immunosuppressants and a higher rate of surgery in UC.

Efficacy and safety of short-term adalimumab treatment in patients with active Crohn's disease who lost response or showed intolerance to infliximab: a prospective, open-label, multicentre trial.

BACKGROUND: The use of tumour necrosis factor antagonists has changed the therapeutic approach to Crohn's disease. AIM: To determine response and remission rates associated with the 4-week induction phase of adalimumab treatment in patients with luminal and/or fistulizing Crohn's disease, who have lost response to or become intolerant of infliximab. METHODS: In this multicentre, prospective, open-label, observational, 52-week study, 50 adults received an induction dose of adalimumab (160 mg at baseline followed by 80 mg at week 2). RESULTS: Of the 36 patients with luminal Crohn's disease, 83% achieved clinical response [> or =70-point reduction in the Crohn's Disease Activity Index (CDAI) score] and 42% achieved clinical remission (CDAI score <150) at week 4. Of the 22 patients with fistulizing disease, five (23%) experienced fistula remission (complete closure of all fistulas that were draining at baseline), and nine (41%) experienced fistula improvement (> or =50% decrease in the number of fistulas that were draining at baseline) at week 4. Of the 19 adverse events, most [13 (68%)] were mild, and no serious or infectious adverse events occurred. CONCLUSIONS: Adalimumab may be an effective alternative in patients with luminal and/or fistulizing Crohn's disease who have lost response to or become intolerant of infliximab.

Incidence, risk factors and clinical course of thiopurine-induced liver injury in patients with inflammatory bowel disease.

BACKGROUND: The incidence of thiopurine-induced hepatotoxicity in patients with inflammatory bowel disease varies in different studies. AIMS: To assess the rate of thiopurine-induced liver toxicity in patients with inflammatory bowel disease; to determine the predictive factors and to characterize its clinical course and management. METHODS: A cohort of 161 patients was prospectively followed for a median of 271 days. Hepatotoxicity was established when alanine transaminase or alkaline phosphatase plasma levels were greater than twice the upper normal limit. RESULTS: Abnormal liver function was detected in 21 patients (13%; 95% CI: 7-18). Hepatotoxicity occurred in 16 patients (10%; 95% CI: 6-16) after a median of 85 days. In five cases, treatment was withdrawn due to hepatotoxicity. Use of corticosteroids was associated with hepatotoxicity (OR: 4.94; 95% CI: 1.01-23.98) with antitumour necrosis factor concomitant therapy showing a protective role (OR: 0.3; 95% CI: 0.1-3.1). gamma-Glutamyl transferase plasma levels at the onset of hepatotoxicity showed the best predictive value for treatment withdrawal (area under the receiver operating characteristic curve: 0.95). CONCLUSIONS: The incidence of hepatotoxicity in inflammatory bowel disease patients receiving thiopurines is relevant, mainly in patients co-treated with corticosteroids. gamma-Glutamyl transferase plasma level is a useful biomarker in therapy withdrawal prediction.

Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study.

BACKGROUND: Uncontrolled studies suggest that granulocyteaphaeresis might be useful in the management of active ulcerative colitis. AIM: To assess the efficacy of granulocyteaphaeresis treatment in active steroid-dependent inflammatory bowel disease. METHODS: We conducted a multicentre, prospective, open, pilot study in patients with steroid-dependent inflammatory bowel disease. All patients were started on 60 mg/day of prednisone; after 1 week, a five-session programme of granulocyteaphaeresis (once per week) was started. The steroid dose was tapered weekly if there was clinical improvement. Remission was defined as an inactive clinical activity index together with complete withdrawal of steroids at week 6. The patients were followed up for at least 6 months or until disease relapse. RESULTS: Twenty-six patients (14 ulcerative colitis, 12 Crohn's disease) were included. More than a half had been previously treated with immunomodulators. Remission was achieved in 62 and 70% of ulcerative colitis and Crohn's disease, respectively. During a median follow-up of 12.6 months, six of eight ulcerative colitis patients maintained their clinical remission; however, only one Crohn's disease patient remained in remission after the first 6 months of follow-up. CONCLUSIONS: Granulocyteaphaeresis is a safe treatment option in inflammatory bowel disease. A five-session programme of granulocyteaphaeresis seems to be efficient in the treatment of steroid-dependent ulcerative colitis, but not in Crohn's disease.

