Mesalazine vanishing time from rectal mucosa following its topical administration.

To investigate how long and how much Mesalazine (M) is available inside the rectal mucosa following its topical instillation, in patients (pts) with Ulcerative Colitis (UC). Two rectal biopsies for M concentration were obtained from 45 UC pts in clinical remission and on oral M treatment (OT), before a 4g enema randomly given to consentient pts every day (Group A, 15 pts), every 2 days (Group B, 15 pts) and every 3 days (Group C, 15 pts). Two additional biopsies were taken 1, 2 and 3 days after the last enema in group A, B and C respectively, at least 10 days later. All biopsies were immediately frozen at -80°C for later assay by means of high-performance light chromatography (HPLC). Data were analyzed using Student's t-test. Mean values±standard deviation of M mucosal concentration (ng/mg of tissue) were 1.32±1.41, 56.1±39.2, 9.65±6.60, and 6.39±5.03 in pts receiving OT alone, groups A, B and C, respectively. Values in Group A were statistically higher (p<0.001) than those in Groups B and C while no differences were found between Groups B and C. Values of OT were lower than groups A, B and C. M mucosal concentration rapidly decreases 2 days after a 4g enema, but after three days is still higher than OT alone. These results may provide data which would be useful to plan topical therapy and improve adherence to treatment.

Clinical trial: ulcerative colitis maintenance treatment with 5-ASA: a 1-year, randomized multicentre study comparing MMX with Asacol.

BACKGROUND: 5-ASA-MMX (1.2 g/tablet) is a 5-aminosalicylic acid formulation, designed for once-daily dosing in the treatment of ulcerative colitis. AIM: To evaluate the efficacy and safety of 5-ASA-MMX (2.4 g/day, once daily), compared with Asacol (2.4 g/day, twice daily) in the maintenance of left-sided UC, through a double-blind, double-dummy, parallel-group, randomized, comparator study. METHODS: In all, 331 patients with UC were randomized to receive either 5-ASA-MMX 2.4 g/day, once daily, or Asacol 2.4 g/day, twice daily, for 12 months. All patients were in remission for >or=1 month prior to the trial, with >or=1 documented relapse in the previous year. The co-primary endpoints of this study were the proportion of patients in clinical, and clinical and endoscopic remission following 12 months' treatment. RESULTS: In the intent-to-treat population, excluding those with major protocol deviations, 68.0 and 65.9% patients in the 5-ASA-MMX and Asacol groups, respectively, were in clinical remission (P = 0.69), and 60.9 and 61.7% of patients, respectively, were in clinical and endoscopic remission (P = 0.89). Diary card data revealed statistically significant treatment differences favouring 5-ASA-MMX. Both treatments were similarly tolerated. CONCLUSIONS: Once-daily 5-ASA-MMX is similarly effective with a comparable safety profile to Asacol administered twice daily, for the maintenance treatment of ulcerative colitis.

Smad3 loss confers resistance to the development of trinitrobenzene sulfonic acid-induced colorectal fibrosis.

BACKGROUND: Transforming growth factor-beta (TGF-beta)/Smad3 signalling plays a central role in tissue fibrogenesis, acting as a potent stimulus of extracellular matrix (ECM) protein accumulation. The aim of this study was to evaluate the potential role of Smad3 in the pathogenesis of colonic fibrosis induced by trinitrobenzene sulfonic acid (TNBS) in Smad3 null mice. MATERIALS AND METHODS: Chronic colitis-associated fibrosis was induced in 15 Smad3 null and 13 wild-type mice by intra-rectal administration of TNBS. Each mouse received an incremental dose of TNBS (0.5-1.0 mg per week) over a 6-week period. The colon was excised for macroscopic examination and histological, morphometric and immunohistochemical analyses. For immunohistochemistry, alpha-smooth muscle actin (alpha-SMA), collagen types I-III, TGF-beta1, connective tissue growth factor (CTGF), Smad3, Smad7, and CD3 antibodies were used. RESULTS: At macroscopic examination, the colon of Smad3 wild-type mice appeared significantly harder, thicker and shorter than that of the Smad3 null mice. Of the wild-type mice, 50% presented colonic adhesions and strictures. Histological and morphometric evaluation revealed a significantly higher degree of colonic fibrosis and accumulation of collagen in the Smad3 wild-type compared to null mice, whereas the degree of colonic inflammation did not differ between the two groups of mice. Immunohistochemical evaluation showed a marked increase in CTGF, collagen I-III, TGF-beta and Smad3 staining in the colon of Smad3 wild-type compared to null mice, whereas Smad7 was increased only in null mice. CONCLUSIONS: These results indicate that Smad3 loss confers resistance to the development of TNBS-induced colonic fibrosis. The reduced fibrotic response appears to be due to a reduction in fibrogenic mesenchymal cell activation and ECM production and accumulation. Smad3 could be a novel target for potential treatment of intestinal fibrosis, especially in inflammatory bowel disease.

