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R A van Hogezand

Publications and source records attributed to R A van Hogezand.

At least 19 recordsLinked to original sources
PubMed2006

Ileum resection is the most predictive factor for osteoporosis in patients with Crohn's disease.

INTRODUCTION: Crohn's disease is associated with a host of factors potentially increasing the risk for osteoporosis and fractures. The aim of our study was to identify the most predictive factors for skeletal pathology in this patients. METHODS: Using a cross-sectional study design, 146 randomly selected patients with Crohn's disease of variable disease activity who were given standard therapy to control disease activity, including glucocorticoids, and who attended the outpatient clinic of the Gastroenterology Unit on regular follow-up visits were studied. Bone mineral density (BMD) measurements and lateral X-rays of the spine were performed, and biochemical parameters of bone turnover, gonadal hormones and C-reactive protein (CRP) as markers of disease activity were measured in all patients. RESULTS: There were 61 men and 85 women, with a mean age of 43 years and mean disease duration of 20 years. The majority of patients (86%) had been treated with glucocorticoids at some stage during their illness at a median dose of 7.5 mg/day, 43% were currently using these agents and 66% had undergone an intestinal resection. Twenty-one percent of patients had below-normal 25-hydroxy vitamin D levels. Osteoporosis was documented in 26% of patients, predominantly at the femoral neck, but also at the lumbar spine or at both sites; osteopenia was documented in 45% of patients. Prevalence of vertebral and non-vertebral fractures was, respectively, 6% and 12%. Ileum resection was the most predictive factor for osteoporosis: RR 3.84 (CI 1.24-9.77, p=0.018), followed by age: RR 1.05 (CI 1.02-1.08, p<0.001) and current or past glucocorticoid use: RR 1.94 (CI 0.92-4.10, p=0.08). CONCLUSION: Our data suggest that in patients with Crohn's disease, the risk of osteoporosis is best predicted by a history of ileum resection.

Adolescent↗
PubMed2006

Skeletal morbidity in inflammatory bowel disease.

Patients with Crohn's disease are at increased risk of developing disturbances in bone and mineral metabolism because of several factors, including the cytokine-mediated nature of the inflammatory bowel disease, the intestinal malabsorption resulting from disease activity or from extensive intestinal resection and the use of glucucorticoids to control disease activity. Inability to achieve peak bone mass when the disease starts in childhood, malnutrition, immobilization, low BMI, smoking and hypogonadism may also play a contributing role in the pathogenesis of bone loss. The relationship between long-term use of glucocorticoids for any disease indication and increased risk for osteoporosis and fractures is well established. However, the relationship between Crohn's disease and ulcerative colitis and bone loss remains controversial. Depending on the population studied the prevalence of osteoporosis has thus been variably reported to range from 12 to 42% in patients with inflammatory bowel disease (IBD). In IBD most studies demonstrate a negative correlation between bone mineral density (BMD) and glucocorticoid use, but not all authors agree on the relationship between long-term glucocorticoid use and continuing bone loss. Whereas prospective studies do suggest sustained bone loss at both trabecular and cortical sites in long-term glucocorticoid users with inflammatory bowel disease, a decrease in bone mass is also observed in patients with active Crohn's disease not using glucocorticoids, and bone loss is not universally observed in patients with Crohn's disease using orally or rectally administered glucocorticoids. Data on vertebral fractures are scarce and there is no agreement about the risk of non-vertebral fractures in patients with Crohn's disease, although it has been suggested that non-vertebral fracture risk may be increased by up to 60% in patients with IBD. A recent publication reports an increased risk of hip fractures in Crohn's disease related to current and cumulative corticosteroid use and use of opiates, although these fractures could not be related to the severity of osteoporosis. The issue of the magnitude of the problem of osteoporosis has become particularly relevant in Crohn's disease, since the ability of therapeutic interventions to beneficially influence skeletal morbidity has been clearly established in patients with osteoporosis, whether post-menopausal women, men or glucocorticoid users. The main question that arises is whether all patients with Crohn's disease should be treated with bone protective agents on the assumption that they all have the potential to develop osteoporosis or whether the use of these agents should be restricted to patients clearly at risk of osteoporosis and fractures, providing these can be identified. We recommend, based on the available literature and our own experience, that all patients with Crohn's disease should be screened for osteoporosis by means of a bone mineral density measurement in addition to full correction of any potential calcium and vitamin D deficiency, to allow timely therapeutic intervention of the patient at risk while sparing the vast majority unnecessary medical treatment.

