Is safety infliximb during pregnancy in patients with inflammatory bowel disease?

BACKGROUND: in most cases, inflammatory bowel disease (IBD) debuts at reproductive age. The data available in the literature show infliximab (IFX) to be a safe drug during pregnancy but there is very little evidence about the activity of the disease following drug withdrawal during pregnancy. AIMS: determine the drug's safety in pregnant women in our setting and assess its effect on the foetus, drawing on the experience of several hospitals. Secondly, observe the effect of treatment withdrawal on disease activity during pregnancy. MATERIAL AND METHODS: a retrospective study was conducted of women with IBD who had received IFX treatment during pregnancy in five hospitals in Spain. Disease activity was assessed using Crohn's Disease Activity Index, while UC was assessed using the Truelove-Witts Index in each trimester of pregnancy. Gestational age, weight and diseases in the foetus were determined at birth. RESULTS: the study included 12 women with a mean age of 29 years; 4 had ulcerative colitis and 8 Crohn's disease, with mean disease duration of 7 years. All but one, who was diagnosed during pregnancy, was receiving IFX treatment at conception. Six patients received uninterrupted treatment throughout the pregnancy, 2 requested voluntary interruption and in 3 cases treatment was interrupted in the third trimester as a precaution. They received a mean IFX dose of 400 mg every 8 weeks. Of the 6 patients who received continuous treatment, in 50% disease was held in remission. The 6 remaining patients suspended treatment for different reasons, presenting disease recurrence in all but one case (83.3%). Eight deliveries were vaginal and 4 by caesarean section. Newborns presented no congenital anomalies, intrauterine growth retardation or low birth weight and there was only one premature delivery. CONCLUSIONS: although cases included in the study are not significant, in our experience, IFX during pregnancy is a safe treatment for the mother and the foetus. In fact, in our study and in some cases, its withdrawal may lead to a worsening of the disease. However, further control studies are required with larger samples to obtain more representative findings.

Role of serum cytokine profile in ulcerative colitis assessment.

BACKGROUND: Several cytokines are overexpressed in the colonic mucosa of patients with ulcerative colitis (UC). The measurement of these parameters in plasma could be useful in diagnosis and disease assessment. METHODS: In all, 67 UC patients and 21 healthy controls were enrolled. At inclusion, clinical, endoscopic, and histological disease activity were assessed using the Ulcerative Colitis Activity Index (UCAI) and the Baron and Geboes scales, respectively. Serum cytokine concentrations were analyzed with a multiplex system (Bio-Plex pro, Bio-Rad) measuring interleukin (IL)-1-ß, IL-2, IL-6, IL-8, IL-10, IL-13, IL-17, interferon-gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α). Multiple logistic regression was used to design a serum cytokines profile. RESULTS: In the UC group the disease activity was moderate to severe based on clinical evaluation in 35 patients (52.2%), by endoscopic appearance in 45 (67.2%), and in 53 patients (81.6%) using histology. With respect to controls, the multivariate analysis identified that UC patients had higher IL-8 (odds ratio [OR] = 1.37; P = 0.002) and IL-10 concentrations (OR = 3.88; P = 0.012) with lower levels of IFN-γ (OR = 0.95; P = 0.002). The model had an accuracy of 77.3%, which increased to 94.6% when only newly diagnosed patients were considered. Patients with moderate to severe disease according to their clinical score showed a higher concentration of IL-8 (OR = 1.16; P = 0.012) and IL-10 (OR = 1.76; P = 0.039) with lower levels of IL-17 (OR = 0.97; P = 0.021). The IL-8 serum concentration was also related to endoscopic and histological severity (OR = 1.10; P = 0.026 and OR = 1.33, P = 0.017, respectively). CONCLUSIONS: A serum cytokine profile may be an auxiliary tool for the diagnosis and severity assessment of UC. IL-8 seems to be a reliable biomarker, closely related to disease activity.

Clinical patterns and outcomes of ischaemic colitis: results of the Working Group for the Study of Ischaemic Colitis in Spain (CIE study).

