Maintenance of remission in Crohn's disease

When remission of Crohn's disease is achieved, the next goal is to maintain long-term remission. Aminosalicylates may be recommended for maintenance remission, even though the results are less consistent than those observed in ulcerative colitis. The benefit is mainly observed in the post-surgical setting and in patients with ileitis, and with a prolonged disease duration. Corticosteroids are not effective in maintaining remission and should not be used for this indication. Azathioprine and 6-mercaptopurine are effective in maintaining remission. Maintenance benefits remain significant for patients who continued with the therapy for up to 5 years. Methotrexate has also been found to be effective in maintaining remission in Crohn's disease in patients who have responded acutely to methotrexate. Cyclosporine has not been found to be an effective maintenance agent. Mycophenolate mofetil could be considered a therapy in patients who are either allergic to azathioprine or in whom azathioprine failed to induce remission. The use of infliximab may change the future approach to maintenance therapy for Crohn's disease. Patients who responded clinically to infliximab have maintained their clinical response when receiving repeat infusions at 8-week intervals. In patients refractory to other therapies, infliximab may be effective in maintaining remission.     

Supplementary enteral nutrition maintains remission in paediatric Crohn's disease.

BACKGROUND--Liquid diets given enterally combined with "bowel rest'' are efficacious in the treatment of active Crohn''s disease, but rapid recrudescence of gastrointestinal symptoms after resumption of a normal diet is common. AIMS--This study examined whether continuation of enteral nutrition as a nocturnal supplement to an ad libitum daytime intake of a normal diet increased the length of remission of Crohn''s disease in children. PATIENTS AND METHODS--Children and adolescents with active Crohn''s disease treated successfully with exclusive enteral nutrition were classified retrospectively according to whether they continued supplementary enteral nutrition or not. Time to relapse and linear growth were compared between the two cohorts. RESULTS--Between January 1986 and December 1992, 65 patients aged 7-17 years (mean (SD) 13.6 (2.1) years) (36 males, 29 females) with Crohn''s disease in exacerbation were treated for > or = four weeks by bowel rest and nasogastric tube feeding of an oligopeptide or amino acid based formula. At first follow up visit, remission (fall in Paediatric Crohn''s Disease Activity Index, PCDAI to < or = 20) was achieved in 47 of 65 (72%) patients. Subsequently, 20 of these 47 (43%) relapsed by six months and 28 of 47 (60%) by 12 months. Patients who continued nasogastric supplementary feeding (n = 28) after resumption of an otherwise normal diet remained well longer than those who discontinued nocturnal supplements completely (n = 19) (p < 0.02). Furthermore, continued use of nasogastric supplements before completion of puberty was associated with improved linear growth. CONCLUSION--After successful treatment of active Crohn''s disease by exclusive enteral nutrition, supplementary enteral nutrition without restriction of normal diet is associated with prolongation of remission and improved linear growth in children and adolescents.     

英夫利昔在克罗恩病维持缓解中的应用

克罗恩病(Crohn disease,CD)是一种由于环境、感染、遗传因素等诸多因素综合作用后导致的免疫功能紊乱,最终表现为反复发作的肠道炎症、溃疡和(或)全身症状。英夫利     

Maintenance of medically induced remission of Crohn's disease

The natural history of Crohn's disease is characterized by recurring flares alternating with periods of inactive disease and remission. This implies that most patients need to take medication for a large period of their life, mostly for maintenance of remission and, intermittently, additional therapy during a flare. Low-dose systemic corticosteroids are not effective in maintaining remission and should not be used for this indication. There is a trend towards a prolonged time to relapse in patients in remission who are treated with budenoside, a corticosteroid with high topical anti-inflammatory activity and low systemic activity. Azathioprine and 6-mercaptopurine are effective in maintaining remission. Maintenance benefits remain significant for patients who continued with the therapy for up to 5 years. Methotrexate has also been found to be effective in maintaining remission in Crohn's disease in patients who have responded acutely to methotrexate. Cyclosporine has not been found to be an effective maintenance agent. Only a few studies in small numbers of patients have been published on the use of tacrolimus. There is a lack of convincing evidence of efficacy of mycophenolate mofetil. The use of anti-TNF agents may change the future approach to maintenance therapy for Crohn's disease. Patients who responded clinically to infliximab, adalimumab and certolizumab have maintained their clinical response when receiving repeat infusions or subcutaneous injections, respectively. In patients refractory to other therapies, infliximab may be effective in maintaining remission.     

