Incidence of inflammatory bowel disease in the Nord-Pas-de-Calais region and the Somme area of France in 1988

No epidemiological data on inflammatory bowel disease (IBD) are available in France. We therefore conducted a prospective epidemiologic study of IBD in the Nord-Pas de Calais region and the Somme department of France (4.5 million inhabitants). Each suspected new case was reported by all (private and public) gastroenterologists (n = 120) and a questionnaire was filled out at the gastroenterologist office by an epidemiologist. The final diagnosis of Crohn's disease (CD), ulcerative colitis (UC), or proctitis (UP) was made in a blind manner by two gastroenterologists. During 1988, 576 IBD patients were identified; 281 (49 percent) had CD, 207 (36 percent) had UC including 75 UP; and 88 (15 percent) had unclassified colitis. The incidence rate per 10(5) was 6.3 for CD and 4.6 for UC. The female/male ratio was 1.4 for CD and 0.9 for UC. The mean age at the time of diagnosis was 31 years for CD and 40.5 years for UC. The mean time between onset of symptoms and diagnosis was longer for CD (15 months) than for UC (6.8 months). These preliminary data suggest that the incidence of IBD is high in Northwestern France and comparable, for CD, to the highest incidence of Northern Europe.     

Cost of outpatient care in patients with inflammatory bowel disease in a German University Hospital

BACKGROUND AND AIM: Because of its long duration, inflammatory bowel disease (IBD) causes high use of health services and high lifetime costs for medical care. The aim of the present study was to measure the costs of outpatient care in patients with IBD in a German University Hospital and to identify potentially relevant determinants of costs. METHODS: The use of resources of 599 outpatient patients treated at a German University Hospital (65% Crohn's disease [CD] and 26% ulcerative colitis [UC]) was measured using a routine database. Costs of medical services (diagnostics and treatment) were considered as well as costs of medication. Resource use was valued using fee schedules for hospital services and pharmacy prices for drugs. RESULTS: The mean cost of one outpatient visit was Euros 162, including physician costs, laboratory costs, and costs of diagnostic procedures following the visit. For a subgroup of 272 patients, the mean annual cost for outpatient care was Euros 3171. Medication accounted for 85% of the total annual costs. Potential determinants, such as main diagnosis (CD or UC), sex, age, localization of disease, and occurrence of anemia, had no influence on costs, whereas complications of IBD and use of corticosteroids showed an impact on annual costs. CONCLUSIONS: This is the first time that the structure and range of outpatient treatment costs for IBD have been demonstrated for a German hospital.     

Specificities of the fecal microbiota in inflammatory bowel disease

BACKGROUND: Abnormalities have been described in the fecal microbiota of patients with IBD, but it is not known whether they are specific for inflammatory bowel disease (IBD) or to some extent common to other forms of colitis. The aim of this study was to compare the bacterial composition of the dominant fecal microbiota in patients with Crohn's disease (CD), ulcerative colitis (UC), infectious colitis (IC), and in healthy subjects (HS). METHODS: Fluorescent in situ hybridization adapted to flow cytometry was used to analyze the bacterial composition of fecal samples from 13 patients with active CD, 13 patients with active UC, 5 patients with IC, and 13 HS. We used 6 group-specific probes targeting 16S rRNA and spanning the main phylogenetic groups of the fecal microbiota. RESULTS: A significantly higher proportion of the total fecal bacteria were recognized by the 6 probes in HS (86.6%+/-12.7) and in IC (84.0%+/-11.7) than in patients with IBD (70.9%+/-15 in CD and 60.1%+/-25.7 in UC). The Clostridium coccoides group was reduced in UC (20.0%+/-13.3 versus 42.0%+/-12.0 in HS; P<.001), whereas the C leptum group was reduced in CD (13.1%+/-11.9 versus 25.2%+/-14.2 in HS; P=.002). The Bacteroides group was more abundant in IC (36.4%+/-22.9) than in the other 3 groups (13.8%+/-11.8 in CD, 11.7%+/-11.7 in UC, 12.1%+/-7.0 in HS; P<.001 for all 3 comparisons). CONCLUSIONS: In IBD the dominant fecal microbiota comprises unusual bacterial species. Moreover, CD and UC fecal microbiota harbor specific discrepancies and differ from that of IC and healthy subjects.     

Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation

OBJECTIVE: Lactoferrin is a glycoprotein expressed by activated neutrophils. The aim of this study was to determine the sensitivity and specificity of fecal lactoferrin concentrations for inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) versus healthy controls. METHODS: Fresh stool samples were collected from outpatients with ulcerative colitis (UC), Crohn's disease (CD), or IBS. Clinical disease activity for IBD was assessed using a modified Harvey-Bradshaw Activity Index. Fecal lactoferrin concentrations were determined using a polyclonal antibody-based enzyme linked immunoassay. Mean fecal lactoferrin concentrations for each group and sensitivity and specificity of the assay were determined. RESULTS: One hundred-four CD patients, 80 UC patients, 31 IBS patients, and 56 healthy controls were recruited. The mean +/- SE fecal lactoferrin concentration (microg/g fecal weight) was 440 +/- 128 for CD patients, 1125 +/- 498 for UC patients, 1.27 +/- 0.29 for IBS patients, and 1.45 +/- 0.4 for healthy controls. Fecal lactoferrin was 90% specific for identifying inflammation in patients with active IBD. Elevated fecal lactoferrin was 100% specific in ruling out IBS. CONCLUSIONS: Fecal lactoferrin is sensitive and specific for detecting inflammation in chronic IBD. This noninvasive test may prove useful in screening for inflammation in patients presenting with abdominal pain and diarrhea.     

Epidemiological characteristics of inflammatory bowel disease in North-Eastern Poland

AIM: To provide the clinical and epidemiological data of inflammatory bowel disease (IBD) patients of North-Eastern Poland. METHODS: A total of 248 IBD patients diagnosed and hospitalized in the Department of Infectious Diseases in Bialystok between 1990 and 2003 were included in the study. We analyzed age, sex, education, characteristics of job, type of the environment, discontinuation of employment due to IBD, colitis extent, need of surgical treatment, and coexistence of other diseases. RESULTS: Two hundred and thirty-three IBD patients (94%) were diagnosed as ulcerative colitis (DC), and only 15 (6%) were diagnosed as Crohn's disease (CD). Patients with CD were significantly younger at the time of diagnosis and male predominance was observed. The mean age of the patients at the time UC diagnosis was 44.9±1.1 years. Histogram of the age of patients showed the characteristic biphasic distribution with two peaks between 20 and 40 years and between 60 and 70 years. The predominant form of UC was left sided colitis, which affected almost 80% of the studied population. The most extensive form - pancolitis was present in 34 patients (15%). Only 6% of UC patients required surgery, whereas 36% of CD patients underwent surgery (P<0.005). Among coexisting disorders, cholelithiasis was the most prevalent and demonstrated in 35 patients (14%), pulmonary disorders were diagnosed in 2%, and psoriasis in 1.4%. Since 1998, the number of admitted IBD patients has slightly increased. CONCLUSION: Occurrence of UC in Poland is much higher than that of CD. The majority of UC cases are diagnosed in young people (20-40 years) with the predominance of male patients. The most common clinical form of UC is left sided colitis.     

Dipeptidyl peptidase IV (DP IV, CD26) in patients with inflammatory bowel disease