Bone Density↗
PubMed2005

Expression of matrix metalloproteinases-2 and -9 in intestinal tissue of patients with inflammatory bowel diseases.

BACKGROUND/AIMS: Matrix metalloproteinases are major contributors in the breakdown and reconstitution of basement membranes and extracellular matrix in pathophysiological processes. We assessed the expression of matrix metalloproteinases-2 and -9 in intestinal tissue of patients with inflammatory bowel disease. PATIENTS/METHODS: Resected tissue specimens from patients with Crohn's disease or ulcerative colitis and control tissue from patients with a colorectal carcinoma were used for enzyme-linked immunosorbent assay, zymography, activity assay, reverse transcription polymerase chain reaction and immunohistochemistry to evaluate the expression of these matrix metalloproteinases. RESULTS: Matrix metalloproteinase-2 and more strongly matrix metalloproteinase-9 protein and mRNA were markedly increased in inflammatory bowel disease tissues, with the highest levels in severely inflamed tissues. Immunohistochemistry showed that matrix metalloproteinase-2 was present in the extracellular matrix of the submucosa, with a lower but more generalised expression in the severely inflamed regions. Matrix metalloproteinase-9 was most prominent in polymorphonuclear leukocytes and was increased, also in activity, in all inflammatory bowel disease tissues. An increased matrix metalloproteinase-9 expression in the extracellular matrix was observed in relation to the severity of inflammation. CONCLUSIONS: Matrix metalloproteinases-2 and -9 are enhanced in the intestinal tissue and seem to be actively involved in the inflammatory and remodelling processes in inflammatory bowel disease, without major differences between CD and UC.

Adult↗
PubMed2002

Effects of anti-tumour necrosis factor-alpha therapy on the quality of life in Crohn's disease.

BACKGROUND: Infusion of anti-tumour necrosis factor-alpha appears to be highly effective in patients with Crohn's disease. AIM: To assess the effect of infliximab on the quality of life in patients with active or fistulizing disease, as measured by the inflammatory bowel disease questionnaire, and to examine the impact on its four dimensions. METHODS: An observational study was conducted in 65 patients. An infusion of 5 mg/kg infliximab was given at week 0 in patients with active disease and at week 0, 2 and 6 in fistulizing disease. Changes from baseline in the total and dimensional inflammatory bowel disease questionnaire scores were calculated and compared between the patient groups. Potential predictors of change in the quality of life were identified. RESULTS: In the active disease group, at week 4, the mean total and dimensional inflammatory bowel disease questionnaire scores improved compared to baseline (P < 0.001). In the fistulizing group, at week 6, all scores changed from baseline (P < 0.05). Improvement in the total inflammatory bowel disease questionnaire score correlated well with the improvement of the Crohn's disease activity index. Systemic and social scores improved more than bowel and emotional scores. Inflammatory Crohn's disease and a young age at diagnosis were predictors for a better response to infliximab therapy. CONCLUSIONS: Infliximab therapy improves all dimensions of the quality of life in patients with Crohn's disease.

Adult↗
PubMed2002

Malignancies in inflammatory bowel disease: fact or fiction?