Long-term outcome of Crohn's disease following corticosteroid-induced remission

INTRODUCTION: Corticosteroids are the gold standard in the treatment of moderate to severe Crohn's disease but are often associated with severe and potentially dangerous side effects. Despite an initial clinical response many patients become steroid dependent or require further steroid courses in the long term. The aim of the present study was to assess the probability of the need for further steroid treatment in Crohn's disease patients following steroid-induced remission and to establish if clinical variables can predict further steroid needs. PATIENTS AND All METHODS: patients at their first steroid course and with corticosteroid-induced remission, defined as a Crohn's Disease Activity Index (CDAI) <150, 4 wk after steroid weaning, were studied and observed at follow-up for 12 months. The main outcome was clinical relapse requiring further steroid treatment. Statistical analysis was performed using the Kaplan-Meier method and multivariable Cox proportional hazard regression model taking into consideration gender, age at diagnosis, disease location and behavior, smoking habits, CDAI score before steroid treatment, and C reactive protein values at steroid weaning, as covariates. RESULTS: A total of 77 patients with steroid-induced remission were included. One-year follow-up was available in 75 of the 77 patients (97.4%). During follow-up 49 of 75 patients (65.3%) maintained remission or presented mild relapse not requiring steroids while 26 of 75 patients (34.6%) had moderate to severe relapse requiring further steroid treatment. The cumulative probability of a course free from steroids was 93.3%, 82.6%, 78.6%, and 66.6% at 3, 6, 9, and 12 months, respectively. At multivariate analysis, increased C reactive protein at steroid weaning and penetrating complications were independent risk factors for further steroid requirement (OR 5.57, 95% CI 1.20-25.91, P= 0.001 and OR 4.20, 95% CI 1.76-10.04, P= 0.005, respectively). CONCLUSION: Despite an initial clinical response and successful steroid tapering, 35% of patients required further steroid treatment within 1 yr. An increased C reactive protein value, at steroid weaning, despite clinical remission, and penetrating complications may predict further steroid requirement in already steroid responsive patients.     

Microinflammation in patients with Crohn's disease in clinical remission

Background and aimsIt is not clear whether Crohn's disease patients in clinical remission (Crohn's disease activity index < 150) display normal concentrations of inflammation sensitive biomarkers. Our goal in this work was to explore the intensity of the microinflammatory response in a group of Crohn's disease patients in clinical remission.MethodsHigh sensitivity C-reactive protein, quantitative fibrinogen, erythrocyte sedimentation rate as well as platelet and leukocyte counts were examined in a group of 76 patients with Crohn's disease in remission and in 228 matched controls.ResultsCrohn's disease patients in clinical remission displayed a statistically significant (p < 0.001) elevated concentration of hs-CRP (4.83 ± 3.8 mg/l) compared to controls (1.05 ± 2.9 mg/l). All other bio-markers were also significantly higher in Crohn's disease patients in remission compared to controls. Similar results were obtained in a subgroup of Crohn's disease patients with very low disease activity — CDAI < 75.ConclusionsClinical remission is not equivalent to biochemical remission raising a question concerning the true definition of remission in Crohn's disease.     

