Continuous clinical remission with biologics in ulcerative colitis: the 'AURORA' comparison study.

OBJECTIVES: Comparative trials among biological drugs for the treatment of ulcerative colitis (UC) provided conflicting results. After patent expire of infliximab originator, adalimumab, infliximab biosimilar, golimumab and vedolizumab have been approved in Italy.We compared the efficacy of these four biologics in UC according to the concept of continuous clinical remission (CCR). METHODS: In a retrospective, multicentre study, all UC patients treated with adalimumab, infliximab biosimilar, golimumab or vedolizumab between 2014 and 2019 were included. All drugs were compared to each other according to the 1-year CCR rate, defined as Mayo partial score ≤2, with bleeding subscore = 0, without any relapse or optimization with dose escalation, topical treatments or steroid use after first clinical remission. RESULTS: Four-hundred sixteen patients (adalimumab = 90, infliximab biosimilar = 105, golimumab = 79, vedolizumab = 142) were included. CCR was achieved in similar percentages among the groups (33%, 37%, 28%, 37%, respectively). All drugs were equivalent in biologic-naive patients, while vedolizumab was better than a second anti-TNFα in prior anti-TNFα agent failures. No differences were found according to type of adverse events or severe adverse events. CONCLUSIONS: Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year. Changing to vedolizumab is more effective than switching to another anti-TNFα in TNFα failures.

High frequency of intestinal TH17 cells correlates with microbiota alterations and disease activity in multiple sclerosis.

T helper 17 (TH17) cells are key players in multiple sclerosis (MS), and studies in animal models demonstrated that effector TH17 cells that trigger brain autoimmunity originate in the intestine. We validate in humans the crucial role of the intestinal environment in promoting TH17 cell expansion in MS patients. We found that increased frequency of TH17 cells correlates with high disease activity and with specific alterations of the gut mucosa-associated microbiota in MS patients. By using 16S ribosomal RNA sequencing, we analyzed the microbiota isolated from small intestinal tissues and found that MS patients with high disease activity and increased intestinal TH17 cell frequency showed a higher Firmicutes/Bacteroidetes ratio, increased relative abundance of Streptococcus, and decreased Prevotella strains compared to healthy controls and MS patients with no disease activity. We demonstrated that the intestinal TH17 cell frequency is inversely related to the relative abundance of Prevotella strains in the human small intestine. Our data demonstrate that brain autoimmunity is associated with specific microbiota modifications and excessive TH17 cell expansion in the human intestine.

Referrals for bowel ultrasound in clinical practice: a survey in 12 nationwide centres in Italy.

BACKGROUND: The value of ultrasound (US) in assessing gastrointestinal diseases is well documented, but its demand in clinical practice is unknown. This survey evaluated the demand for bowel US in Italy. METHODS: Twelve sonographers of the Gastroenterology Section of the Italian Society of Ultrasound participated in a 1-month survey; they compiled a questionnaire assessing total number of patients referred for abdominal US and for gastrointestinal tract US, type of referring physician, indications and results of examinations. RESULTS: The survey included 2424 examinations, 586 of which (24%) investigated the gastrointestinal tract: 280 for signs or symptoms and 268 for follow-up of pre-existing gastrointestinal diseases. Referring physicians were mainly gastroenterologists (78%) and general practitioners (13%). Organic lesions were found or suspected in 292 examinations. CONCLUSIONS: Bowel US is used in Italy in routine practice, mainly by gastroenterologists and general practitioners, both for follow-up of pre-existing diseases and for gastrointestinal complaints.

Hydrosonography of the gastrointestinal tract.

OBJECTIVE: Bowel sonography has become accepted as a useful tool in several gastrointestinal disorders. Filling of the gut with echo-poor liquids has been proposed to achieve a detailed evaluation of the bowel. This article refers to a review made concerning the benefits and limits of hydrosonography of the gastrointestinal tract. CONCLUSION: The use of a luminal contrast agent in bowel sonography may improve results but should be adopted on a case-by-case basis, according to the clinical context and the experience of the sonologist.

Prevalence and clinical significance of sonographic evidence of mesenteric fat alterations in Crohn's disease.

BACKGROUND: Mesenteric adipose tissue hypertrophy is a frequent sonographic finding in Crohn's disease (CD). This study assessed its sonographic prevalence, the correlation with the degree of clinical or biochemical activity of the disease, and its impact on disease outcome in CD patients. METHODS: In all, 185 consecutive CD patients underwent bowel ultrasound to assess the presence of mesenteric fat tissue alteration as well as thickness and echopattern of the bowel wall, site and extent of CD, and presence of stenosis, fistulas, and abscesses. Clinical and biochemical parameters of disease activity were also assessed. Multiple logistic regression analysis was used to identify variables related to mesenteric adipose tissue alteration. RESULTS: Mesenteric adipose tissue alteration, detected in 88 (47.6%) patients, showed a significant correlation both with clinical and biochemical CD activity and with internal fistulas, bowel wall thickness, and length of thickened bowel wall. Logistic regression analysis showed that internal fistulas (odds ratio [OR] = 13.5), thickened bowel wall (OR = 7.6), C-reactive protein (OR = 6.1), CD Activity Index (CDAI) (OR = 3.1), and length of diseased bowel walls (OR = 2.6) were significantly associated with mesenteric adipose tissue alteration. Of the 111 patients with quiescent CD, 22 showed mesenteric adipose tissue hypertrophy. These patients did not show increased risk of relapse compared with quiescent patients without mesenteric fat alteration. CONCLUSIONS: Mesenteric adipose tissue alteration is correlated with biochemical and clinical activity of CD and with internal fistulas and increased bowel wall thickness. In quiescent CD, mesenteric hypertrophy does not appear to be a risk factor of relapse.