BACKGROUND: The association between ulcerative colitis (UC), Crohn disease (CD) and colorectal cancer (CRC) has been confirmed in several studies. The aim of this study was critical analysis of the relation between IBD and malignancy. METHODS: Review of the literature. RESULTS: In UC, the extent of the disease, its duration and start at a young age are risk factors for the development of CRC. Primary sclerosing cholangitis and colonic strictures are additional risk factors for development of CRC. The relation between azathioprine or 6-MP and the development of lymphomas is a subject of debate. The administration of anti-TNF-alpha has produced some concern about the development of lymphomas in CD. However, at present there is no evidence of lymphomas caused by anti-TNF-alpha in CD. On the contrary, some drugs seem to have a preventive effect on CRC development in UC. 5-aminosalicylic acid in particular and to a lesser extent sulphasalazine have prevented the development of CRC significantly in retrospective studies. In CD, there is no strong relationship between the disease and the development of CRC or other malignancies. Only the development of small-bowel carcinoma is reported with a much higher frequency. CONCLUSIONS: There is a correlation with UC and the development of CRC. For CD, this correlation is less firmly established. There is a possible, but not proven, relation between AZA/6-MP use and the development of lymphoma in IBD. There is also a probable relationship between CD and the development of small-bowel carcinoma. In some retrospective studies, the use of 5-aminosalicylic or sulphasalazine has been shown to prevent the development of CRC in UC.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Adult height in patients with early onset of Crohn's disease.

BACKGROUND: Growth impairment during childhood and adolescence is a common problem faced by patients with an early onset of Crohn's disease. AIMS: To establish how the final adult height is affected in patients with early onset of symptoms of Crohn's disease. METHODS: Information on height, parental height, and disease history was obtained from 135 patients with Crohn's disease who reached their adult height (men 22-40 years, women 18-40 years) using a questionnaire and by outpatient measurement of height where possible. Subsequently, adult heights were expressed as standard deviation scores, with and without correction for the expected target height. RESULTS: Patients with onset of disease before puberty were shorter compared with patients with onset in adulthood (p<0.01). This difference was not statistically significant when adult heights were corrected for parental height. Also, height standard deviation scores for those patients with onset of disease before puberty were significantly lower than those with onset of disease during puberty (p<0.05) but after correction for parental height the difference was not significant. The site of disease had no influence on adult height. Patients who had used corticosteroids during puberty were significantly shorter than patients who had not (p=0.005). This was also true when corrected for target height (p=0.007). CONCLUSIONS: Although there was a trend indicating a deficit in adult height in patients with an early onset of Crohn's disease, once adjustment was made for parental height, this difference was not significant. Use of corticosteroids in puberty resulted in lower adult height.

Adolescent↗
PubMed2001

Use of anti-tumour necrosis factor agents in inflammatory bowel disease. European guidelines for 2001-2003.

The introduction of novel anti-tumor necrosis factor (TNF) agents has not only led to impressive new therapeutic opportunities but also resulted in uncertainty regarding their optimal use and possible side effects. Guidelines are presented here for the use of anti-TNF agents in gastrointestinal disorders. Experts were chosen from different European countries by an algorithm to avoid bias. An expert consensus on guidelines was established using a two-stage procedure of systematic Medline and abstract search for evidence and a qualifying meeting to derive recommendations. Detailed guidelines were developed for the use and the future clinical development of anti-TNF agents in inflammatory bowel disease. Grading of available evidence and grading of recommendations were performed according to AHCPR guidelines. At present infliximab is the only registered agent for Crohn's disease. Infliximab should be always used at a dose of 5 mg/kg. The guidelines define the indications both in refractory and in fistulating disease for the readministration and before surgery. Guidelines for safety and for concomitant treatments are given. Prospects, potential clinical use, and future directions for the clinical development of other anti-TNF agents are detailed. Clinical use of anti-TNF agents will be influenced by a large number of clinical trials being concluded in 2001 and 2002. It is likely that anti-TNF therapies will become an important long-term therapy for a proportion of patients with Crohn's disease. Biological agents will be followed by smaller and more stable, orally available compounds. These guidelines will be succeeded by a formal public consensus in 2002/2003.