Nutritional deficiencies in patients with Crohn's disease in remission

BACKGROUND: Patients with Crohn's disease (CD) are at risk of developing nutritional deficiencies, especially because of restrictive diets. The aim of our study was to assess food intake and the status for vitamins and trace elements in nonselected CD patients in clinical remission. METHODS: A total of 54 consecutive CD patients (28 females, 26 males, 39 +/- 2 years of age [mean +/- SD]) in clinical remission for >3 months underwent body composition, resting energy expenditure, nutrient intake, and plasma concentration assessment, and were compared with 25 healthy controls (16 females, 9 males, 38 +/- 3 years old). RESULTS: According to the nutritional risk index, 37 patients (70%) were not malnourished, 12 were at moderate risk, and 4 were at severe risk for malnutrition. Fat mass was lower in patients in remission compared with controls (P = 0.04). The mean daily energy intake was comparable between patients (2218 +/- 92 kcal/day) and controls (2066 +/- 101 kcal/day), covering their needs. No significant difference was observed for macronutrient intake in comparison with controls; compared to controls, female CD patients had lower intakes of beta-carotene (P < 0.005), vitamins B1 (P < 0.05), B6 (P < 0.01), and C (P < 0.005), and magnesium (P < 0.01). They had significantly higher intakes of zinc (P < 0.01). Male CD patients had lower intakes of beta-carotene and vitamin C (P < 0.05). More than 50% of patients had low plasma concentrations of vitamin C (84%), copper (84%), niacin (77%), and zinc (65%). CONCLUSIONS: In CD patients in remission, macronutrient needs are usually covered by food intake. However, micronutrient deficiencies are frequent and call for specific screening and treatment.     

Maintenance of surgically induced remission of Crohn's disease

At 1 year after a first resection, up to 80% of patients show an endoscopic recurrence, 10-20% have clinical relapse, and 5% have surgical recurrence. Smoking is one of the most important risk factors for postoperative recurrence. Preoperative disease activity and the severity of endoscopic lesions in the neoterminal ileum within the first postoperative year are predictors of symptomatic recurrence. Mesalazine is generally the first-line treatment used in the postoperative setting but still provokes considerable controversy as to its efficacy, in spite of the results of a meta-analysis. Immunosuppressive treatment (azathioprine, 6-mercaptopurine) is based on scant evidence but is currently used as a second-line treatment in postsurgical patients at high risk for recurrence, with symptoms or with early endoscopic lesions in the neoterminal ileum. Nitroimidazole antibiotics (metronidazole, ornidazole) are also effective in the control of active Crohn's disease in the postoperative setting. Given their known toxicity, they may be used as a third-line treatment as initial short-term prevention therapy rather than in the long term. Conventional corticosteroids, budesonide or probiotics have no proven role in postoperative prophylaxis. Infliximab has not as yet been studied for use in the prevention of relapse after surgery.     

Azathioprine for prevention of postoperative recurrence in Crohn's disease: a retrospective study.

BACKGROUND: The efficacy of azathioprine (AZA) in chronically active Crohn's disease (CD) is well established. Whether this drug is also useful to prevent recurrences after surgery is unknown. We report here our experience of AZA in this therapeutic goal. METHODS: Between 1987 and 1996, 38 patients with CD were treated with AZA to prevent postoperative recurrence. Twenty-three of these had undergone a curative resection with removal of all previously involved parts of the gut. In the other 15 patients, resection was limited to the parts of the gut macroscopically abnormal at the time of surgery; those parts that were previously involved but normal at this time were conserved. The operative procedures were ileocolonic resection (n = 18), subtotal colectomy with ileorectal anastomosis (n = 12), coloproctectomy with ileo-anal anastomosis (n = 4) or ileostomy (n = 2), ileal resection (n = 1) and segmental colectomy (n = 1). Twelve patients had been treated previously with AZA before surgery; in 26 patients, AZA was started within the 2 months following surgery. RESULTS: The median duration of postoperative follow-up was 29 months. Probabilities of clinical recurrence according to the Kaplan-Meier method were 9, 16 and 28% at 1, 2 and 3 years, respectively. For the 25 patients who had a colonoscopy or a small bowel barium X-ray during the follow-up, probabilities of anatomical recurrence were 16, 36 and 59% at 1, 2 and 3 years, respectively. The probability of anatomical recurrence was significantly higher in patients who had segments of the gut previously involved but not removed because they were macroscopically normal at the time of surgery. CONCLUSION: In patients treated with AZA, the rate of postoperative endoscopic recurrence was lower than that previously reported in untreated patients. Our results suggest that AZA should be evaluated prospectively for prevention of postoperative CD recurrence, at least in high-risk patients.     