Clinical course of Crohn's disease first diagnosed at surgery for acute abdomen.

BACKGROUND: The severity of clinical activity of Crohn's disease is high during the first year after diagnosis and decreases thereafter. Approximately 50% of patients require steroids and immunosuppressants and 75% need surgery during their lifetime. The clinical course of patients with Crohn's disease first diagnosed at surgery has never been investigated. AIM: To assess the clinical course of Crohn's disease first diagnosed at surgery for acute abdomen and to evaluate the need for medical and surgical treatment in this subset of patients. PATIENTS AND METHODS: Hospital clinical records of 490 consecutive Crohn's disease patients were reviewed. Patients were classified according to the Vienna criteria. Sex, extraintestinal manifestations, family history of inflammatory bowel diseases, appendectomy, smoking habit and medical/surgical treatments performed during the follow-up period were assessed. STATISTICAL ANALYSIS: Kaplan-Meier survival method and Cox proportional hazards regression model. RESULTS: Of the 490 Crohn's disease patients, 115 had diagnosis of Crohn's disease at surgery for acute abdomen (Group A) and 375 by conventional clinical, radiological, endoscopic and histologic criteria (Group B). Patients in Group A showed a low risk of further surgery (Log Rank test p<0.001) and a longer time interval between diagnosis and first operation compared to Group B (10.8 years vs. 5.8 years, p<0.01, respectively). Furthermore, patients in Group A used less steroids and immunosuppressants (OR 0.3, p<0.0001; OR 0.6, p<0.004, respectively). CONCLUSIONS: Crohn's disease patients first diagnosed at surgery for acute abdomen showed a low risk for reintervention and less use of steroids and immunosuppressants during follow-up than those not operated upon at diagnosis. Early surgery may represent a valid approach in the initial management of patients with Crohn's disease, at least in the subset of patients with ileal and complicated disease.

The dyspeptic macrophage 30 years later: an update in the pathogenesis of Crohn's disease.

Alterations in autophagy leading to a defective intracellular response to low-level invasive bacteria are considered a major recent advance in the pathogenesis of Crohn's disease. A genome-wide association study has shown an association of Crohn's disease with the autophagy related 16-like 1 gene. A second autophagy gene, the immunity-related Guanosine triphosfatase, has also been found to be significantly associated with Crohn's disease. The enteric flora of Crohn's disease patients includes, more commonly than controls, strains of adherent/invasive E. coli. The high level of adherent/invasive E. coli colonizing the intestinal mucosa of patients with Crohn's disease strongly suggests that it may play an important role in the aetiopathogenesis of the disease. E. coli strains are able to cross the mucosal barrier, survive within macrophages and induce the secretion of TNFalpha and the formation of granuloma. Recently it has been clearly shown that Crohn's disease patients have a defective mucosal macrophage killing activity resulting in increased exposure to commensal bacteria and activation of T cells. However, the hypothesis of macrophages dysfunction in the pathogenesis of Crohn's disease was already suggested in 1977 by M. Ward, who introduced the concept of the "dyspeptic macrophage", consisting of an inability to degrade a variety of phagocytosed normal gut dietary and microbial luminal constituents. Defective autophagy and dyspeptic macrophages seems therefore indicate the same pathogenetic mechanism. What is really new is the demonstration that this impaired macrophage function is genetically determined.

Long-term prevention of post-operative recurrence in Crohn's disease cannot be affected by mesalazine.