BACKGROUND: There is a lack of prospective studies evaluating the natural history of colonic ischaemia (CI). We performed such a study to evaluate the clinical presentation, outcome, and mortality as well as clinical variables associated with poor prognosis. METHODS: An open, prospective, and multicentre study was conducted in 24 Spanish hospitals serving a population of 3.5 million people. The study included only patients who met criteria for definitive or probable CI. A website (www.colitisisquemica.org) provided logistical support. RESULTS: A total of 364 patients met criteria for inclusion. CI was suspected clinically in only 24.2% of cases. The distribution of clinical patterns was as follows: reversible colopathy (26.1%), transient colitis (43.7%), gangrenous colitis (9.9%), fulminant pancolitis (2.5%), and chronic segmental colitis (17.9%). A total of 47 patients (12.9%) had an unfavorable outcome as defined by mortality and/or the need for surgery. Multivariate analysis identified the following signs as independent risk factors for an unfavorable outcome: abdominal pain without rectal bleeding [odds ratio (OR) 3.9; 95% confidence interval (CI) = 1.6-9.3], non-bloody diarrhoea (OR 10; 95% CI = 3.7-27.4), and peritoneal signs (OR 7.3; 95% CI = 2.7-19.6). Unfavorable outcomes also were more frequent in isolated right colon ischaemia (IRCI) compared with non-IRCI (40.9 vs. 10.3%, respectively; p < 0.0001). The overall mortality rate was 7.7%. CONCLUSIONS: The clinical presentation of CI is very heterogeneous, perhaps explaining why clinical suspicion of this disease is so low. The presence of IRCI, and occurrence of peritoneal signs or onset of CI as severe abdominal pain without bleeding, should alert the physician to a potentially unfavorable course.

Does fecal calprotectin predict relapse in patients with Crohn's disease and ulcerative colitis?

BACKGROUND AND AIMS: An evaluation is made of the utility of fecal calprotectin in predicting relapse in patients with inflammatory bowel disease (IBD). The possible differences in its predictive capacity in Crohn's disease (CD) versus ulcerative colitis (UC), and the different phenotypes, are also examined. METHODS: This is a prospective study with 135 patients diagnosed with IBD in clinical remission for at least 3 months. The patients submitted a stool sample within 24 hours after the baseline visit, for the measurement of fecal calprotectin. All patients were followed-up on for one year. RESULTS: Sixty-six patients had CD and 69 UC. Thirty-nine (30%) suffered from relapse. The fecal calprotectin concentration was higher among the patients with relapse than in those that remained in remission: 444 µg/g (95% CI 34-983) versus 112 µg/g (95% CI 22-996); p<0.01. Patients with CD and calprotectin>200 µg/g relapsed 4 times more often than those with lower marker concentrations. In UC, calprotectin>120 µg/g was associated with a 6-fold increase in the probability of disease activity outbreak. The predictive value was similar in UC and CD with colon involvement and inflammatory pattern. In this group, calprotectin>120 µg/g predicted relapse risk with a sensitivity of 80% and a specificity of 60%. Relapse predictive capacity was lower in patients with ileal disease. CONCLUSIONS: Fecal calprotectin may be a useful marker for predicting relapse in patients with IBD. Its predictive value is greater in UC and CD with colon involvement and inflammatory pattern, compared with ileal CD.

Can systemic cytokines predict relapse of inflammatory bowel disease?

BACKGROUND/AIMS: To determine the value of systemic cytokines as predictors of relapse in inflammatory bowel disease (IBD). METHODOLOGY: A prospective study with 135 patients in clinical remission for at least 3 months. At enrollment, a venous blood was drawn in order to measure, by an ELISA test, the following cytokines: TNFalpha, TNFalpha-R1 and R2, IL-16, IL-1beta, IL 2, IL-R2, IL-6, IL-10, and IFNgamma. All patients were followed-up for one year. RESULT: Sixty-six patients had Crohn's disease (CD) and 69 had ulcerative colitis (UC). Thirty-nine (30%) had a relapse. Forty-four percent were receiving immunomodulatory therapy. No differences were found regarding detection and baseline concentration of the various cytokines between patients with CD and UC, or between patients with or without ongoing use of immunomodulators. The detection and concentration levels of cytokines were not associated with the risk of relapse of IBD. CONCLUSIONS: Systemic cytokines are of little value to predict IBD relapse.

Infliximab maintenance therapy is associated with decreases in direct resource use in patients with luminal or fistulizing Crohn's disease.

