Pre‐operative management is associated with low rate of post‐operative morbidity in penetrating Crohn’s disease

Aliment Pharmacol Ther 2010; 32: 459–465

Summary

Background Ileocaecal resection for penetrating Crohn’s disease is still challenging with a high rate of post‐operative morbidity and faecal diversion. Aim To report retrospectively the results of pre‐operative management for penetrating Crohn’s disease focusing on the rate of post‐operative major morbidities and need for faecal diversion. Methods Between 1997 and 2007, 78 patients with penetrating Crohn’s disease underwent a first ileocaecal resection after a pre‐operative management consisting in bowel rest, nutritional therapy, intravenous antibiotics, weaning off steroids and immunosuppressors, and drainage of abscesses when appropriate. Results Resection was performed for terminal ileitis associated with (n = 41), abscesses (n = 37) or both (n = 5). A pre‐operative nutritional therapy was performed in 50 patients (68%) for 23 days (range, 7–69 days) along with a weaning off steroids and immunosuppressors. A diverting stoma was performed for six patients (7.7%). There was no post‐operative death. Post‐operative complications were classified as minor in 10 patients (12.8%), and major in four patients (5%). Overall, the post‐operative course was uneventful in 58 patients (74%). Conclusion Pre‐operative management for penetrating Crohn’s disease allowed ileocaecal resection with low rates of post‐operative morbidity and faecal diversion.     

Meta‐analysis: polymorphisms in TNF‐α gene promoter and Crohn’s disease

Aliment Pharmacol Ther 2010; 32: 159–170

Summary

Background Tumour necrosis factor alpha (TNF‐α) is involved in the pathogenesis of Crohn’s disease (CD). However, results on the association between the polymorphisms in TNF‐α promoter and the risk of CD are inconsistent. Aim To perform a quantitative synthesis for the genetic polymorphisms in TNF‐α promoter and CD risk. Methods Databases were searched (up to 2009) and 31 studies were included. Risks of CD associated with the polymorphisms in TNF‐α promoter were assessed. Results Overall, individuals with ‐1031 TC+CC genotype had a slightly increased risk to develop CD compared with individuals with ‐1031 TT genotype (OR, 1.32; 95% CI, 1.03–1.70). In the further stratified analysis, we found Asians with the ‐1031T>C, ‐863 C>A and ‐857 C>T variant polymorphisms have almost one and a half CD risk compared with other genotypes (OR, 1.58; 95% CI, 1.16–2.15; OR, 1.55; 95% CI, 1.18–2.02; OR, 1.54; 95% CI, 1.19–1.99 respectively). We did not find ‐308 G>A variant associated with CD location and disease behaviours in stratified analysis. Conclusions TNF‐α polymorphisms in the promoter region might be used as a biomarker for CD risk prediction. Larger studies with mixed ethnicity subjects and stratified by clinical and sub clinical characteristics are needed to validate our findings.     

A claims‐based Markov model for Crohn’s disease

Aliment Pharmacol Ther 2010; 32: 448–458

Summary

Background Crohn’s disease is a chronic condition that often presents in early adulthood. Aim To evaluate health care costs and costs per quality‐adjusted life year (QALY) for Crohn’s disease. Methods A Markov model was developed using administrative claims data for patients aged ≥ 18 years with ≥ 3 years of continuous enrolment from 2000 to 2008 and ≥2 Crohn’s disease claims. Disease states (remission, mild–moderate, moderate–severe, and severe–fulminant) were defined using the American College of Gastroenterology treatment guidelines criteria. Transition probabilities were calculated from consecutive 6‐month periods. Costs were determined from paid claims and QALY utilities were obtained from the literature. The model assumed a 30‐year‐old patient at the time of entry into the model. Results There were 40 063 patients identified, with a total of 420 773 cycles [remission (197 111; 46.8%), mild–moderate (44 024; 10.5%), moderate–severe (132 695; 31.5%), severe‐fulminant (46 925; 11.2%)]. The costs/QALY for remission, mild–moderate, moderate–severe, and severe–fulminant disease states respectively were $2896, $8428, $11 518 and $69 277 for males and $2896, $8426, $22 633 and $69 412 for females. Conclusions Overall, health care costs for patients with Crohn’s disease increased with disease severity. Although the probabilities of transitioning from other health states to the severe–fulminant disease state were low, the cost/QALY was high.     