A comparative study of metronidazole and sulfasalazine for active Crohn's disease: the cooperative Crohn's disease study in Sweden. II. Result

Seventy-eight patients with active Crohn's disease participated in a randomized, double-blind, cross-over trial. The study comprised two 4-mo period. The purpose was to test the efficacy of metronidazole in comparison with that of sulfasalazine. As the main evaluation criteria the Crohn's Disease Activity Index and plasma levels of orosomucoid were chosen. In the first period no difference in efficacy as measured by Crohn's Disease Activity Index was found between the treatment groups. The reduction of the plasma orosomucoid level was significantly more pronounced in the metronidazole group. The hemoglobin concentration increased more in this group than in the sulfasalazine group, possibly due to a toxic effect of sulfasalazine. The erythrocyte sedimentation rate decreased similarly with both drugs. In 15 patients who had active disease throughout the first period, Crohn's Disease Activity Index decreased significantly in the second period for those who switched to metronidazole, but not for those who switched to sulfasalazine. After crossover, no apparent further change in Crohn's Disease Activity Index occurred in either of the treatment groups among patients who had responded favorably in the first period. The plasma concentration of orosomucoid increased significantly among the patients in the sulfasalazine group but not in the metronidazole group. It is therefore concluded that metronidazole is slightly more effective than sulfasalazine in the treatment of crohn's disease. It is worthwhile switching the drug regimen from sulfasalazine, when it fails, to metronidazole, but not from metronidazole to sulfasalazine.     

Azathioprine for prevention of postoperative recurrence in Crohn's disease.

The clinical relapse rate after surgery for Crohn's disease in prospective studies is about 40% at 2 years in people who receive no postoperative prophylaxis. Thiopurines (azathioprine and 6-mercaptopurine) are likely to be the most effective pharmacotherapy for preventing postoperative relapse: about four patients need to be treated for 2 years to prevent one clinical relapse. The factors that help to identify patients at highest risk of relapse are discussed, along with the reasons for the choice of thiopurine, dose and duration of therapy. Other measures to reduce the relapse rate are addressed.     

Infliximab as a bridge to remission maintained by antimetabolite therapy in Crohn's disease: A retrospective study

BackgroundInfliximab withdrawal in patients with Crohn's disease on concomitant antimetabolite therapy is considered to be superior if obtained after a maintenance therapy period compared to induction alone.MethodsWe retrospectively analyzed the outcome of Crohn's disease patients treated with infliximab and an antimetabolite after infliximab was withdrawn using induction alone or induction plus at least 1-year of maintenance therapy. The time to relapse was analyzed using univariate and multivariate analyses. The model was adjusted according to the period of infliximab withdrawal.ResultsA total of 92 patients were included, 54 in the induction alone group. The patient characteristics were identical in the two groups except for the period of infliximab withdrawal. After a median follow-up period of 47.1 (interquartile range = 4.4–110.2) months, 66 patients (72%) experienced a relapse. After a year-adjustment, no significant difference was observed between the two groups. Based on year-adjusted multivariate analysis, the risk factors for relapse were active smoking, previous antimetabolite failure, and perianal disease. After relapse, 53 patients (80%) were retreated with infliximab. After infliximab retreatment, clinical remission was observed in 47 patients (89%) at weeks 8–10.ConclusionIn Crohn's disease patients, the probability of relapse on antimetabolite therapy after infliximab withdrawal was not superior after a 1-year scheduled maintenance therapy as compared with an induction alone.