GOALS: To estimate the impact of infliximab (IFX) maintenance therapy on the use of hospital resources in patients with Crohn's disease (CD). STUDY: Medical records of patients treated with IFX maintenance therapy (5 mg/kg body weight; intravenous infusion) for luminal (L) or fistulizing (F) CD at 13 hospitals were retrospectively reviewed. Patients were assessed as their own controls. Use of CD-related healthcare resources was recorded comparing 1-year periods before and after first IFX infusion (pre-IFX and post-IFX). RESULTS: One hundred fifty-three CD patients (n=84 L; 69 F) fulfilled the inclusion criteria. Mean number of IFX infusions was 7/y with an average of 335 mg/infusion dose/patient. During the pre-IFX period, 55% of patients needed hospitalization versus 31% in the post-IFX period (P<0.001). Mean inpatient stay was 11.3 d/y [11.2 (L), 11.5 (F)] for the pre-IFX period, and 6.3 d/y [6.2 (L), 6.3 (F)] in the post-IFX period (P<0.001). Surgery was required in 24% patients in the pre-IFX period and in 11% post-IFX (P<0.001). There were no significant changes in the incidence of outpatient visits although emergency room visits fell significantly. CONCLUSIONS: Maintenance IFX in CD patients is associated with decreases in the use and length of hospitalizations and the need for surgery in clinical practice.

[Adequate rate of response to hepatitis B virus vaccination in patients with inflammatory bowel disease]. / Eficacia de la vacuna contra el virus de la hepatitis B en pacientes con enfermedad inflamatoria intestinal.

BACKGROUND AND OBJECTIVE: Patients with Inflammatory Bowel Disease (IBD) may have an increased risk of developing hepatitis B virus (HB) infection. Invasive procedures such as colonoscopies and surgery might be some of the reasons for this. Moreover, the use of immunosuppressors may reactivate a latent infection. We assessed the immune status among IBD patients receiving HB vaccine and the circumstances that predicted its results. AIMS AND METHODS: Serological markers of B and C hepatitis virus in patients with IBD who were referred for consultation were assessed since 2006. The subsequent determination of antibodies against superficial antigen (HBsAb) could differentiate between responders and non responders to the vaccine and an adequate immunity to HB was defined as higher than 10mUI/ml. RESULTS: One hundred and twenty nine patients were included in our study. Fifty-six (43,4%) patients had received immunosuppressive medication before the first vaccine dose. Notably, 85 (65.9%) patients had inadequate levels of HBsAb: 36 had no detectable levels and 49 had less than 10mUI/ml. Younger patients had a better immunity response than older patients (30.91+/-14.8 vs 39.91+/-14.2) (p<0.001). CONCLUSION: More than half of the patients had a suboptimal serologic response after vaccination. Only the younger group showed a better rate of response. It was not demonstrated whether an additional fourth dose of vaccination or a complete revaccination improved the rate of responders.

[Diagnostic value of fecal calprotectin in predicting an abnormal colonoscopy]. / Precisión diagnóstica de la calprotectina fecal para predecir una colonoscopia patológica.

BACKGROUND AND OBJECTIVE: Abdominal pain and diarrhoea are common symptoms in the general population. The colonoscopy is the gold standard method of detecting an organic pathology in the colon. However, it is invasive; it can not be repeated frecuently; it is expensive; and the system is overloaded. Fecal calprotectin (FCP) is a marker that may detect organic pathologies of the colon. The aims of this study were to analyze the usefulness of FCP to predict an abnormal colonoscopy and to correlate the levels of FCP with the degree of activity in inflammatory bowel disease (IBD). PATIENTS AND METHOD: 190 people were included in the study. All of them underwent a colonoscopy and a stool sample. People were divided in: normal colonoscopy: 117 people, and 28 colon adenomas, 20 colorectal cancer (CRC) and 25 IBD. RESULTS: The mean (SD) FCP concentration was 2,171.1 (2,133.6) mg/kgin patients with IBD and 726.6 mg/kg (533) in CRC. Both results were significantly elevated compared with those of healthy controls [114 (113)] mg/kg In patients with IBD, their levels correlated directly with the activity of the inflammation. 217 mg/kg was the best cut-off for discriminating patients with organic colon disorders. The sensibility was 85% and NPV was 93%. NSAIDs use was a clinical variable which was connected with a high FCP concentration in patients with normal colonoscopy. CONCLUSIONS: The higher levels of FCP were found in people with IBD and CRC. The measurement of FCP is a non-invasive, inexpensive, reliable and easily measured test. Among people with abdominal pain and diarrhoea, testing for FCP allows us to select those who must undergo a colonoscopy. NSAIDs can raise the levels of FCP in people with normal colonoscopies.