Olga Maria Nardone

Long-term combination therapy with infliximab plus azathioprine predicts sustained steroid-free clinical benefit in steroid-dependent ulcerative colitis.

Background:Infliximab (IFX) has demonstrated effectiveness for inducing 12-month steroid-free clinical remission in patients with steroid-dependent ulcerative colitis (UC), but long-term data are lacking. The aim of the study was to describe the long-term outcome of IFX treatment in steroid-dependent UC and investigate if predictors of sustained clinical response and colectomy could be identified. Methods:Consecutive patients with steroid-dependent UC treated with IFX were studied. The coprimary prespecified outcomes were sustained clinical response in patients who achieved clinical remission or response after IFX induction and colectomy-free survival. Secondary analyses were addressed to look for predictors of sustained clinical response and colectomy. Results:After induction, 76% (96/126) of patients achieved clinical benefit. The median duration of follow-up on IFX maintenance therapy was 41.5 months (interquartile range, 26–45). Sixty-four percent (46/96) of patients had sustained clinical response at median follow-up. Colectomy-free survival was 77% at median follow-up. Combination therapy of IFX with thiopurines was an independent predictor of sustained clinical response (P < 0.0001; hazard ratio [HR], 3.98; 95% confidence interval [CI], 1.73–9.14). Independent predictors of colectomy were Mayo endoscopic subscore of 3 at baseline (P = 0.04; HR, 2.77; 95% CI, 1.09–7.05) and high C-reactive protein after induction (P = 0.001; HR, 5.65; 95% CI, 2.03–15.7). Thiopurine naive status (P = 0.025; HR, 0.34; 95% CI, 0.13–0.87) was protective from colectomy. Conclusions:Long-term IFX treatment is effective in inducing sustained clinical response in patients with steroid-dependent UC. Combination therapy is predictive of sustained clinical response in the long-term. Patients with more severe endoscopic lesions at baseline and high C-reactive protein after induction are at higher risk of colectomy. Conversely, thiopurine naive status is protective from colectomy.

Faecal calprotectin assay after induction with anti-Tumour Necrosis Factor α agents in inflammatory bowel disease: Prediction of clinical response and mucosal healing at one year.

BACKGROUND Faecal calprotectin levels correlate with inflammation in inflammatory bowel disease. We evaluated the role of faecal calprotectin after anti-Tumour Necrosis Factor α induction in inflammatory bowel disease patients to predict therapeutic effect at one year. METHODS Faecal calprotectin levels were measured in stools of 63 patients before and after induction of anti-Tumour Necrosis Factor α therapy. Clinical activity, measured by clinical indices, was assessed before and after biologic treatment. Clinical responders after induction were included in the study and colonoscopy was performed before and after one year of treatment to assess mucosal healing. RESULTS 63 patients (44 Crohns disease, 19 ulcerative colitis) were prospectively included (41.2% males, mean age at diagnosis 33 years). A sustained clinical response during the first year was observed in 57% of patients; median faecal calprotectin was 106 μg/g after induction versus 308 μg/g pre-induction (p<0.0001). Post-induction faecal calprotectin was significantly lower in responders versus non-responders (p=0.0002). Post-induction faecal calprotectin had 83% sensitivity and 74% specificity (cut-off ≤ 168 μg/g) for predicting a sustained clinical response at one year (p=0.0001); also, sensitivity was 79% and specificity 57% (cut-off ≤ 121 μg/g) for predicting mucosal healing (p=0.0001). CONCLUSIONS In inflammatory bowel disease faecal calprotectin assay after anti-Tumour Necrosis Factor α induction can be used as a marker to predict sustained clinical response and mucosal healing at one year.

