Different Profile of Efficacy of Thiopurines in Ulcerative Colitis and Crohn's Disease.

BACKGROUND: Thiopurines are effective drugs in treating ulcerative colitis (UC) and Crohn's disease (CD) even if studies that specifically investigate these drugs' profile of efficacy in UC compared with CD are scarce. Our aim was to compare the profile of efficacy of thiopurines in patients with UC and CD. METHODS: We perfomed a longitudinal observational study evaluating steroid-free clinical remission (CR) and mucosal healing (MH) in all patients with UC and CD who would complete 2 years of maintenance treatment with thiopurines. In patients with UC, CR and MH were assessed before starting treatment and 2 years later using the Mayo score (CR = Mayo score <2; MH = Mayo subscore ≤1). In patients with CD, CR and MH were assessed at the same time points using the Crohn's disease activity index (CR = Crohn's disease activity index < 150) and the Simplified Endoscopic Score for Crohn's Disease (MH = Simplified Endoscopic Score for Crohn's Disease < 2). The efficacy of thiopurines was assessed through intention-to-treat and per-protocol analyses. RESULTS: The study included 205 steroid-dependent patients (104 UC; 101 CD), 140 of whom (70 UC; 70 CD) completed the 2-year observation period. Steroid-free CR was recorded in 43 patients with UC and 37 with CD (intention-to-treat: 41% versus 36%; P = 0.6; per-protocol: 61% versus 53%; P = 0.4); MH was obtained in 38 patients with UC and 17 with CD (intention-to-treat: 36% versus 16%; P < 0.01; odds ratio, 2.9; per-protocol: 54% versus 25%; P < 0.01; odds ratio, 3.7). CONCLUSIONS: Thiopurines are effective in maintaining steroid-free CR in both UC and CD although they show a better profile of efficacy in terms of MH in cases of UC.

Transmural healing evaluated by bowel sonography in patients with Crohn's disease on maintenance treatment with biologics.

BACKGROUND: Both thiopurines and anti-tumor necrosis factor (TNF) α agents are effective for treating Crohn's disease (CD) as they can induce clinical remission (CR) and mucosal healing (MH) in most patients. Nevertheless, data on transmural healing (TH) induced by thiopurines and anti-TNF-α agents are still lacking. This study aimed to explore the rate of TH evaluated by bowel sonography in patients with CD treated with biologics and immunosuppressors and its correlation with CR and MH. METHODS: We performed an observational longitudinal study evaluating TH, CR, and MH in all patients with CD attending our clinic who would complete 2 years of maintenance treatment with biologics or thiopurines. CR and MH were assessed in accordance with current literature, whereas TH was recorded using bowel sonography. All patients underwent endoscopy and bowel sonography before starting treatment and 2 years later. RESULTS: The study included 66 patients with CD treated with biologics and 67 patients receiving thiopurines. Finally, TH was present in 17 patients on biologics and only 3 patients treated with thiopurines (25% versus 4%; P < 0.01; odds ratio = 6.2). CR was achieved in 37 patients on biologics and in 34 patients on thiopurines (59.7% versus 53%; P = not significant), whereas MH was more frequent in patients treated with anti-TNF-α agents even though without statistical significance (38% versus 25%; P = not significant). CONCLUSIONS: TH can be achieved in approximately 25% of patients with CD treated with anti-TNF-α agents and significantly correlates with MH. Further studies are needed to define the potential role of TH as long-term prognostic factor.

Noninvasive diagnosis of small bowel Crohn's disease: direct comparison of bowel sonography and magnetic resonance enterography.

BACKGROUND: The diagnosis of small bowel Crohn's disease (CD) is performed by ileocolonoscopy, whereas the assessment of its extension can be achieved by radiologic studies or, noninvasively, by magnetic resonance (MR) enterography and bowel sonography (BS). However, few comparative studies exist directly comparing the diagnostic accuracy of BS and MRI. The aim of this study was to evaluate the diagnostic accuracy of BS and MRI for the diagnosis of small bowel CD. METHODS: We prospectively performed a noninferiority diagnostic study including 234 consecutive subjects with suspected small bowel CD. All patients underwent IC (used as gold standard for diagnosis), BS, and MR enterography performed in random order by physicians who were blinded about the results. RESULTS: The diagnosis of small bowel CD was made in 120 of 249 subjects (48%). Sensitivity, specificity, positive predictive value, and negative predictive value for CD diagnosis were 94%, 97%, 97%, and 94% for BS and 96%, 94%, 94%, and 96% for MR enterography, respectively. BS was less accurate than MR enterography in defining CD extension (r = 0.69), whereas the concordance in terms of CD location between the 2 procedures was high (k = 0.81). Also, MRI showed a fair concordance with BS about strictures (k = 0.82) and abscesses (k = 0.88), with better detection of enteroenteric fistulas (k = 0.67). CONCLUSIONS: BS and MR enterography are 2 accurate procedures for the diagnosis of small bowel CD, although MR seems to be more sensitive in defining its extension. BS could be used to select the patients for subsequent MRI examination.