BACKGROUND: Dipeptidyl peptidase IV (DP IV, CD26), a serine protease with broad tissue distribution and known activity in serum, participates in T cell activation and promotes a Th1 cytokine response, a function in part attributable to its enzymatic activity. We hypothesized that the activity of DP IV in serum and expression of CD26/DP IV in lymphocytes may be altered in patients with inflammatory bowel disease (IBD). METHODS: Serum DP IV activity and CD26 (DP IV)-positive peripheral blood lymphocytes were measured in 110 patients with IBD (Crohn disease (CD): n = 63, ulcerative colitis (UC): n = 47). Additionally, T cell activation antigens (CD25, CD95) and costimulatory molecules (CD28) were evaluated. The same analyses were carried out in healthy volunteers (HC, n = 28). Thirty-nine patients with CD and 28 patients with UC were reassessed 3-6 months after the first visit. RESULTS: In patients with IBD, the DP IV activity in serum was reduced (mean +/- s (standard deviation): 52.8 U/l +/- 16.9 (CD) and 55.7 +/- 15.1 U/l (UC) versus 71.9 +/- 18.4 (HC), P < 0.001). Furthermore, patients with IBD had higher numbers of CD26-positive cells coexpressing CD25 and a higher surface expression of CD26 (DP IV) (mean fluorescence intensity, mean 57.1 (CD) and 59.8 (UC) versus 29.9 (HC), P < 0.001). The DP IV activity in serum showed an inverse correlation with known disease activity scores as well as with the concentrations of orosomucoid in serum. CONCLUSION: The changes of DP IV in patients with IBD highlight alterations at an interface between immune function and metabolism of peptide hormones, with potential importance for the pathophysiology of IBD. Furthermore, these changes may help to refine the assessment of IBD activity.     

Clinical epidemiology of inflammatory bowel disease in Lebanon

BACKGROUND: The objectives of this study were to determine the prevalence and incidence of inflammatory bowel disease (IBD) in a representative Lebanese cohort and to describe practice prevalence trends, disease characteristics, and impact on quality of life (QoL) of IBD patients in Lebanon. METHODS: All of a university-based health program's 2000-2004 computerized records that listed a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were reviewed. In addition, data on patients seen in the gastroenterology clinics and data from the IBD registry at the American University of Beirut Medical Center (AUBMC) from the same period were analyzed. RESULTS: Of 15,073 insured individuals, 8 had a diagnosis of CD and 16 of UC, giving an age-adjusted prevalence of 53.1 per 100,000 people for CD and 106.2 per 100,000 people for UC. The mean age at diagnosis for patients with CD and UC was 28.8 +/- 11.1 and 32.0 +/- 13.4 years, respectively, and there was a slight female predominance. The mean annual incidence was 4.1 per 100,000 people for UC and 1.4 per 100,000 people for CD (range, 0-6.9/100,000 for both). Of the 10,383 patients seen in the gastroenterology clinic from 2000 to 2004, 251 (2.4%) had IBD (142 UC, 100 CD, and 9 indeterminate), a ratio that trended upward over time (range, 1.8%-2.7%). The median IBD Quality-of-Life (IBDQ) questionnaire score was 124.9 +/- 30.5, indicating that the disease had a moderately severe impact on QoL. CONCLUSIONS: The prevalence of IBD in this representative Lebanese cohort falls in the intermediate range of that reported for white populations in Europe and North America. Future studies are needed to examine local risk factors, disease genotypes and phenotypes, and epidemiologic time trends. The psychosocial burden of IBD in Lebanon appears significant.     

Loss of fragile histidine triad protein expression in inflammatory bowel disease

INTRODUCTION Inflammatory bowel disease (IBD) is a collection of chronic idiopathic in? ammatory disorders of the intestine and/or colon, including two independent diseases: ulcerative colitis (UC) and Crohn’s disease (CD)[1]. Up to now, the complex etio…     

Epidemiology of chronic inflammatory bowel disease in the Northern area of Huelva.