Transperineal ultrasound in the detection of perianal and rectovaginal fistulae in Crohn's disease.

OBJECTIVES: Perianal and rectovaginal fistulae are common complications in Crohn's disease. Magnetic resonance imaging (MRI) and endoanal ultrasound are used for imaging perianal fistulae and abscesses, but both methods require expensive equipment and experienced investigators. Transperineal ultrasound may represent another method of detecting perianal complications in Crohn's disease. We investigated Crohn's disease perianal and rectovaginal fistulae using transperineal ultrasound and compared the findings with results of endoanal ultrasound as reference standard. METHODS: A total of 46 patients with Crohn's disease and perianal and/or rectovaginal or anovulvar fistulae underwent, transperineal and endoanal ultrasound, on the same day. Transperineal ultrasound was performed using regular convex and high-resolution linear probes. Endoanal ultrasound was performed using an ultrasound system with a 7 MHz rotating endoanal probe. Fistulae were classified according to Parks' classification in intrasphincteric, transsphincteric, suprasphincteric, and extrasphincteric. Rectovaginal or anovulvar fistulae were described separately. Presence of abscesses was also reported. RESULTS: Fifty-two fistulae (3 intra-sphincteric, 28 transsphincteric, 8 suprasphincteric, 2 extrasphincteric, 9 rectovaginal, and 2 anovulvar) were detected by transperineal ultrasound. Endoanal ultrasound confirmed the correct classification of 45 fistulae (predictive positive value: 86.5%). Of the 53 fistulae detected by endoanal ultrasound, 45 were correctly classified by transperineal ultrasound (sensitivity 84.9%). Transperineal ultrasound showed 10 perianal abscesses: 2 horseshoe, 4 deep, and 4 superficial. Endoanal ultrasound confirmed all horseshoe, 3 deep, and 2 superficial abscesses and did not find further abscesses. CONCLUSIONS: Transperineal ultrasound is a simple, painless, real-time method to detect and classify perianal and rectovaginal fistulae and/or abscesses in Crohn's disease.

Bowel ultrasound in Crohn's disease.

Most published studies have found bowel ultrasound to be a useful tool in the management of Crohn's disease. Indeed, it has been successfully used as the imaging technique of choice in screening patients with clinically suspected Crohn's disease. In these patients, bowel ultrasound, which is well accepted by patients, non-invasive and of low cost, may be the first diagnostic tool employed for young patients and can be used in the preliminary diagnostic work-up prior to further invasive tests. The most important application of bowel ultrasound is, however, in the follow-up of patients already diagnosed with Crohn's disease, in whom it may be useful to assess the site and extent of the lesions and to ensure the early detection of intra-abdominal complications, particularly abscesses and strictures. In this regard, improving the ultrasound assessment of intramural blood flow by means of colour power-Doppler ultrasonography and intravenous contrast agents may help to differentiate fibrotic and inflammatory strictures, and to discriminate inflammatory masses from intra-abdominal abscesses. Despite several attempts to correlate ultrasound findings with clinical and biochemical activity, there are as yet no convincing data on the usefulness of ultrasound in assessing the activity of Crohn's disease. In contrast, preliminary results are in agreement regarding the usefulness of ultrasound in the assessment of postoperative recurrence and in monitoring the outcome of the disease following surgery. In fact, the persistence of a thickened bowel wall or increased high bowel wall thickening at ultrasound following surgery has been identified as an index of early surgical recurrence. How these data may be usefully employed in the management of individuals with Crohn's disease needs to be investigated in further studies.

Azathioprine and mesalamine for prevention of relapse after conservative surgery for Crohn's disease.

BACKGROUND & AIMS: Because the reoperation rate for Crohn's disease is high after resective surgery, use of conservative surgery has increased. Mesalamine was investigated for the prevention of postoperative relapse, with disappointing results. The role of azathioprine in the postoperative setting is unknown. We aimed to compare the efficacy and safety of azathioprine and mesalamine in the prevention of clinical and surgical relapse in patients who have undergone conservative surgery for Crohn's disease. METHODS: In a prospective, open-label, randomized study, 142 patients received azathioprine (2 mg. kg -1. day -1 ) or mesalamine (3 g/day) for 24 months. Clinical relapse was defined as the presence of symptoms with a Crohn's Disease Activity Index score >200 and surgical relapse as the presence of symptoms refractory to medical treatment or complications requiring surgery. RESULTS: After 24 months, the risk of clinical relapse was comparable in the azathioprine and mesalamine groups, both on intention-to-treat (odds ratio [OR], 2.04; 95% confidence interval [CI], 0.89-4.67) and per-protocol analyses (OR, 1.79; 95% CI, 0.80-3.97). No difference was observed with respect to surgical relapse at 24 months between the 2 groups. In a subgroup analysis, azathioprine was more effective than mesalamine in preventing clinical relapse in patients with previous intestinal resections (OR, 4.83; 95% CI, 1.47-15.8). More patients receiving azathioprine withdrew from treatment due to adverse events than those receiving mesalamine (22% vs. 8%; P = 0.04). CONCLUSIONS: While no difference was observed in the efficacy of azathioprine and mesalamine in preventing clinical and surgical relapses after conservative surgery, azathioprine is more effective in those patients who have undergone previous intestinal resection.