BACKGROUND: Prevention of post-operative recurrence has a central role in the management of Crohn's Disease (CD). Many drugs have been evaluated in prospective randomised controlled trials (RCTs) but the results are disappointing. Mesalazine, the drug more extensively investigated, has been shown to be effective for preventing recurrence in the short-term; however, the overall benefit is small and no data are available on the long-term effectiveness. AIM: To compare the long-term occurrence of post-operative recurrence in patients who received regular prophylactic treatment with mesalazine with patients who did not receive prophylaxis after the first radical resection for ileo-caecal CD. PATIENTS AND METHODS: The records of 216 patients with ileo-caecal CD at their first resection were reviewed: 146 patients (67.6%) received post-operative prophylaxis with mesalazine while 70 patients (32.4%) received no prophylaxis. Allocation of patients in the two groups was determined by patients' preferences and by different policies in the post-operative prophylactic approach. The mean follow-up after surgery was 153.7 months (range 12-544). The co-primary endpoints were post-operative clinical and surgical recurrence. STATISTICAL ANALYSIS: Kaplan-Meier survival method, Chi-square, Student t-test. RESULTS: The two groups were comparable with regard to gender, age at surgery, smoking habits, pattern of CD (perforating/not perforating), and disease duration before surgery. One year after surgery, a small, not statistically significant, risk reduction in clinical recurrence was observed in mesalazine treated group (-7.6%; 95% CI -18.0% to 2.8%). Within 10 years after surgery, the cumulative probability of clinical recurrence and surgical recurrence were similar in the two groups (Log Rank test p=0.9 and p=0.1 respectively). CONCLUSION: Mesalazine prophylaxis is not effective for preventing the long-term post-operative recurrence in ileo-caecal Crohn's disease.

Prevention of colonic fibrosis by Boswellia and Scutellaria extracts in rats with colitis induced by 2,4,5-trinitrobenzene sulphonic acid.

BACKGROUND: Currently, no effective preventive measures or medical therapies are available for intestinal fibrosis and, thus, surgery remains the only available strategy in the management of fibrostenotic enteropathies, especially Crohn's disease. The aim of this study was to evaluate the efficacy of a combined therapy of anti-inflammatory Boswellia and antifibrotic Scutellaria extracts on the development of colonic fibrosis in rats. MATERIALS AND METHODS: Chronic colonic inflammation-associated fibrosis was induced in rats by intracolonic administration of 2,4,5-trinitrobenzene sulphonic acid (TNBS). Sixty-four healthy male Sprague-Dawley rats were assigned to five groups: 8 controls, 14 TNBS, 14 TNBS orally treated with Boswellia extracts (50 mg kg(-1) day(-1)), 14 TNBS orally treated with Scutellaria extracts (150 mg kg(-1) day(-1)), and 14 TNBS orally treated with both Boswellia (50 mg kg(-1) day(-1)) and Scutellaria extracts (150 mg kg(-1) day(-1)). The colon was removed after 21 days of treatment and assessed by macroscopic, histological, morphometric and immunohistochemical analyses. For immunohistochemical analysis, alpha-smooth muscle actin (alpha-SMA), collagen types I-III, connective tissue growth factor (CTGF), transforming growth factor-beta1 (TGF-beta1), Smad3, Smad7 and CD3 antibodies were used. RESULTS: Combined oral administration of Boswellia and Scutellaria significantly improved the course and macroscopic findings of TNBS-induced chronic colitis assessed by disease activity index, colon weight, length, adhesions, strictures, dilatation, thickness, oedema, ulcerations and extension of damage. The histological severity of the colonic fibrosis was also notably improved by the treatment and associated with a significant reduction in the colonic expression of alpha-SMA, collagen I-III, CTGF, TGF-beta1, Smad3, and Smad7. CONCLUSIONS: These data demonstrate that the prophylactic administration of anti-inflammatory Boswellia and antifibrotic Scutellaria extracts is effective in preventing colonic fibrosis in TNBS-induced colitis. Their antifibrotic mechanism of action seems to be mediated by the inhibition of TGF-beta1/Smad3 pathway.

Colectomy rate in acute severe ulcerative colitis in the infliximab era.