OBJECTIVE: To know the different epidemiologic aspects of chronic inflammatory bowel disease (IBD) in the Northern area of the province of Huelva. MATERIAL AND METHODS: we carried out a retrospective (1980-1996) and prospective (1996-2003) study of all patients diagnosed with IBD in the Northern area of Huelva, with 77,856 inhabitants. The distribution of Crohn s disease (CD) and ulcerative colitis (UC) was analyzed, as well as sex, age and smoking habit at the time of diagnosis, familial aggregation, appendicectomy rate, phenotype (anatomical site and clinical types), extraintestinal manifestations, and immunosuppressive therapy or surgical requirements. RESULTS: 70 patients with IBD were studied, 40 with UC and 30 with CD. Sex distribution was 39 (55.7%) males (55% with CD vs 56.6% with UC; NS) and 31 (44.3%) females (45% with CD vs 43.3% with UC; NS). Mean age at presentation was 44.7 +/- 19.32 years in UC vs 32.3 +/- 16.43 in CD; p < 0.001. Familial association was 7.1%. Previous appendicectomy was referred in 2.5% of patients with UC vs 36.7% of those with CD (p < 0.001), and the percentage of smokers was also higher in CD 66.7% vs CU 12.5% (p < 0.001). Anatomical site in UC was: proctitis, 20%; proctosigmoiditis/left colon, 42.5%; extensive colitis, 25%; and pancolitis, 12.5%; in CD was: terminal ileum, 43.3%; colon, 20%; and ileo-colon, 36.7%. The disease patterns were: inflammatory 56.7%, obstruction 26.7%, and fistulization 16.7%. Extraintestinal manifestations were diagnosed in 7.5% of patients with UC vs 16.6% patients with CD; surgery was performed in one patient with UC vs 10 with CD, and one patient with UC required immunosuppressive treatment vs 12 with CD. A multivariant analysis showed that younger age and smoking habit were risk factors for CD vs advanced age in UC, in which case, the smoking habit was a protective factor. The mean incidence rate of IBD starting from 1996 and expressed in cases/100,000 inhabitants/year was 5.2 for UC and 6.6 for CD. CONCLUSIONS: The mean incidence of UC in our area was 5.2 cases/100,000/inhabitants/year, and 6.6 for CD. Patients presenting with CD are diagnosed at a significantly younger age that those with UC; the smoking habit is a risk factor for CD while it protects from UC. The characteristics of IBD in our geographical area do not differ substantially from those in other regions of Spain.     

Increasing incidences of inflammatory bowel disease and decreasing surgery rates in Copenhagen City and County, 2003-2005: a population-based study from the Danish Crohn colitis database

OBJECTIVES: A continuous increase in the incidence of inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC) has been suggested. Since Denmark provides excellent conditions for epidemiological research, we aimed to describe contemporary IBD incidence rates and patient characteristics in Copenhagen County and City. METHODS: All patients diagnosed with IBD during 2003-2005 were followed prospectively. Demographic and clinical characteristics, such as disease extent, extraintestinal manifestations, smoking habits, medical treatment, surgical interventions, cancer, and death, were registered. RESULTS: Five-hundred sixty-two patients were diagnosed with IBD, resulting in mean annual incidences of 8.6/10(5) for CD, 13.4/10(5) for UC, and 1.1/10(5) for IC. Time from onset to diagnosis was 8.3 months in CD and 4.5 months in UC patients. A family history of IBD, smoking, and extraintestinal manifestations was significantly more common in CD than in UC patients. Only 0.6% of UC patients had primary sclerosing cholangitis. In CD, old age at diagnosis was related to pure colonic disease, whereas children significantly more often had proximal and extensive involvement. Twelve percent of CD patients and 6% of UC patients underwent surgery during the year of diagnosis, significantly less than earlier reported. CONCLUSIONS: The incidence of IBD in Copenhagen increased noticeably during the last decades. Time from onset of symptoms until diagnosis decreased markedly, extent of CD was related to age at diagnosis, and the risk of surgery was low in UC.     