Crohn Disease↗
PubMed2001

Ileoanal pouch function is related to postprandial pouch tone.

BACKGROUND: Functional impairments are frequently observed in patients with an ileoanal pouch. Meal ingestion increases pouch tone and motility. Little is known, however, about the influence of meal-stimulated pouch characteristics on pouch function. The aim was to characterize basal and postprandial pouch motor and sensory characteristics in relation to clinical pouch function in patients with an ileoanal pouch. METHODS: Nineteen patients with an ileoanal pouch, without faecal incontinence but with either a high stool frequency (n = 8) or an adequate stool frequency (n = 11), underwent pressure distension of the pouch, by which pouch compliance and sensitivity characteristics were assessed using an electronic barostat. A set pressure procedure was performed to assess the influence of a meal on pouch tone and motility. RESULTS: Mean(s.d.) compliance was 10(6) and 11(4) ml/mmHg in the groups with poor and adequate pouch function respectively (P not significant). Mean(s.d.) visual analogue scale scores (0-10 cm) for urge at the highest pressure of 28 mmHg were 2.3(1.0) versus 2.3(2.4) cm respectively (P not significant); those for pain were 0.8(1.0) versus 0.5(0.7) (P not significant). Postprandially mean(s.d.) pouch volume decreased by 70(24) per cent in the group with poor pouch function and 29(25) per cent in the group with adequate pouch function (P < 0.01). The frequency and amplitude of phasic pouch contractions increased significantly postprandially, but no differences in motility characteristics were observed between the two groups. CONCLUSION: In patients with uniform pouch design and follow-up after pouch construction, pouch compliance and sensitivity were no different between patients with normal and high stool frequency; however, postprandial pouch tone was increased significantly in patients with a high stool frequency.

Adenomatous Polyposis Coli↗
PubMed2001

Proximal Crohn's disease: review of the clinicopathologic features and therapy.

Crohn's disease in the proximal region of the digestive tract is uncommon. Better diagnostically procedures and more careful histologic examination has led to a higher detection of proximal Crohn's disease. The diagnosis is based on symptoms, endoscopy with serial sections, or double contrast radiography. The most common histologic finding for this diagnosis are granulomas in the mucosa in Helicobacter pylori-negative patients, but the granulomas are not always frequently detected. Endoscopic lesions in the proximal regions look like the lesions that could be found in the distal regions. Notching in the duodenal folds could be a strong indication for Crohn's desease. Radiological lesions are not always characteristic, but should be used in combination with endoscopy. Stenosis is an important complication, but fistula formation and pseudodiverticular formation is possible. There is no uniform medical therapy, but the regular anti-inflammatory management for Crohn's disease is most often used. Sometimes surgery is needed.

Crohn Disease↗
PubMed2001

Gender-related differences in the clinical course of Crohn's disease.

OBJECTIVE: The aim of this study was to analyze the clinical and epidemiological differences between women and men affected by Crohn's disease. METHODS: The clinical course of 275 female Crohn's disease patients was compared with that of 266 male patients. RESULTS: Mean age at onset of symptoms and at diagnosis was 25.7 yr versus 27.7 yr and 28.8 yr versus 30.7 yr in women and men, respectively. Mean lag-time between onset of symptoms and establishment of the diagnosis were similar in both groups, without differences in presenting symptoms and initial localization of lesions. In women, however, some extraintestinal manifestations of Crohn's disease were found to occur more often. The percentage of patients who underwent an abdominal operation was quite similar in both groups (81% vs 77%). Mean lag-time between onset of symptoms and first bowel resection was not different. However, the lag-time between bowel resection and recurrence of disease was significantly shorter in women than in men (respectively, 4.8 yr vs 6.5 yr, p = 0.04), particularly regarding primary ileocecal resections. Overall, ileocecal resections were significantly more frequently performed in female than male patients (44% and 32%, respectively, p = 0.004). Female patients were also found to have significantly more often relatives in the first or second degree affected by Crohn's disease than male patients (15% vs 8.3%, p = 0.02). CONCLUSIONS: Extraintestinal manifestations occur more often in female Crohn's disease patients than in male patients. Furthermore, an ileocecal resection, which is accompanied by an earlier recurrence, is more often performed in female than in male patients. Female patients have more often relatives with the same disease.