Receiver operating characteristics curve analysis of factors predictive of nonresponse to interferon therapy in patients with chronic hepatitis C.

OBJECTIVES: 1) to identify pretreatment variables predictive of nonresponse to interferon-alpha (IFN-alpha) in patients with chronic hepatitis C, and 2) to establish a prognostic index in these groups using receiver operating characteristics curve analysis. METHODS: 132 patients were treated with IFN-alpha at a dose of 3 megaunits three times a week for 3-12 months. The response was compared in patients with a complete response vs nonresponders, and patients with a sustained response vs nonresponders plus relapsers. Factors predictive of response were identified by analyzing clinical, biochemical, virological and histological variables. RESULTS: The sustained response rate was 12.8% at 24 months of follow-up. The pretreatment characteristics with a predictive value (PV) according to area under the ROC curve and 95% confidence interval > 0.5 were age, known duration of infection, history of transfusion, GGT, serum ferritin levels, viral load, genotype, and grade and stage of the histological lesion. The positive PV (the probability of predicting absence of response when the variable is present) was notably greater than the negative PV (mean: 94.9% vs 24.8%, respectively). In addition, when 4 and 6 variables were present, the positive PV was 100% and sensitivity was 60.2% and 22.1%, respectively. The predictive variables independently associated with an absence of response were genotypes 1, 4 and 5, GGT > 24 IU/l and grade of the histological lesion > 6. CONCLUSIONS: It was possible to predict the absence of both primary and posttreatment response with an acceptable degree of reliability.

[Factors influencing the decision to administer systemic corticosteroids in Crohn's disease]. / Factores que influyen en la decisión de administrar corticoides sistémicos en la enfermedad de Crohn.

INTRODUCTION: Crohn's disease shows periods of exacerbation and remission. Corticosteroids are the most frequently used drugs in exacerbations of disease activity. The objective of this study is to determine which clinical and laboratory parameters are associated with the therapeutic decision to administer corticosteroids during the course of the disease. MATERIAL AND METHOD: Two-hundred seven consecutive visits made by 62 patients with Crohn's disease were selected from a database. Data from visits in which corticosteroid administration was initiated (n = 65) were compared with those from visits in which this decision was not made (n = 142). Univariate and multivariate (logistic regression) analyses were performed. The results are expressed as odds ratio (OR) with 95% confidence interval (95% CI). RESULTS: In the univariate analysis statistically significant differences were found between groups in localization, maintenance treatment, Crohn's Disease Activity Index (CDAI) score, the presence of abdominal pain, mass, perianal disease, extraintestinal manifestations and all laboratory parameters (leukocytes, platelets, fibrinogen, erythrocyte sedimentation rate, C-reactive protein). In the multivariate analysis (with corticosteroid administration as the dependent variable) a statistically significant positive association was found between the decision to administer corticosteroids and mild (OR = 31.9; 95% CI, 6.6-154.1), moderate or severe (OR = 49.7; 95% CI, 6.1-401.3) CDAI, ileocolic localization (OR = 4.8; 95% CI, 1-22.1) and the presence of perianal disease (OR = 7.4; 95% CI, 1.5-35.9), while a negative association was found with maintenance treatment with immunosuppressant drugs (OR = 0.05; 95% CI, 0.30-0.008). The laboratory variables positively associated with corticosteroid administration were C-reactive protein and leukocyte count. CONCLUSION: The variable with greatest predictive value for corticosteroid prescription is the CDAI score, although other clinical and laboratory variables not included in this index are also associated with corticosteroid administration. There is a negative association between the use of immunosuppressive drugs and corticosteroid prescription.