Inflammatory bowel disease in Iran: a review of 457 cases

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) was believed to be infrequent in Iran; however, unofficial reports have confessed the continuing rise in IBD in our country. METHODS: Demographic and clinical features, extraintestinal manifestations, extension of disease and complications of 401 patients with ulcerative colitis (UC), 47 with Crohn's disease (CD), and nine with indeterminatn colitis (IC) were assessed retrospectively. The exact course of physicians' visits of 250 IBD patient was asked through face-to-face interview. RESULTS: Mean age at diagnosis was 31.9 years in UC and 30.5 years in CD patients. The male to female ratio was 0.8 for UC and 1.3 for CD. The percentage of CD and UC patients who were non-smokers was 82.9 and 84.5%, respectively. Patients with UC presented with rectal bleeding (41.9%), whereas those with CD complained of abdominal pain (46.9%). Among UC patients, proctosigmoid was affected in 51.9%. Colorectal cancer was diagnosed in two patients. The mean lag time between the onset of symptoms and definite diagnosis was 13.9 and 17.7 months for UC and CD patients, respectively. A total of 32.4% of patients with IBD had at least one of the five major extra-intestinal diseases. Conclusion: The demographic and clinical picture of IBD is more or less the same as that of other developing countries; however, the rarity of CD in Iran is noted. Although the true epidemiologic profile of IBD in Iran is still unknown, it is not as rare as previously thought, and it seems as if gradual adoption of a Western lifestyle may be associated with the continuing rise in IBD.     

Indeterminate colitis: a significant subgroup of pediatric IBD

BACKGROUND: Indeterminate colitis (IC) is a subgroup of inflammatory bowel disease (IBD) that cannot be characterized as either ulcerative colitis (UC) or Crohn's disease (CD). Our aims are to determine the prevalence of IC in our pediatric patient population and to describe its clinical presentation, natural history,and disease distribution. METHODS: We performed a retrospective database analysis of all children diagnosed with IBD at the Johns Hopkins Children's IBD Center between 1996 and 2001. Patient demographics, including age, sex, and age at disease onset, were tallied. Disease distribution was identified on the basis of a review of all endoscopic, colonoscopic, histopathological, and radiological records. All of the patients were followed up clinically to determine the extent of disease progression on the basis of the initial diagnosis of IC. RESULTS: Among 250 children registered in the database, 127 (50.8%) had a diagnosis of CD, 49 (19.6%) had UC, and 74(29.6%) had IC. Patients with IC had a significantly younger mean +/- SEM age (9.53 +/- 4.8 years) at diagnosis compared with patients with CD (12.4 +/- 3.8 years; P < 0.001) but not compared with patients with UC (7.41 +/- 3.5 years). Among the patients with IC, 59 (79.7%) had a pancolitis at diagnosis, and the remaining 15 had left-sided disease that progressed to a pancolitis within a mean of 6 years. Twenty-five patients (33.7%) with an initial diagnosis of IC were reclassified to either CD or UC after a median follow-up of 1.9 years (range 0.6-4.5 years). Forty-nine patients (66.2%) maintained their diagnosis of IC after a mean follow-up of 7 years (SEM 2.5 years). CONCLUSIONS: IC is a distinct pediatric subgroup of IBD with a prevalence that is higher than that observed in adults. Children with IC have an early age of disease onset and a disease that rapidly progresses to pancolitis. Longitudinal studies are needed to determine the clinical implications of this pediatric IBD subgroup.     

Fibromyalgia in inflammatory bowel disease.

OBJECTIVE: Studies of the rheumatological complications of inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) have focused on peripheral arthritis and spondylitis, and less is known about soft tissue rheumatism, specifically the fibromyalgia syndrome (FM). Our aim was to estimate the prevalence of FM and assess pain thresholds in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Seventy-two patients with UC and 41 with CD attending consecutively at the Gastroenterology Outpatient Clinic were assessed for the presence of FM and tenderness thresholds. FM was diagnosed according to the American College of Rheumatology 1990 criteria. Tenderness was measured by manual palpation and with a dolorimeter. One hundred twenty healthy subjects served as controls. RESULTS: FM was documented in 30 of 113 patients with IBD (30%), specifically in 49% of patients with CD and 19% with UC (p = 0.001); in controls the rate was 0%. Subjects with CD exhibited more tenderness and reported more frequent and more severe FM associated symptoms than subjects with UC. Patients with CD had a higher tender point count, 11.3 (+/- 6.5), than those with UC, 6.4 (+/- 5.7) (p = 0.001); in healthy controls, the count was 0.1 (+/- 0.5). Tenderness thresholds (kg) were lower in CD 2.9 (+/- 1.7) than UC 3.9 (+/- 2.0) (p = 0.005) and controls 5.8 (+/- 0.9). CONCLUSION: FM is common in IBD, particularly Crohn's disease. The lower pain threshold in Crohn's disease may suggest a disease-specific effect. Recognizing FM in patients with IBD will prevent misdiagnosis and ensure correct treatment.     

