Clinical Recurrence Of Crohn's Disease Research Articles

High-Dose Vitamin D Does Not Prevent Postoperative Recurrence of Crohn’s Disease in a Randomized Placebo-Controlled Trial

Vitamin D deficiency is common in Crohn's disease (CD). High-dose vitamin D had anti-inflammatory effects in preclinical studies and trials of patients with CD. We performed a randomized trial to determine whether high-dose vitamin D prevents postoperative recurrence of CD after ileocolonic resection. Patients with CD after ileocolonic resection with ileocolonic anastomosis were assigned randomly to groups given weekly 25,000 IU oral vitamin D (n= 72) or placebo (n= 71) for 26 weeks, at 17 hospitals in The Netherlands and Belgium, from February 2014 through June 2017. Patients were assessed at baseline and at weeks 2, 6, 12, and 26 for laboratory and clinical parameters, and underwent ileocolonoscopy at 26 weeks. The primary end point was endoscopic recurrence (modified Rutgeerts score, ≥i2b, as assessed by blinded readers) at 26 weeks. Secondary end points included clinical recurrence (Crohn's disease activity index, ≥220), quality of life (measured by the 36-Item Short Form Health Survey, Inflammatory Bowel Disease Questionnaire, and EuroQol, a 5-dimension questionnaire), and outcomes associated with the baseline serum concentration of vitamin D. In the vitamin D group, serum levels of 25-hydroxy vitamin D increased from a median of 42 nmol/L at baseline to 81 nmol/L at week 26 (P < .00001), whereas levels did not change significantly in the placebo group and remained unchanged at 43 nmol/L. In the intention-to-treat analysis, the proportion of patients with endoscopic recurrence at 26 weeks did not differ significantly between the vitamin D vs the placebo group (58% vs 66%; P= .37). The cumulative rate of clinical recurrence did not differ significantly between the groups (18.1% in the vitamin D group vs 18.3% in the placebo group; P= .91). Quality of life improved slightly over time in both groups, but did not differ significantly between groups (P= .07). There were few adverse events in either group. High-dose vitamin D, compared with placebo, did not reduce the incidence of postoperative endoscopic or clinical recurrence of CD in patients who underwent ileocolonic resection with ileocolonic anastomosis. ClinicalTrials.gov no: NCT02010762.

Pericardial Manifestations in Inflammatory Bowel Disease: A Report of Two Cases

Abstract Pericardial involvement in the setting of inflammatory bowel disease can occur not only as an adverse event related to medical therapy but also as an extraintestinal manifestation of the disease itself. In the following case series, we describe 2 cases of pericarditis in patients diagnosed with Crohn disease. Our first case reviews the clinical presentation of acute pericarditis as an adverse event associated with anti-tumor necrosis factor therapy. In contrast, our second patient is a case of acute pericarditis as a precursor of the clinical recurrence of Crohn disease following operative resection. Pericardial disease should be considered in the differential diagnosis of acute and subacute presentations of chest discomfort and shortness of breath in patients with inflammatory bowel disease.

Tu1321 Systematic Review With Meta-Analysis of Prospective Studies: Anti-TNFs for Prevention of Postoperative Crohn's Disease Recurrence

Background Although promising, the evidence supporting the use of anti-tumor necrosis factor agents (anti-TNFs) in the postoperative Crohn's disease (CD) is still based on limited experiences. Aim We aimed to conduct a meta-analysis of prospective studies evaluating the efficacy and safety of anti-TNFs for prevention of postoperative recurrence (POR) in CD. Methods MEDLINE, EMBASE, Web of Science, Cochrane database and conference proceeding abstracts were searched. The primary outcome measures were patients achieving remission or POR as defined by the primary studies and pooled. Results Six prospective studies were included. The rate of endoscopic recurrence (ER) was significantly lower in anti-TNFs (9.2%, 7/76) compared with non-biologic control group (61.5%, 83/135); odds ratio (OR) 0.05, 95% confidence interval(CI) 0.02-0.13; P<0.001). Severe ER also less frequently occurred in the anti-TNFs group (1.6%, 1/64) than the control group (32.7%, 18/55, OR 0.10; P=0.04). Significantly lower proportion of patients in the anti-TNFs group developed clinical recurrence (3.4%, 2/59) compared with the control arm (41.1%, 49/119; OR 0.1; P<0.001). More anti-TNFs-treated patients (86.5%, 45/52) maintained in clinical remission compared with the control group (58.1%, 43/74, OR 4.05; 95%CI 1.60-10.29, P <0.01). The documented adverse effects were comparable between the two groups (antiTNFs 44.9% (22/49) vs. control 52.5% (42/80), P =0.69). Conclusion Anti-TNFs are superior to non-biologic agents in preventing endoscopic and clinical recurrence of CD without causing more adverse effects.

Prevention of post-operative recurrence of Crohn’s disease

Endoscopic and clinical recurrence of Crohn's disease (CD) is a common occurrence after surgical resection. Smokers, those with perforating disease, and those with myenteric plexitis are all at higher risk of recurrence. A number of medical therapies have been shown to reduce this risk in clinical trials. Metronidazole, thiopurines and anti-tumour necrosis factors (TNFs) are all effective in reducing the risk of endoscopic or clinical recurrence of CD. Since these are preventative agents, the benefits of prophylaxis need to be weighed-against the risk of adverse events from, and costs of, therapy. Patients who are high risk for post-operative recurrence should be considered for early medical prophylaxis with an anti-TNF. Patients who have few to no risk factors are likely best served by a three-month course of antibiotics followed by tailored therapy based on endoscopy at one year. Clinical recurrence rates are variable, and methods to stratify patients into high and low risk populations combined with prophylaxis tailored to endoscopic recurrence would be an effective strategy in treating these patients.