Cross-sectional evaluation of transmural healing in patients with Crohn’s disease on maintenance treatment with anti-TNF alpha agents

BACKGROUND Transmural healing (TH) of Crohns disease (CD) is a still unexplored and interesting outcome correlated to concept of deep remission. AIM To assess the rate of TH in CD patients treated with anti-TNF alpha agents using two cross-sectional procedures: bowel sonography (BS) and magnetic resonance enterography (MRE). METHODS We performed a 2-year observational longitudinal study, evaluating steroid-free clinical remission (CR), mucosal healing (MH), and TH in CD patients who would complete a 2-year treatment period with anti-TNFs. All patients underwent endoscopy, BS, and MRE before and after 2 years of treatment. RESULTS Forty out of 80 CD patients were treated with anti-TNFs for 2 years. CR was achieved in 24 patients (60%) while MH in 14 (35%). Using BS, TH was observed in 10 patients (25%), while using MRE, TH was observed in 9 patients (23%) (k=0.90; P<0.01). A good agreement was observed between MH and TH, both using BS (k=0.63; P<0.01) and MRE (k=0.64; P<0.01). A poor agreement was found between CR and TH, with both BS and MRE (k=0.27 and 0.29, respectively; P<0.01); even though all patients with TH had achieved CR. CONCLUSIONS TH can be achieved in about 25% of CD patients treated with anti-TNFs, as shown by BS and MRE. BS could be used as the first cross-sectional procedure to detect TH.

Bowel Damage in Crohnʼs Disease: Direct Comparison of Ultrasonography-based and Magnetic Resonance-based Lemann Index

Background: The Lémann index (LI), calculated by magnetic resonance (MR) or computed tomography enterography in association with endoscopy, was developed to assess bowel damage (BD) in Crohns disease (CD). Our aim was to investigate the concordance between ultrasonography-based Lèmann index (US-LI) and magnetic resonance–based Lèmann index (MR-LI). Methods: We prospectively evaluated all consecutive patients with CD referred to our IBD Unit. All patients had undergone endoscopy, US and MR within 1 month. US-LI and MR-LI were calculated by scoring previous surgery, location, extension, and intestinal complications. Furthermore, we evaluated the association between LI and: CD duration, Harvey–Bradshaw index, and other relevant clinical features. In accordance with recent literature, an LI >4.8 was considered indicative of BD. Results: Seventy-one patients with CD were examined. About CD location, 36% showed ileal disease (L1), 10% showed colonic CD (L2), whereas 54% had an ileocolonic disease (L3). Moreover, 27% of patients presented a noncomplicated behavior (B1), 45% had almost one stricture (B2), whereas 28% showed penetrating CD (B3). Perianal CD was observed in 16% of subjects, whereas 40% had undergone previous surgery. MR-LI and US-LI were 6.62 (95% confidence interval, 4.2–9.7) and 6.04 (95% confidence interval, 3.6–9.2), respectively (r = 0.90; P < 0.001), with 35 patients (49%) showing an LI indicative of BD. No significant correlation was evident between LI and Harvey–Bradshaw index (P = 0.9), whereas a significant correlation was found between both US-LI/MR-LI and CD duration (P = 0.01). Conclusions: US-LI shows high concordance with MR-LI and could be considered a good option for assessing BD in CD by using a highly available and relatively inexpensive procedure.

Management of difficult-to-treat patients with ulcerative colitis: focus on adalimumab.

The treatment of ulcerative colitis has changed over the last decade, with the introduction of biological drugs. This article reviews the currently available therapies for ulcerative colitis and the specific use of these therapies in the management of patients in different settings, particularly the difficult-to-treat patients. The focus of this review is on adalimumab, which has recently obtained approval by the European Medicines Agency and the US Food and Drug Administration, for use in treating adult patients with moderate-to-severe, active ulcerative colitis, who are refractory, intolerant, or who have contraindications to conventional therapy, including corticosteroids and thiopurines. Since the results emerging from the pivotal trials have been subject to some debate, the aim of this review was to summarize all available data on the use of adalimumab in ulcerative colitis, focusing also on a retrospective series of real-life experiences. Taken together, the current evidence indicates that adalimumab is effective for the treatment of patients with different types of ulcerative colitis, including biologically naïve and difficult-to-treat patients.