BACKGROUND: Severe ulcerative colitis is a potentially life-threatening condition. Due to advances in medical therapy, the mortality rate has dropped to <2% over the past 30 years, but the colectomy rate reaches 30%. Recently, infliximab has been shown to be effective as rescue therapy but little is known about long-term benefits. AIM: To evaluate short-and long-term colectomy rates for severe ulcerative colitis in the era of biological treatment and to identify predictive factors of long-term colectomy. PATIENTS AND METHODS: From 2001 to 2006 all in-patients with severe ulcerative colitis, according to Truelove and Witts criteria, were retrospectively reviewed. All patients had received intravenous steroid treatment; infliximab (5 mg/kg at 0, 2 and 6 weeks) was used as rescue therapy in steroid-refractory patients; colectomy was performed in patients who deteriorated whilst on steroid treatment or failed to respond to infliximab. RESULTS: Of the 314 ulcerative colitis patients hospitalized during the study period, 52 (16.5%) met the criteria of severe ulcerative colitis. After median 7 days (range 4-15) on intravenous steroids, 37/52 (71%) patients showed a clinical response, while 15/52 (29%) were steroid-refractory. Of these, four underwent urgent colectomy and 11 received infliximab. A clinical response was observed in all infliximab-treated patients. In the long-term, another six patients underwent elective colectomy. The overall colectomy rate, following the acute attack, was 19%; the cumulative probability of a course without colectomy was 90%, 86%, 84%, 81%, after 6, 12, 18 and 24 months, respectively. No deaths occurred. The long-term colectomy risk was comparable in patients treated with infliximab and in steroid-responsive patients (18% vs. 11% respectively; OR 1.9; 95% CI 0.26-14.5). No predictive factors of colectomy, in the long-term, were identified. CONCLUSIONS: Surgery continues to play an important role in acute severe ulcerative colitis. Infliximab can avoid urgent colectomy in steroid-refractory patients but the risk of elective colectomy, in the long-term, is not modified.

Recent advances in the management of Crohn's disease.

In the last 10 years many advances have been achieved in the treatment of patients with Crohn's disease, particularly in the field of biological agents. Infliximab, a tumour necrosis factor alpha antagonist, has been recently added to the therapeutic armamentarium for Crohn's disease and has greatly improved our treatment options. Infliximab has demonstrated efficacy in the induction and maintenance of remission in luminal and fistulizing Crohn's disease both in adults and children. However, the potential development of autoantibodies and the risk of serious adverse events limit the possibility of a wider use of infliximab. Searching for less immunogenicity and higher effectiveness in the last years a number of biological agents have been developed. Adalimumab, a fully human monoclonal antibody anti tumour necrosis factor alpha, has resulted effective and safe in patients with Crohn's disease, both naive and refractory to infliximab, presenting also the advantage of subcutaneous way of administration. Natalizumab also showed promising results in terms of efficacy but its safety is still under investigation. To date no particular advances have been recently appeared in the literature concerning conventional immunosuppressive drugs. Surgery remains a valid resort for refractory patients. Autologous stem cell transplantation represents a new hope as rescue treatment for patients with severe refractory Crohn's disease.

The association of MYO9B gene in Italian patients with inflammatory bowel diseases.

BACKGROUND: Variants of myosin IXB (MYO9B) gene, encoding for a motor protein implicated in epithelial permeability, have been recently associated with inflammatory bowel disease. AIMS: To investigate the contribution of three polymorphisms of MYO9B gene for predisposition to Crohn's disease and ulcerative colitis, their association with clinical phenotypes, particularly intestinal permeability, and possible interaction with the CARD15 gene. METHODS: 549 Crohn's disease patients, 658 ulcerative colitis patients and 674 controls were genotyped for the rs962917, rs1545620 and rs2305764 single nucleotide polymorphisms. RESULTS: Highly significant genotypic association with Crohn's disease and ulcerative colitis was shown for all three single nucleotide polymorphisms, with odds ratio ranging from 1.5 to 1.7 (P-value: <0.01 to <0.002). A significant difference in allele frequencies was also observed in inflammatory bowel disease patients, with the single most significant association for rs1545620, detected in 47% of Crohn's disease, 47% of ulcerative colitis patients and 42% of controls (P < 0.005). No association with specific sub-phenotypes was found, with the exception of a trend towards an abnormal intestinal permeability (P = 0.043) in Crohn's disease carrying the rs1545620 risk allele. CONCLUSIONS: Our findings confirm the association between the MYO9B polymorphisms and susceptibility to both ulcerative colitis and Crohn's disease, with a weak influence on sub-phenotypic expression.

Early versus late surgery for ileo-caecal Crohn's disease.