Adult↗
PubMed2001

How effective is extensive nonsurgical treatment of patients with clinically active Crohn's disease of the terminal ileum in preventing surgery?

BACKGROUND/AIMS: The purpose of this study is to determine the effectiveness of extensive nonsurgical management of patients with clinically active Crohn's disease of the terminal ileum and to identify parameters that could predict failure of this nonsurgical approach. METHODS: All consecutive patients hospitalized for the first time because of active Crohn's disease of the terminal ileum between 1985 and 1994 were included. Two groups of patients were defined. Patients who responded favorably to the extensive treatment protocol (group I), and patients in whom an ileocolic resection had been performed (group II). Treatment and patient characteristics were related to outcome. RESULTS: Twenty-nine (38%) of the 76 patients were treated successfully by nonsurgical management (group I) and did not have surgery until the end of follow-up (mean 8.0 years, range 3-12 years). In total, 47 patients (62%) had ileocolic resection (group II). Logistic regression analysis revealed that a longer time between onset and exacerbation of this disease, the presence of stenosis and extraintestinal manifestations were independent predictors of failure of nonsurgical treatment. CONCLUSION: Prolonged medical treatment is effective in only one third of the clinically admitted patients. It should be applied with caution particularly in patients exhibiting stenosis, extraintestinal manifestations or a known history of Crohn's disease of more than 5 years.

Adult↗
PubMed2000

Laparoscopic-assisted vs. open ileocolic resection for Crohn's disease. A comparative study.

BACKGROUND: The objective of this study was to compare laparoscopic-assisted ileocolic resection for Crohn's disease of the distal ileum with open surgery in two consecutive groups of patients. METHODS: From 1995 until 1998, 48 patients underwent open ileocolic resection at the Academic Medical Center (AMC) in Amsterdam, while 30 patients had laparoscopic-assisted ileocolic resection at the Leiden University Medical Center (LUMC). Patient characteristics, perioperative course, and recovery were compared. Differences between the groups were tested using Student's t-test for independent groups and chi-square tests when appropriate. RESULTS: The open and the laparoscopic patient groups were comparable for age, gender, body mass index (BMI), prior abdominal surgery, and length of resected bowel. The conversion rate was 6.6%. Laparoscopic operating times (138+/-SD 36 min) were significantly longer than those observed in the open group (104+/-SD 34 min). Discharge was significantly earlier in the laparoscopic group than the open group (5.7 vs 10.2 postoperative days, p<0.007). Postoperative morbidity did not differ significantly between the patients treated traditionally (14.6%) and laparoscopically (10%). CONCLUSION: Compared to open surgery, laparoscopic ileocolic resection for Crohn's disease is associated with similar morbidity rates, a shorter hospital stay, and improved cosmetic results, justifying the laparoscopic approach as the procedure of choice.

Adult↗
PubMed2000

Laparoscopic-assisted vs open colectomy for severe acute colitis in patients with inflammatory bowel disease (IBD): a retrospective study in 42 patients.