Change of diagnosis during the first five years after onset of inflammatory bowel disease: results of a prospective follow-up study (the IBSEN Study)

OBJECTIVE: An exact diagnosis of inflammatory bowel disease (IBD) and further subclassification may be difficult even after clinical, radiological and histological examinations. A correct subclassification is important for the success of both medical and surgical therapeutic strategies, but there is a dearth of information available on the frequency of changes in diagnosis in population-based studies. The objective of this work was prospectively to re-evaluate the diagnosis in an unselected cohort of IBD patients during the first five years after the initial diagnosis. MATERIAL AND METHODS: Patients classified as IBD or possible IBD in the period 1990-94 (the IBSEN cohort) had their diagnosis re-evaluated after 1 and 5 years. Initially, the patients were classified as ulcerative colitis (UC), Crohn's disease (CD), indeterminate colitis (IC) or possible IBD. At the 5-year visit, patients were classified as UC, CD or non-IBD. RESULTS: A total of 843 patients (518 UC, 221 CD, 40 IC and 64 possible IBD) were identified. Clinical information was available for 94% of the patients who survived after 5 years. A change in diagnosis was found in 9% of the patients initially classified as UC or CD. A change to non-IBD was more frequent than a change between UC and CD. A large proportion of patients initially classified as IC or possible IBD were diagnosed as non-IBD after 5 years (22.5% versus 50%). When IBD was confirmed in these groups, UC was more frequent than CD. Two changes in diagnosis during follow-up were observed in 2.8% of the patients; this was more frequent in patients initially classified as IC or possible IBD. CONCLUSIONS: There are obvious diagnostic problems in a minority of patients with IBD; a systematic follow-up is therefore important in these patients.     

Serum lipopolysaccharide-binding protein in endotoxemic patients with inflammatory bowel disease

BACKGROUND: In inflammatory bowel disease (IBD), enhanced inflammatory activity in the gut is thought to increase the risk of bacterial translocation and endotoxemia. By searching for signs of endotoxin-signaling cascade activation, including augmented levels of endotoxin, lipopolysaccharide-binding protein (LBP), and soluble CD14 receptor (sCD14), this prospective study sought to establish whether endotoxemia could contribute to greater clinical activity of disease. METHODS: Concentrations of plasma endotoxin, LBP, sCD14, several cytokines, acute phase proteins and clinical activity indices were determined in 104 patients with Crohn's disease (CD) and 52 patients with ulcerative colitis (UC). RESULTS: Endotoxemia was present in 48% of the patients with CD and in 28% of the patients with UC. The mean LBP was higher in patients with active CD (23.1 +/- 13.7 microg/mL) and UC (21.4 +/- 10.9 microg/mL) than in healthy controls (7.2 +/- 1.8 microg/mL; P < 0.01). Elevated serum concentrations of endotoxin and LBP were even detected in patients with inactive CD. Among the patients with active IBD, those with higher endotoxin levels had the worst clinical activity scores and the highest LBP levels. Treatment normalized LBP concentrations, from 29.1 +/- 13.0 to 15.2 +/- 7.3 microg/mL; (P < 0.05) in active CD and from 21.7 +/- 9.8 to 13.6 +/- 5.7 microg/mL; (P < 0.01) in active UC, along with normalizing endotoxin and sCD14 plasma concentrations. CONCLUSIONS: Patients with IBD show increased serum levels of endotoxin, LBP and sCD14. This alteration correlates with disease activity, with normal levels recovered after treatment, although less completely in Crohn's disease, and parallels a rise in proinflammatory cytokines, suggesting a contribution of bacterial products to the inflammatory cascade in these patients.     