Adalimumab Is More Effective Than Azathioprine and Mesalamine at Preventing Postoperative Recurrence of Crohn's Disease: A Randomized Controlled Trial

Postsurgical recurrence of Crohn's disease (CD) is very frequent and, to date, only infliximab has been shown to be useful in preventing it. The efficacy of adalimumab (ADA) is poorly known. We evaluated whether the administration of ADA after resective intestinal surgery reduces postoperative CD recurrence. We randomly assigned 51 patients with CD who had undergone ileocolonic resection to receive after 2 weeks from surgery ADA at the dose of 160/80/40 mg every two weeks, azathioprine (AZA) at 2 mg/kg/day, or mesalamine at 3 g/day, and they were followed up for 2 years. The primary end point was the proportion of patients with endoscopic and clinical recurrence. Secondary end point was the assessment of quality of life by means of a previously validated questionnaire. The rate of endoscopic recurrence was significantly lower in ADA (6.3%) compared with the AZA (64.7%; odds ratio (OR)=0.036 (95% confidence interval (CI) 0.004-0.347)) and mesalamine groups (83.3%; OR=0.013 (95% CI 0.001-0.143)). There was a significantly lower proportion of patients in clinical recurrence in the ADA group (12.5%) compared with the AZA (64.7%; OR=0.078 (95% CI 0.013-0.464)) and mesalamine groups (50%; (OR=0.143 (95% CI 0.025-0.819)). The quality of life was higher in the ADA (202) than in the AZA (90; OR=0.028 (95% CI 0.004-0.196)) and mesalamine groups (98; OR=0.015 (95% CI 0.002-0.134)). The administration of ADA after intestinal resective surgery was greatly effective in preventing endoscopic and clinical recurrence of CD. Further larger studies are necessary to confirm the therapeutic advantage and to show the economic implications of biologic therapy in this field.

Crohn's disease recurrence after total proctocolectomy with definitive ileostomy

Background Total proctocolectomy with definitive ileostomy is the ultimate treatment for refractory colonic Crohn's disease (CD). Aim of the study was to report the outcome of Crohn's disease patients after total proctocolectomy with definitive ileostomy. Patients and methods Between 1990 and 2005, 55 patients underwent total proctocolectomy with definitive ileostomy for Crohn's disease in our institution. None of them received preventive post-operative treatment. We studied clinical recurrence, need for immunosuppressants (IS), anti-TNF therapy and re-operation in this retrospective cohort. Results Median follow-up was 5.4 years. Probabilities of clinical Crohn's disease recurrence were 4%, 27% and 39% at 1, 5 and 8 years, respectively. In multivariate analysis, clinical recurrence rate was significantly higher for patients with penetrating disease behaviour (RR 1.7 IC95% [1.5–19], p = 0.05) and absence of perianal disease (RR = 1.6, IC95% [1.4–10]; p = 0.01). Clinical recurrences were located in terminal ileum in all cases and treated medically in 9 of 16 patients including IS or anti TNF agents in 7 cases. Probabilities of treatment with immunosuppressants or anti-TNF therapy were 4%, 15% and 15% at 1, 5 and 8 years, respectively. Nearly one third of the patients (29%) underwent surgery for mechanical complications (N = 11) and/or CD recurrence (N = 7). Probabilities of reoperation for Crohn's disease recurrence were 0%, 10% and 18% at 1, 5 and 8 years, respectively. Conclusion Recurrence after total proctocolectomy with definitive ileostomy for Crohn's disease is not uncommon, and in our series often required immunosuppressants or surgical procedure.

TGF-β1 and IGF-1 Production and Recurrence of Crohn's Disease After Ileo-Colonic Resection

Recurrence after surgery is a major problem in the treatment of Crohn's disease (CD). Alteration of healing processes may play a role in this phenomenon. Transforming growth factor beta (TGF-beta) and insulin-like growth factor (IGF-1) have pro-fibrogenic properties and are involved in wound-healing mechanisms. The aim of this study was to assess their role in the CD recurrence after ileo-colonic resection. Twenty patients with CD, who underwent ileo-colonic resection in the period between 1999 and 2005, were enrolled in this study. Tissue samples were obtained from macroscopically diseased and healthy ileum. The TGF-beta1 and IGF-1 mRNAs were quantified by real-time polymerase chain reaction using glyceraldehyde 3-phosphate dehydrogenase as the housekeeping gene. Histological severity of the disease was assessed to quantify the ileal inflammation. Patients' follow-up was investigated. Comparisons and correlations were carried out with nonparametric tests and survival analysis was performed. Histological inflammation was moderately severe in the diseased bowel, while it was absent in healthy segments (P < 0.01). TGF-beta1 production in healthy bowels showed a direct correlation with clinical CD recurrence (tau = 0.43, P = 0.04) and survival analysis showed that patients who expressed high TGF-beta1 mRNA transcripts in healthy intestines had higher cumulative recurrence rates than those who expressed low TGF-beta1 mRNA levels (P = 0.02). Our study suggests that the high levels of TGF-beta1 in healthy bowels of patients who undergo ileo-colonic resection for CD are associated with early clinical disease recurrence, while there seems to be no association between IGF-1 and CD recurrence.