Adherence in ulcerative colitis: an overview

Medication adherence is an important challenge while treating chronic illnesses, such as ulcerative colitis (UC), that require a long-term management to induce and maintain clinical remission. This review provides an overview of the role that medication adherence plays in the routine management of UC, with a focus on the results of a recent Italian study reporting the perception of patients with UC regarding adherence to treatment. A literature analysis was conducted on topics, such as measurement of adherence in real practice, causes, risk factors and consequences of non-adherence and strategies, to raise patients’ adherence. Most of the data refer to adherence to 5-aminosalicylic acid, and standard of care for the induction and maintenance of remission in UC. The adherence rate to 5-aminosalicylic acid is low in clinical practice, thus resulting in fivefold higher risk of relapse, likely increased risk of colorectal cancer, reduced quality of life and higher health care costs for in- and outpatient settings. There are various causes affecting non-adherence to therapy: forgetfulness, high cost of drugs, lack of understanding of the drug regimen – which are sometimes due to insufficient explanation by the specialist – anxiety created by possible adverse events, lack of confidence in physicians’ judgment and complex dosing regimen. The last aspect negatively influences adherence to medication both in clinical trial settings and in real-world practice. Regarding this feature, mesalamine in once-daily dosage may be preferable to medications with multiple doses per day because the simplification of treatment regimens improves adherence.

Combined Endoscopic/Sonographic-based Risk Matrix Model for Predicting One-year Risk of Surgery: A Prospective Observational Study of a Tertiary Centre Severe/Refractory Crohn’s Disease Cohort

Background In the management of Crohns disease [CD] patients, having a simple score combining clinical, endoscopic, and imaging features to predict the risk of surgery could help to tailor treatment more effectively. Aims We aimed to prospectively evaluate the 1-year risk factors for surgery in refractory/severe CD and to generate a risk matrix for predicting the probability of surgery at 1 year. Methods CD patients needing a disease re-assessment at our tertiary inflammatory bowel disease [IBD] centre underwent clinical, laboratory, endoscopic, and bowel sonography [BS] examinations within 1 week. The optimal cut-off values in predicting surgery were identified using receiver operating characteristic [ROC] curves for the Simple Endoscopic Score for CD [SES-CD], bowel wall thickness [BWT] at BS, and small bowel CD extension at BS. Binary logistic regression and Cox regression were then carried out. Finally, the probabilities of surgery were calculated for selected baseline levels of covariates and results were arranged in a prediction matrix. Results Of 100 CD patients, 30 underwent surgery within 1 year. SES-CD ≥9 (odds ratio [OR] 15.3; p <0.001], BWT ≥7 mm [OR 15.8; p <0.001], small bowel CD extension at BS ≥33 cm [OR 8.23; p <0.001], and stricturing/penetrating behaviour [OR 4.3; p <0.001] were the only independent factors predictive of surgery at 1 year, based on binary logistic and Cox regressions. Our matrix model combined these risk factors, and the probability of surgery ranged from 0.48% to 87.5% [16 combinations]. Conclusions Our risk matrix combining clinical, endoscopic, and ultrasonographic findings can accurately predict the 1-year risk of surgery in patients with severe/refractory CD requiring a disease re-evaluation. This tool could be of value in clinical practice, serving as the basis for a tailored management of CD patients.

Su1205 Long-Term Outcome of Treatment With Infliximab in Patients With Steroid-Dependent Ulcerative Colitis

Results: All patients demonstrated a pronounced reduction in their colitis activity index within 1 week following a single intracolonic dose of DIMS0150. Further improvements were evident at week 4 resulting in a clinical response and remission rate for the single dose treatment of 71% (8/11) and 27% (3/11) respectively. By week 12, the clinical response and remission rates had reached 91% (10/11) and 73% (8/11) respectively. Endoscopic remission rates in the single dose group were 27% (3/11) at week 4 and 45% (5/11) at week 12. Marked histological improvement was observed in 64% (7/11) of the single dose treated patients at week 12. Those patients who received three doses of DIMS0150 demonstrated an improved response to the measured parameters when compared to those patients who received a single dose of DIMS0150. A follow-up period of over 3 years post treatment indicated that 85% (12/14) of the treated patients had avoided the need for colectomy giving a colectomy rate of <10% per year with the longest patient being in symptom free remission for over 40 months. Conclusions: DIMS0150 has the potential to be an effective agent for treatment refractory chronic active ulcerative colitis patients with the prospect to avoid colectomy on a long term basis and is currently the subject of a clinical phase III study (EudraCT number: 2011 003130 14).