BACKGROUND: Surgical resection is almost inevitable in Crohn's disease. Surgery is usually performed for refractory or complicated disease: no studies appear to have been carried out, so far, to evaluate the potential benefits of performing surgery early in the course of the disease. AIM: To compare the long-term course of Crohn's disease following ileo-caecal resection performed at the time of diagnosis (early surgery) or during the course of the disease (late surgery). Patients and methods Overall 207 patients with ileo-caecal Crohn's disease at their first resection were reviewed: 83 patients underwent surgery at the time of diagnosis (early surgery), while 124 underwent surgery 54.2 months (range 1-438) after diagnosis (late surgery). The mean follow-up after surgery was 147 months (range 12-534). The primary endpoint was clinical recurrence, defined as need for corticosteroids for symptomatic disease in the presence of endoscopic and/or radiologic recurrence. Secondary endpoints were need for immunosuppressants and surgical recurrence. STATISTICAL ANALYSIS: Kaplan-Meier survival method and Cox proportional hazards regression model. RESULTS: Within 10 years after surgery, the cumulative probability of clinical recurrence was significantly lower in the early surgery group (Log Rank test P = 0.01). A trend was observed regarding the need for immunosuppressants (P = 0.05). No difference was observed regarding surgical recurrence. At multivariate analysis, early surgery was the only independent variable associated with a reduced risk of clinical recurrence (Hazard ratio, HR = 0.57; 95% CI 0.35 to 0.92, P = 0.02), but not with need for immunosuppressants and surgical recurrence (HR = 0.51; 95% CI 0.20 to 1.30, P = 0.15; HR = 0.66; 95% CI 0.33 to 1.35, P = 0.25, respectively). CONCLUSION: Early surgery prolongs clinical remission compared to surgery performed during the course of the disease, but the natural history of disease is not modified.

Use of a 99mTc labeled anti-TNFalpha monoclonal antibody in Crohn's disease: in vitro and in vivo studies.

AIM: Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by a cellular-mediated immune response driven by cytokines secreted mainly by T helper 1 cells (Th1). In active phases of the disease, an increased production and release of tumor necrosis factor a (TNFalpha) by macrophages and monocytes of the lamina propria has been described. The aim of this study was to detect the presence of TNFalpha within the gut mucosa in patients with active CD by using (99m)Tc-labelled chimeric human/mouse monoclonal antibody anti-TNFalpha (Infliximab, Remicade). METHODS: Infliximab has been labeled with (99m)Tc after reduction of disulfide bound by 2-ME method. In vitro binding assay and biodistribution in animal of [(99m)Tc]Infliximab has been performed to evaluate the retention of its biological activity. Ten patients with active CD refractory to conventional medical therapies were studied. Images of the abdomen were acquired at 6 to 20 h after i.v. injection of about 10 mCi of [(99m)Tc]Infliximab and a week later, all patients were also studied with [(99m)Tc]HMPAO-labeled autologous white blood cells (WBC). RESULTS: A product with high labeling efficiency (>95%) and stability has been obtained. In vitro tests with stimulated T-cells expressing TNFalphalpha indicated that [(99m)Tc] Infliximab retains its binding activity to cell bound TNFalpha as compared to unlabelled Infliximab. The degree of [(99m)Tc]Infliximab uptake by the inflamed bowel evaluated at 20 h postinjection was much less than that seen with labeled WBC and with a different distribution. Three of these patients received anti-TNFalpha (Infliximab) for therapeutic purposes with good clinical results despite the scintigraphy with (99m)Tc-Infliximab was negative in 2 of them. CONCLUSION: Scintigraphy with [(99m)Tc]Infliximab shows the presence of little TNFalpha in the affected bowel of patients with active CD. Therefore, the clinical benefit that patients have from Infliximab therapy is unlikely the consequence of a local a reduction of TNFalpha and the mechanism of action of Infliximab, in therapeutic doses, deserves further investigations.

Mucosal features and granulocyte-monocyte-apheresis in steroid-dependent/refractory ulcerative colitis.