Tacrolimus is safe and effective in patients with severe steroid-refractory or steroid-dependent inflammatory bowel disease--a long-term follow-up

OBJECTIVE: We and others have reported the use of tacrolimus in refractory inflammatory bowel disease (IBD). Little is known about its long-term efficacy and safety. METHODS: In this retrospective, observational single center study the charts of 53 adult patients with steroid-dependent (n = 18) or steroid-refractory (n = 35) IBD, Crohn's disease (CD) (n = 11), ulcerative colitis (UC) (n = 40), or pouchitis (PC) (n = 2) were reviewed. Tacrolimus (0.1 mg/kg body weight per day) was administered orally in all and initially intravenously in 2 patients (0.01 mg/kg body weight per day), aiming for serum trough levels of 4-8 ng/mL. Forty-one of 53 (77.1%) patients were receiving concomitant azathioprine. The mean treatment duration was 25.2 +/- 4.6 SD months (0.43-164 months). Patients were followed for a mean of 39 +/- 4.1 SD months (5-164 months). Response was evaluated using a modified clinical activity index (M-CAI). RESULTS: Thirty-one UC (78%), 10 CD (90.1%), and both PC (100%) patients experienced an immediate clinical response or went into remission at 30 days. A statistically significant drop on the M-CAI was documented for UC and CD patients. Nine UC patients (22.5%) underwent colectomy between 1.6 and 41.3 months following initiation. Mean colectomy-free survival was 104.8 +/- 15.5 (95% CI 74.4-135.2) months (limited to 164.4 months). Cumulative colectomy-free survival was estimated 56.5% at 43.8 months. Steroids were reduced or discontinued in 40 of 45 UC and CD patients (90%) taking steroids. Side effects included a temporary rise of creatinine (n = 4, 7.6%), tremor or paresthesias (n = 5, 9.4%), hyperkalemia (n = 1, 1.9%), hypertension (n = 1, 1.9%), and opportunistic infections (n = 2, 3.8%). CONCLUSION: Long-term tacrolimus therapy appears safe and effective in refractory IBD.     

Real-world treatment patterns and disease control over one year in patients with inflammatory bowel disease in Brazil

BACKGROUNDCrohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) with a remission-relapsing presentation and symptomatic exacerbations that have detrimental impacts on patient quality of life and are associated with a high cost burden, especially in patients with moderate-to-severe disease. The Real-world Data of Moderate-to-Severe Inflammatory Bowel Disease in Brazil (RISE BR) study was a noninterventional study designed to evaluate disease control, treatment patterns, disease burden and health-related quality of life in patients with moderate-to-severe active IBD. We report findings from the prospective follow-up phase of the RISE BR study in patients with active UC or CD.AIMTo describe the 12-mo disease evolution and treatment patterns among patients with active moderate-to-severe IBD in Brazil.METHODSThis was a prospective, noninterventional study of adult patients with active Crohn’s disease (CD: Harvey-Bradshaw Index ≥ 8, CD Activity Index ≥ 220), inadequate CD control (i.e., calprotectin > 200 µg/g or colonoscopy previous results), or active ulcerative colitis (UC: Partial Mayo score ≥ 5). Enrollment occurred in 14 centers from October 2016 to February 2017. The proportion of active IBD patients after 9-12 mo of follow-up, Kaplan-Meier estimates of the time to mild or no activity and a summary of treatment initiation, discontinuation and dose changes were examined.RESULTSThe study included 118 CD and 36 UC patients, with mean ± SD ages of 43.3 ± 12.6 and 44.9 ± 16.5 years, respectively. The most frequent drug classes at index were biologics for CD (62.7%) and 5-aminosalicylate derivates for UC patients (91.7%). During follow-up, 65.3% of CD and 86.1% of UC patients initiated a new treatment at least once. Discontinuations/dose changes occurred in 68.1% of CD patients [median 2.0 (IQR: 2-5)] and 94.3% of UC patients [median 4.0 (IQR: 3-7)]. On average, CD and UC patients had 4.4 ± 2.6 and 5.0 ± 3.3 outpatient visits, respectively. The median time to first mild or no activity was 319 (IQR: 239-358) d for CD and 320 (IQR: 288-358) d for UC patients. At 9-12 mo, 22.0% of CD and 20.0% of UC patients had active disease.CONCLUSIONAlthough a marked proportion of active IBD patients achieved disease control within one year, the considerable time to achieve this outcome represents an unmet medical need of the current standard of care in a Brazilian real-world setting.     