Diagnostic Accuracy of Ultrasonography in the Detection of Postsurgical Recurrence in Crohn’s Disease: A Systematic Review with Meta-analysis

Background and aims The postoperative course of Crohns disease (CD) is best predicted by ileocolonoscopy. Ultrasonography (US) has been proposed as indicator for postsurgical recurrence (PSR), but further confirmation is needed. We performed a systemic review with meta-analysis to assess the pooled diagnostic accuracy of US in the evaluation of PSR. Methods The systematic review was performed in PubMed/MEDLINE, EMBASE, SCOPUS, and Cochrane databases to identify studies assessing the US accuracy in PSR diagnosis. A sub-analysis between bowel sonography (BS), small-intestine contrast ultrasound (SICUS), and contrast-enhanced ultrasound (CEUS) was performed. Pooling was performed using diagnostic fixed or random-effect model according with heterogeneity. Results Ten studies (536 patients) met the inclusion criteria. There was no publication bias. Pooled sensitivity and specificity of US in detecting PSR were 0.94 (95% CI, 0.86-0.97) and 0.84 (95% CI, 0.62-0.94; diagnostic accuracy 90%), respectively. At sub-analysis, pooled sensitivity and specificity were 0.82 (95% CI, 0.76-0.88) and 0.88 (95% CI, 0.74-0.95) respectively for BS, with 0.99 (95% CI, 0.99-1.00) and 0.74 (95% CI, 0.73-0.74) for SICUS. Finally, an SROC curve was built to establish the best bowel wall thickness (BWT) cutoff able to predict the presence of severe PSR (Rutgeerts ≥3): a BWT ≥5.5 mm at US revealed sensitivity of 83.8% (95% CI, 73.6%-90.6%), specificity of 97.7% (95% CI, 93%-99%). Conclusions US shows high sensitivity and specificity for the diagnosis of PSR. SICUS appears more sensitive-but less specific-than BS, while the role of CEUS needs further investigation. A cutoff value of BWT ≥5.5 mm is strongly indicative of severe PSR. 10.1093/ibd/izy012_video1izy012.video15775249754001.

Beyond Irritable Bowel Syndrome: The Efficacy of the Low Fodmap Diet for Improving Symptoms in Inflammatory Bowel Diseases and Celiac Disease

Background and Aim: To evaluate the usefulness of a low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) diet on patients with irritable bowel syndrome (IBS), non-active inflammatory bowel diseases (IBD), and celiac disease (CD) on a gluten-free diet (GFD). Methods: Dietetic interventional prospective study. IBS, IBD, and CD subjects were evaluated to check if they fulfilled the Rome III criteria. Each subject was educated to follow a low FODMAP diet after being evaluated by filling out questionnaires that assessed the quality of life (QoL) and symptoms experienced (IBS-SSS and SF-36), and was reevaluated after 1 and 3 months. Results: One hundred twenty-seven subjects were enrolled: 56 with IBS, 30 with IBD, and 41 with CD. IBS-SSS showed that abdominal symptoms improved after 1 and 3 months of diet in all subjects, with significant difference among the 3 groups at T0 (average scores IBS: 293 ± 137, IBD: 206 ± 86, CD: 222 ± 65, p < 0.001), but no difference at T3 (IBS: 88 ± 54, IBD: 73 ± 45, CD: 77 ± 49, p = ns). By analyzing the SF-36 questionnaire, we did not observe any difference between the 3 groups, in terms of response to diet (p = ns), we observed a clinical improvement from T0 to T3 for most of the questionnaire’s domains. Conclusions: A low FODMAP diet could be a valid option to counter abdominal symptoms in patients with IBS, non-active IBD, or CD on a GFD, and thus, improve their QoL and social relations.