BACKGROUND: Inflammatory bowel disease (IBD) can be complicated by severe acute colitis. Emergency colectomy is mandatory if patients do not respond to intensive medical therapy. A minimally invasive approach such as laparoscopic-assisted colectomy might be beneficial in these patients. Therefore, we set out to assess the feasibility and the safety of emergency laparoscopic-assisted colectomy in IBD patients with severe acute colitis. METHODS: A total of 42 consecutive patients underwent an emergency colectomy with end-ileostomy. Ten patients had laparoscopic-assisted colectomy, and 32 had open colectomy. Pre- and perioperative parameters, morbidity, and mortality were analyzed. RESULTS: The two groups were comparable for patient characteristics. There were no conversions in the laparoscopic group. The operation time was longer in the laparoscopic group than in the open group (271 vs 150 min; p < 0.001), but the hospital stay was shorter (14.6 vs 18.0 days; p = 0.05). Complications were similar for the two groups. CONCLUSION: Laparoscopic-assisted colectomy in IBD patients with severe acute colitis is feasible and as safe as open colectomy.

Acute Disease↗
PubMed2000

Gallbladder motility in Crohn disease: influence of disease localization and bowel resection.

BACKGROUND: Patients with Crohn disease (CD) have an increased risk of developing gallstones. Among other factors, gallbladder motility may have a role in the pathogenesis of gallstone formation. We have evaluated whether gallbladder motor function is affected in Crohn disease with special emphasis on the influence of disease localization and previous bowel resection. METHODS: Thirty-seven patients (20 females and 17 males, age 36 +/- 2 years) with inactive Crohn disease (CDAI < 150) were studied: 15 patients after ileocecal resection and 22 non-operated patients; 12 had small bowel disease and 10 had large bowel disease. Nineteen healthy subjects (10 female; 9 male, age 30 +/- 2 years) served as controls. Gallbladder volumes were measured in the fasting state and at regular intervals for 2 h after ingestion of a solid meal (780 kcal). Blood samples were drawn at regular intervals for determination of cholecystokinin (CCK) and peptide YY (PYY). RESULTS: Fasting gallbladder volumes were significantly (P < 0.05) reduced in patients with large bowel disease (20.8 +/- 2.1 ml) or after ileocecal resection (18.3 +/- 2.4 ml) compared to patients with small bowel disease (28.0 +/- 2.1 ml) and controls (27.2 +/- 1.8 ml). Fasting plasma CCK levels were significantly (P < 0.05) higher in patients with large bowel disease or after ileocecal resection compared to patients with small bowel disease and controls. Postprandial gallbladder emptying and endogenous plasma CCK and PYY secretion in patients with Crohn disease were not different from controls. CONCLUSIONS: Fasting gallbladder volume is decreased and fasting plasma CCK levels are increased in patients with Crohn disease of the large bowel and patients after ileocecal resection. Postprandial gallbladder motility, CCK and PYY release were not affected in patients with Crohn disease.

Adult↗
PubMed2000

Cellular immune response to human cartilage glycoprotein-39 (HC gp-39)-derived peptides in rheumatoid arthritis and other inflammatory conditions.

OBJECTIVE: To study the specificity of the peripheral blood mononuclear cell (PBMC) response to peptides derived from human cartilage glycoprotein-39 (HC gp-39) in patients with rheumatoid arthritis (RA) and the correlation between this response and disease activity. METHODS: RA patients, patients with systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD) or osteoarthritis (OA) and healthy controls were studied. All individuals were typed for HLA-DRB1 and their disease activity score was documented. Proliferation of PBMC was measured following incubation with five different HC gp-39-derived peptides, selected by the use of a DR4 (DRB1*0401) binding motif. RESULTS: A proliferative response to one of the five peptides (peptide 259-271 at 10 microg/ml) was more often observed in RA patients than in healthy controls (P=0.001). RA patients who expressed DRB1*0401 more often showed a response against this peptide than RA patients who did not express this RA-associated haplotype. This response was not RA-specific since patients with IBD or OA also showed a response significantly more frequently than healthy controls (P:=0.02 and P=0.03 respectively). However, the level of the response against peptide 259-271 correlated with disease activity in RA patients but not in patients with IBD or SLE. Increased responses to HC gp-39 263-275 were found in patients with IBD or OA; a trend towards such a response failed to reach significance in RA patients in this study. CONCLUSION: In RA patients as well as in patients with other inflammatory conditions, HC gp-39-derived peptides may be targets of the T-cell-mediated immune response. In the RA patient group the immune response to HC gp-39-derived peptide 259-271 correlated with disease activity.