Elevated thrombopoietin serum levels in patients with inflammatory bowel disease

OBJECTIVES: Elevated platelet count is a well recognized marker of inflammatory bowel disease (IBD) activity. Thrombopoietin (TPO) is a critical cytokine in the physiological regulation of thrombopoiesis. The aim of this study was to investigate the serum levels of endogenous TPO in patients with IBD, the relationship between platelet counts and TPO levels, and the correlation of TPO with the clinical characteristics of the patients. METHODS: TPO levels in 40 patients with Crohn's disease (CD), 63 patients with ulcerative colitis (UC), and in 42 healthy blood donors were assessed by ELISA. Platelet and white blood cell counts as well as C-reactive protein, and erythrocyte sedimentation rate were measured. RESULTS: TPO levels were significantly elevated in patients with CD (mean 124.3 +/- SD 58.0 pg/ml, p < 0.0001) and in patients with UC (mean 152.2 +/- SD 142.3 pg/ml, p < 0.0001), compared to controls (mean 53.4 +/- SD 45.7 pg/ml). TPO levels remained significantly elevated in remission (mean 144.7 +/- SD 131.1 pg/ml, p < 0.0001 compared to controls). Platelets were significantly elevated only in active CD, being normal in inactive disease as well as in all patients with UC. There was no significant correlation between TPO levels and various clinical characteristics of patients with IBD. No significant correlation was found between TPO levels and either platelet counts or white blood cell counts, erythrocyte sedimentation rate, and C-reactive protein. CONCLUSIONS: TPO levels are increased in IBD, irrespective of disease activity, platelet counts, and clinical characteristics of the patients. These observations indicate that TPO, apart from being a platelet producer, might have additional functions, probably related to the procoagulant state of IBD.     

Plasma thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 levels in inflammatory bowel disease

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an increased risk of thromboembolic events. Imbalance of fibrinolysis has been suggested as one of the possible pathogenetic mechanisms. As plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) are inhibitors of fibrinolysis, we studied TAFI as well as PAI-1 plasma levels in IBD patients compared with healthy controls. METHODS: A total of 132 IBD patients [68 ulcerative colitis (UC) and 64 Crohn's disease (CD)] and 50 healthy controls were enrolled. PAI-1 and TAFI plasma levels were assessed by commercially available enzyme-linked immunosorbent assay kits. Their relationship with clinical parameters of UC and CD was assessed. RESULTS: Mean plasma PAI-1 levels were significantly higher in both UC patients (3.9+/-1.3 IU/ml) and CD patients (4.0+/-1.5 IU/ml) compared with healthy controls (3.1+/-1.1 IU/ml) (P=0.01). On the other hand, mean plasma TAFI levels were significantly lower in both UC patients (14.7+/-3.1 microg/ml) and CD patients (13.3+/-3.4 microg/ml) compared with healthy controls (17.4+/-3.0 microg/ml) (P<0.0001). Patients with active disease had significantly higher PAI-1 levels compared with patients with inactive disease for both diseases (P=0.03 and P=0.01, respectively). No significant association between plasma TAFI levels and disease activity was also found. Plasma TAFI levels were significantly lower in patients with ileal CD compared with patients with colonic CD. CONCLUSION: PAI-1 plasma levels are increased whereas TAFI levels are decreased in IBD patients. These results suggest an imbalance of fibrinolysis in IBD.