[Endoscopic treatment of pancreatitis and its complications]. / Tratamiento endoscópico de la pancreatitis y sus complicaciones.

OBJECTIVES: To study the long- and short-term safety and efficacy of endoscopic treatment of pancreatitis and its complications in our environment. PATIENTS AND METHODS: We performed a retrospective analysis of 43 patients with chronic pancreatitis, acute pancreatitis complicated with pseudocyst, and pancreatic fistula diagnosed by endoscopic retrograde cholangiopancreatography who were suitable for endoscopic treatment. RESULTS: Endoscopic treatment was attempted in 35 patients. The indication for treatment was pain in 17 patients (48.5%), jaundice in 7 (20%), pseudocyst in 10 (28.5%) and suspected external fistula in 1 (3%). The technique was successfully performed in 28 (80%). Of the patients with pain, pancreatic prosthesis was inserted in 13 and extracorporeal lithotripsy was applied in 6. Sixty-five percent of the patients improved. Of the 7 patients with jaundice, all had secondary stenosis of the biliary tract. Treatment was applied in 2, who showed partial improvement. Of the 15 patients with pseudocyst, endoscopic treatment was indicated in 10; the technique was successfully performed in 8 and complete resolution was achieved in 7 (87.5%). The patient with external fistula was treated with transpapillary prosthesis and complete resolution of disruption of Wirsung's duct was achieved. Overall improvement in successfully treated patients was: complete in 19 (68%), partial in 3 (18%), no improvement in 4 (14%) and 2 patients were lost to treatment. There were 4 short-term complications. There were 4 deaths and one was related to the technique. CONCLUSIONS: Endoscopic treatment of chronic pain in chronic pancreatitis, pseudocysts and fistulas was effective in our environment with a low rate of complications.

[Endoscopic treatment combined with extracorporeal shock wave lithotripsy of difficult bile duct stones]. / Tratamiento endoscópico combinado con litotricia extracorpórea con ondas de choque de la coledocolitiasis de difícil manejo.

OBJECTIVES: The aim of this study was to determine the safety and effectiveness of extracorporeal shock wave lithotripsy (ESWL) in difficult bile duct stones resistant to endoscopic extraction. PATIENTS AND METHOD: From January 1997 to February 2002, combined treatment with endoscopy and ESWL was used in 19 patients who had undergone unsuccessful endoscopic bile duct stone extraction after sphincterotomy. The procedure was carried out using analgesic and sedative drugs or deep sedation, prophylactic antibiotic therapy, and monitoring of vital signs. Bile duct stone localization was performed by contrast injection through nasobiliary drainage and fluoroscopy. After each ESWL session, lavage was performed through drainage and stone fragments were extracted endoscopically. RESULTS: The 19 patients presented high surgical risk due to advanced aged and/or concomitant diseases. All presented jaundice and pain and nine (47.3%) presented associated cholangitis. Thirty ESWL sessions were performed (1.57 sessions per patient), with a mean of 2,120 shock waves per session. In 16 of the 19 patients (84.2%), combined treatment with ESWL and subsequent instrumental endoscopic extraction achieved complete clearance of the biliary tract. The treatment failed in 3 patients who were referred for surgical treatment. No early or late complications were observed, except in one patient who presented a self-limiting febrile syndrome. CONCLUSIONS: Therapeutic endoscopy combined with ESWL is safe and effective in patients with difficult bile duct stones. It represents a therapeutic alternative in patients at high surgical risk.

Infliximab salvage therapy after failure of ciclosporin in corticosteroid-refractory ulcerative colitis: a multicentre study.