Risk factors for inflammatory bowel diseases according to the "hygiene hypothesis": a case-control, multi-centre, prospective study in Southern Italy.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD) of unknown aetiology. The 'hygiene hypothesis' (HH) suggests that several hygiene-related factors may have contributed to the increased incidence of IBD. The aim of the study was to evaluate risk factors for IBD related to HH in a cohort of IBD patients from the south of Italy. METHODS: We prospectively performed a one-year, questionnaire-based, case-control, multi-centre study focusing on the principal risk factors for IBD according to HH. We investigated the main surrogate markers of HH (helmintic infections and antibiotics in childhood; breastfeeding; family size/sibship;urban upbringing; personal and domestic hygiene in childhood) in UC and CD patients, in comparison with a control group of healthy subjects. In addition, the traditional risk factors for IBD were also recorded. RESULTS: The study population included 527 cases of UC, 468 CD and 562 controls. None of the surrogate risk factors of HH was significantly associated with IBD. On the contrary, the traditional risk factors confirmed their statistical significance in this IBD population. Familial aggregation: OR 4.07 for UC; OR 4.83 for CD; smoking: OR 0.38 for UC; OR 1.40 for CD; appendectomy: OR 0.28 for UC; OR 1.61 for CD. CONCLUSION: Even though risk factors associated to the HH have been proposed as a possible explanation for the increasing calendar trend of IBD incidence, their role does not appear to be statistically significant. Familial aggregation, smoking habits and appendectomy still remain the main risk factors associated with IBD.

Oral contrast-enhanced sonography for the diagnosis and grading of postsurgical recurrence of Crohn's disease.

BACKGROUND: Postsurgical recurrence (PSR) is very common in patients with Crohn's disease (CD) and previous surgery. Endoscopy is crucial for the diagnosis of PSR, also showing high prognostic value. Bowel sonography (BS) with or without oral contrast enhancement (OCBS) is accurate for CD diagnosis but its role in PSR detection and grading is poorly investigated. The aim was to evaluate the diagnostic accuracy of BS and OCBS for PSR compared to the endoscopical Rutgeerts's grading system. METHODS: We prospectively performed endoscopy, BS, and OCBS in 40 CD patients with previous bowel resection to provide evidence of possible PSR. Endoscopy, BS, and OCBS were executed 1 year after surgery, with PSR diagnosis and grading made in accordance with Rutgeerts. BS and OCBS were considered suggestive for PSR in the presence of bowel wall thickness (BWT) >3 mm. OCBS was performed after ingestion of 750 mL of polyethylene glycol (PEG). Also, a receiver operating characteristic (ROC) curve was constructed in order to define the best cutoff of BWT to discriminate mild from severe PSR (grade 0-2 versus 3-4 of Rutgeerts) for both BS and OCBS. RESULTS: In all, 22 out of the 40 CD showed an endoscopic evidence of PSR (55%). A severe PSR was present in 14 patients (64%). Sensitivity, specificity, and positive and negative predictive values were 77%, 94%, 93%, and 80% for BS, and 82%, 94%, 93%, and 84% for OCBS. On the ROC curve a BWT >5 mm showed sensitivity, specificity, and positive and negative predictive values of 93%, 96%, 88%, and 97% for the diagnosis of severe PSR at BS, while a BWT >4 mm was the best cutoff differentiating the mild from the severe CD recurrence for OCBS, with a sensitivity, specificity, and positive and negative predictive values of 86%, 96%, 97%, and 79%, respectively. CONCLUSIONS: Both BS and OCBS show good sensitivity and high specificity for the diagnosis of PSR in CD, with a BWT >5 mm for BS and BWT >4 mm for OCBS strongly indicative of severe endoscopic PSR. Accordingly, these techniques could replace endoscopy for the diagnosis and grading of PSR in many cases.