BACKGROUND: Mucosa-infiltrated granulocyte neutrophils are an early characteristic of inflammation and the main histological feature of active ulcerative colitis. Mucosal healing has recently been indicated as an important tool in the evaluation of response to treatment. While several studies have stressed the efficacy of granulocyte-monocyte-apheresis in inducing clinical remission in active ulcerative colitis, few data are available on mucosal features. AIM: Aim of this study was to assess the effects of granulocyte-monocyte-apheresis on clinical and mucosal features in patients with ulcerative colitis, dependent upon or refractory to steroids. MATERIAL AND METHODS: From April 2004 to April 2005, 12 patients (5 females, 7 males, mean age 49 years, range 33-71 years), with mild-moderate ulcerative colitis (six left colitis, six pancolitis) dependent/refractory upon steroids were enrolled. Each patient was treated for a 5-week period with five cycles of granulocyte-monocyte-apheresis. Patients were evaluated at baseline and 1 week after the last apheresis by means of Global Physician Assessment, quality of life features, laboratory tests (erythrocyte sedimentation rate, CRP, full blood count, faecal calprotectine), endoscopy and histology. RESULTS: At week 6 of follow-up, complete mucosal healing was observed in 3 out of 12 patients, partial mucosal healing in 8 patients and no change in 1 patient. Clinical response was complete in 8 out of 12 patients. CONCLUSIONS: These data suggest that granulocyte-monocyte-apheresis induces an improvement both in clinical and mucosal lesions in steroid-dependent/refractory ulcerative colitis. Of note, the reduction in granulocyte infiltration and the improvement in mucosal lesions are accompanied by a reduction in faecal calprotectine.

European evidence based consensus on the diagnosis and management of Crohn's disease: special situations.

This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease.

Two synchronous adenocarcinomas of the small bowel in a patient with undiagnosed Crohn's disease of the terminal ileum.

A small but significant excess of deaths for tumors of the digestive system has been described in Crohn's disease. In a study analyzing all cancers of the small intestine within a defined population, Crohn's disease was the major underlying factor for cancer of the small intestine. Areas of the small intestine containing strictures are unusually prone to malignant transformation. We report the rare case of a patient in whom surgery for intestinal occlusion disclosed Crohn's disease of the distal ileum complicated by two adenocarcinomas arising within distinct areas of the inflamed bowel.

Seasonal variations in onset of symptoms in Crohn's disease.

BACKGROUND: Seasonal variations in onset of symptoms have been reported in ulcerative colitis but not in Crohn's disease. AIM.: To investigate whether our inflammatory bowel diseases patients presented seasonal variations in onset of symptoms. PATIENTS AND METHODS: Patients with a diagnosis of inflammatory bowel diseases established between 1995 and May 2004, and consecutively observed from June 2003 to May 2004, were included in the study. Onset of symptoms (year, season and month) was recorded. Expected onsets with a uniform distribution during the year were calculated and compared to observed onsets. STATISTICAL ANALYSIS: chi-square test, odds ratio (95% confidence interval). RESULTS: Overall 425 inflammatory bowel diseases patients were enrolled. Onset of symptoms (year and season) was established in 353/425 patients (83%; 150 Crohn's disease; 203 ulcerative colitis). Onset of symptoms in inflammatory bowel diseases patients as a whole occurred more frequently in spring-summer compared to autumn-winter (odds ratio 1.39; 95% confidence interval 1.03-1.87; p<0.03). This variation was observed in Crohn's disease (odds ratio 1.59; 95% confidence interval 1.00-2.51; p<0.05) and a similar trend, although not significant, was observed in ulcerative colitis (odds ratio 1.27; 95% confidence interval 0.86-1.88; p=0.27). CONCLUSIONS: These data indicate that onset of Crohn's disease symptoms occurred more frequently during spring-summer. A similar trend was observed in ulcerative colitis. Environmental factors, such as associated infections, smoking, use of drugs and seasonal changes in immune function may be responsible for triggering the clinical onset of inflammatory bowel diseases.

Early or late guided missile in the treatment of Crohn's disease?

Over the last few years, much light has been shed on the pathogenesis of Crohn's disease. Further knowledge in this field has provided a firm basis not only in the understanding of current treatment but also for the development of new therapeutic strategies. Aim of these new agents is primarily to selectively interact with the key processes of intestinal inflammation. At present, only anti-tumour necrosis factor-alpha antibodies namely infliximab, is licensed for clinical practice but it is feasible to foresee that, in the near future, a larger range of these agents will become available. Herein, the most promising biological agents in the treatment of Crohn's disease are outlined, which patients would benefit from these agents and when they should be administered. Attention is focused on the early (top-down) or late (step-up) use of biological agents, which for their very targeted mechanism of action may be compared to guided missiles. As yet, early use of biological agents remains to be supported by convincing evidence, nevertheless it may be advocated as first-line therapy for newly diagnosed severe Crohn's disease patients, both adults and children.