BACKGROUND: Ciclosporin has proven to be effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with this drug fails, infliximab can be considered to avoid colectomy. The efficacy and safety of this sequential approach remain unknown. AIM: To assess the efficacy and safety profile of treatment with infliximab after failure of ciclosporin in patients with a corticosteroid-refractory flare of UC. METHODS: Retrospective review of medical records of patients with a corticosteroid-refractory flare of UC who did not respond to ciclosporin and received salvage therapy with infliximab within a month of discontinuing ciclosporin. The severity of the flare and response to the treatment were graded using the Lichtiger index. Cumulative rates of colectomy were calculated using Kaplan-Meier analysis. Cox regression analysis was performed to identify predictors of colectomy. To evaluate the safety profile of this treatment strategy, any adverse event occurring after the first infusion of infliximab was considered. RESULTS: The study population comprised 47 patients with corticosteroid-refractory UC treated with infliximab after failure of ciclosporin. The median baseline Lichtiger index was 13. The mean time from the last ciclosporin dose to the first infliximab infusion was 6 days. After the first infliximab infusion, 13% of patients achieved remission, and 74% partial response. Of the 35 patients who received the third infliximab infusion, 60% achieved remission, and 37% partial response. Fourteen patients (30%) underwent colectomy. The rate of adverse events was 23%. One death occurred in a 40-year-old man who failed ciclosporin and infliximab and underwent surgery 10 days after the first infliximab infusion; he died of nosocomial pneumonia. CONCLUSIONS: Treatment with infliximab makes it possible to avoid colectomy in two-thirds of corticosteroid-refractory UC patients in whom ciclosporin fails. However, the rates of adverse events and mortality mean that the decision to administer sequential therapy (ciclosporin-infliximab) should be taken on an individual basis.

Adalimumab induction and maintenance therapy for patients with ulcerative colitis previously treated with infliximab.

BACKGROUND: The long-term efficacy of adalimumab in patients with ulcerative colitis is not well known. AIM: To evaluate the short- and long-term outcomes of adalimumab in ulcerative colitis patients previously treated with infliximab. METHODS: Patients with active ulcerative colitis were treated with adalimumab after failure of other therapies including infliximab. Short-term clinical response and remission were assessed at weeks 4 and 12. The proportion of patients who continued on adalimumab and the proportion of patients who remained colectomy free were assessed over the long term. RESULTS: Clinical response at weeks 4 and 12 was achieved in 16 (53%) and 18 (60%) patients, respectively, and clinical remission was obtained in 3 (10%) and 8 (27%) patients, respectively. After a mean 48 weeks' follow-up, 15 patients (50%) continued on adalimumab. Six patients (20%) required colectomy. All patients who achieved clinical response at week 12 were colectomy free at long term. CONCLUSIONS: Adalimumab was well tolerated and induced durable clinical response in many patients with otherwise medically refractory ulcerative colitis. Patients achieving clinical response at week 12 avoided colectomy over the long term.

Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations.

BACKGROUND: The risks and benefits of coxibs, non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin treatment are under intense debate. OBJECTIVE: To determine the risk of peptic ulcer upper gastrointestinal bleeding (UGIB) associated with the use of coxibs, traditional NSAIDs, aspirin or combinations of these drugs in clinical practice. METHODS: A hospital-based, case-control study in the general community of patients from the National Health System in Spain. The study included 2777 consecutive patients with endoscopy-proved major UGIB because of the peptic lesions and 5532 controls matched by age, hospital and month of admission. Adjusted relative risk (adj RR) of UGIB determined by conditional logistic regression analysis is provided. RESULTS: Use of non-aspirin-NSAIDs increased the risk of UGIB (adj RR 5.3; 95% confidence interval (CI) 4.5 to 6.2). Among non-aspirin-NSAIDs, aceclofenac (adj RR 3.1; 95% CI 2.3 to 4.2) had the lowest RR, whereas ketorolac (adj RR 14.4; 95% CI 5.2 to 39.9) had the highest. Rofecoxib treatment increased the risk of UGIB (adj RR 2.1; 95% CI 1.1 to 4.0), whereas celecoxib, paracetamol or concomitant use of a proton pump inhibitor with an NSAID presented no increased risk. Non-aspirin antiplatelet treatment (clopidogrel/ticlopidine) had a similar risk of UGIB (adj RR 2.8; 95% CI 1.9 to 4.2) to cardioprotective aspirin at a dose of 100 mg/day (adj RR 2.7; 95% CI 2.0 to 3.6) or anticoagulants (adj RR 2.8; 95% CI 2.1 to 3.7). An apparent interaction was found between low-dose aspirin and use of non-aspirin-NSAIDs, coxibs or thienopyridines, which increased further the risk of UGIB in a similar way. CONCLUSIONS: Coxib use presents a lower RR of UGIB than non-selective NSAIDs. However, when combined with low-dose aspirin, the differences between non-selective NSAIDs and coxibs tend to disappear. Treatment with either non-aspirin antiplatelet or cardioprotective aspirin has a similar risk of UGIB.