Adipokines↗
PubMed2000

Raised human cartilage glycoprotein-39 plasma levels in patients with rheumatoid arthritis and other inflammatory conditions.

OBJECTIVE: To evaluate plasma human cartilage glycoprotein (HC gp-39) as a possible marker for the presence and/or activity of rheumatoid arthritis (RA) and other inflammatory conditions. BACKGROUND: HC gp-39 is a secretory product of chondrocytes, synovial cells, macrophages, and neutrophils. HC gp-39, also described as YKL-40, was found to be a marker of joint disease and tissue injury in RA and various other diseases. METHODS: Levels of HC gp-39 were determined by a sandwich enzyme linked immunosorbent assay (ELISA) in 47 patients with RA, 47 with osteoarthritis (OA), 24 with systemic lupus erythematosus (SLE), 24 with inflammatory bowel disease (IBD), and in 47 healthy controls. A disease activity score was assessed in the patients with RA, SLE, and IBD. RESULTS: The plasma level of HC gp-39 in the RA patient group was significantly higher than in the other patient groups and healthy controls. The level in patients with OA, SLE, and IBD was also significantly higher than the HC gp-39 level found in the healthy control group. HC gp-39 levels in patients with RA correlated positively with the ESR and IgM rheumatoid factor level but not with other variables of disease activity. In the patients with SLE and IBD no correlation was found with the disease activity score. CONCLUSION: The plasma level of HC gp-39 is increased in inflammatory conditions with and without joint disease (SLE, IBD, OA, and RA). Thus increased levels of HC gp-39 do not only reflect joint disease but also reflect inflammation or tissue degradation in various conditions. Notably, the highest level of HC gp-39 was found in patients with RA. Only in the RA patient group was a correlation between HC gp-39 plasma levels and some laboratory variables of disease activity found.

Adipokines↗
PubMed1999

Infliximab for the treatment of fistulas in patients with Crohn's disease.

BACKGROUND: Enterocutaneous fistulas are a serious complication of Crohn's disease and are difficult to treat. Infliximab, a chimeric monoclonal antibody to tumor necrosis factor alpha, has recently been developed as a treatment for Crohn's disease. We conducted a randomized, multicenter, double-blind, placebo-controlled trial of infliximab for the treatment of fistulas in patients with Crohn's disease. METHODS: The study included 94 adult patients who had draining abdominal or perianal fistulas of at least three months' duration as a complication of Crohn's disease. Patients were randomly assigned to receive one of three treatments: placebo (31 patients), 5 mg of infliximab per kilogram of body weight (31 patients), or 10 mg of infliximab per kilogram (32 patients); all three were to be administered intravenously at weeks 0, 2, and 6. The primary end point was a reduction of 50 percent or more from base line in the number of draining fistulas observed at two or more consecutive study visits. A secondary end point was the closure of all fistulas. RESULTS: Sixty-eight percent of the patients who received 5 mg of infliximab per kilogram and 56 percent of those who received 10 mg per kilogram achieved the primary end point, as compared with 26 percent of the patients in the placebo group (P=0.002 and P=0.02, respectively). In addition, 55 percent of the patients assigned to receive 5 mg of infliximab per kilogram and 38 percent of those assigned to 10 mg per kilogram had closure of all fistulas, as compared with 13 percent of the patients assigned to placebo (P=0.001 and P=0.04, respectively). The median length of time during which the fistulas remained closed was three months. More than 60 percent of patients in all the groups had adverse events. For patients treated with infliximab, the most common were headache, abscess, upper respiratory tract infection, and fatigue. CONCLUSIONS: Infliximab is an efficacious treatment for fistulas in patients with Crohn's disease.

Adult↗