Meta‐analysis: pre‐operative infliximab treatment and short‐term post‐operative complications in patients with ulcerative colitis

Aliment Pharmacol Ther 31 , 486–492

Summary

Background Infliximab was approved for use in ulcerative colitis in recent years. It has been debated if infliximab increases the risk of post‐operative complications in patients with ulcerative colitis. Aim To perform a meta‐analysis that examines the relationship between preoperative infliximab treatment and short‐term post‐operative complications in patients with ulcerative colitis. Methods We searched the PubMed and MEDLINE databases to identify observational studies on the impact of pre‐operative infliximab use on short‐term post‐operative complications in ulcerative colitis. Infectious complications mainly included wound infection, sepsis and abscess, whereas non‐infectious complications included intestinal obstruction, thromboembolism and gastrointestinal haemorrhage. Pooled odds ratios (ORs) were calculated for each relationship. Results A total of 5 studies and 706 patients were included in our meta‐analysis. Overall, we did not find a strong association between pre‐operative treatment of infliximab and short‐term infectious [OR 2.24, 95% confidence interval (CI) 0.63–7.95] or non‐infectious (OR 0.85, 95% CI 0.50–1.45) post‐operative complications in ulcerative colitis patients. On the contrary, we discovered that pre‐operative infliximab use increased short‐term total post‐operative complications (OR 1.80, 95% CI 1.12–2.87). Conclusions Pre‐operative infliximab use increased the risk of short‐term post‐operative complications. Subgroup analysis is underpowered to assess the nature of these complications but shows a trend towards increased post‐operative infection.     

The immunoregulatory cytokine interleukin‐10—a therapy for Crohn’s disease?

The gastrointestinal tract serves as a barrier between the host and the vast array of foreign antigens that are contained within its lumen. The mucosal immune system must balance two opposing functions: to mount an immune response to pathogens, whilst maintaining tolerance to antigens derived from commensal bacteria and food. This balance is regulated by both cellular interactions and the release of soluble mediators called cytokines. Diseases such as ulcerative colitis and Crohn's disease are characterized by alterations in the balance of pro-inflammatory and regulatory cytokines. Interleukin-10 is a regulatory cytokine which inhibits both antigen presentation and subsequent pro-inflammatory cytokine release. In addition, there is evidence that it promotes the formation of antigen-specific regulatory T-cell clones. The pivotal role played by interleukin-10 within the mucosal immune system is demonstrated both by the chronic ileocolitis that develops in gene-targeted interleukin-10 knock-out mice, and by its therapeutic efficacy in several animal models of colitis. However, trials of daily systemic interleukin-10 administration in patients with Crohn's disease have reported only a modest clinical response. Advances in the analysis of functional polymorphisms in the interleukin-10 gene may allow therapy to be targeted to patients who will respond. Finally, therapeutic strategies utilizing gene therapy may enhance mucosal delivery and increase therapeutic response.     

Review article: anti‐fibrotic agents for the treatment of Crohn’s disease – lessons learnt from other diseases

Background The current therapies for Crohn’s disease (CD) are mainly focused on blockade of inflammation. Fibrosis remains one of the major complications of CD often leading to surgery, affecting patients’ quality‐of‐life. Aim To summarize the published data regarding the potential anti‐fibrotic role of drugs commonly used in CD and the most effective anti‐fibrotic drugs used in other diseases evaluating their potential use to treat intestinal fibrosis in CD. Methods A literature search was performed in the PubMed, Medline, Cochrane and EMBASE databases, considering in vitro, animal and human studies on fibrosis in inflammatory bowel disease and other similar chronic pathologies. Results Treatment of fibrosis in CD is limited to surgery or endoscopic dilatation, although some of the drugs currently used may have anti‐fibrotic activity. In other diseases, anti‐fibrotic agents are already used or are in preclinical or clinical trials. ACE inhibitors, Angiotensin Receptor Blockers, and HMG‐CoA inhibitors merit further investigation in CD because of their role in preventing fibrosis in cardiovascular and renal diseases. Conclusions Anti‐fibrotic drugs are under evaluation or already used in clinical practice in other chronic inflammatory diseases. In CD, there is a great need for investigation into agents that may prevent, reduce or reverse intestinal fibrosis. Aliment Pharmacol Ther 31 , 189–201