[Suprapubic bladder aspiration. Utility and complication]. / Punción vesical suprapúbica. Utilidad y complicaciones.

OBJECTIVE: This study aims at evaluating the usefulness of suprapubic bladder aspiration (SBA) in order to diagnose urinary tract infection (UTI), enumerating the complications and describes those found in the existing literature. PATIENTS AND METHODS: We have reviewed the 668 SBAs carried out on 642 children over a period of 3 years. The ages of the children varied from neonate to 5 years. Urine cultures were regarded as positive when any one single germ showed bacterial growth signs. RESULTS: Ninety-four UTIs, 14.6% of the total samples studied, were detected, five of which were in newborns. Infection by Escherichia coli comprised 87.2% of the total. Two complications were observed: needle breakage and vaginal bleeding. CONCLUSIONS: SBA is a reliable method, with hardly any complications, and is essential for the accurate diagnosis of UTI. However, it must be used with a more restrictive criterion in the neonatal period.

Análisis mediante las curvas ROC de los factores predictivos de no respuesta al tratamiento con interferón en pacientes con hepatitis crónica C / Receiver operating characteristics curve analysis of factors predictive of nonresponse to interferon therapy in patients with chronic hepatitis C

OBJETIVO: 1) identificar variables pretratamiento predictivas de no respuesta en 132 pacientes con hepatitis crónica C tratados con IFN-a con una dosis de 3 MU/3 vs/ 3-12 meses, comparando pacientes no respondedores más recaedores frente a pacientes respondedores sostenidos, y 2) establecer en este grupo un índice pronóstico mediante análisis con las curvas ROC. RESULTADOS: la tasa de respuesta sostenida fue del 12, 8 por ciento a los 24 meses de seguimiento. La edad, la duración conocida de la infección, el antecedente de transfusión, la GPT, la GGT, los niveles de ferritina sérica, la carga viral, el genotipo, el grado y el estadio de la lesión histológica fueron las características pretratamiento con valor predictivo (VP, área bajo la curva ROC e intervalo de confianza al 95 por ciento > 0,5). El valor predictivo positivo (la probabilidad de predecir la ausencia de respuesta cuando la variable está presente) es sensiblemente mayor que el VP negativo (media: 94,9 por ciento vs 24,8 por ciento). Por otro lado, la probabilidad de predecir la ausencia de respuesta cuando cuatro y seis variables estaban presentes fue del 100 por ciento y la sensibilidad fue del 60,2 y 22,1 por ciento, respectivamente. El genotipo 1, 4 y 5, los valores de GGT mayor a 24 Ul/l y el grado de lesión histológica mayor a seis fueron las variables con asociación pronóstica independiente con la ausencia de respuesta. CONCLUSIONES: es posible predecir con un grado de fiabilidad aceptable la ausencia de respuesta, tanto primaria como postratamiento (AU)