Clinical trial: Preliminary efficacy and safety study of a new Budesonide-MMX® 9 mg extended-release tablets in patients with active left-sided ulcerative colitis

BackgroundUlcerative colitis (UC) is a chronic inflammatory disease with relapses. Many patients need systemic corticosteroids to induce clinical remission.AimEfficacy and safety of Budesonide-MMX^® 9 mg tablets, a new oral, extended-release formulation, were evaluated in patients suffering from active, left-sided UC with colitis activity index (CAI) < 14.Methods36 patients were treated once daily for 4 weeks with Budesonide-MMX^® 9 mg tablets or placebo. In an additional 4-week period, all patients received Budesonide-MMX^®. CAI, endoscopic index and histology were assessed after 4 and 8 weeks. Primary end-point was remission, and/or CAI reduction by 50% after 4 weeks. Morning cortisol was assayed after 4 and 8 weeks, and a short ACTH-test was performed at week 8.Results32 patients were analysed. After 4 weeks, 47.1% of the patients in the Budesonide-MMX^® 9 mg tablets group achieved the primary end-point vs. 33.3% of patients on placebo. In addition, 47.1% of budesonide patients and another 33.3% of placebo recipients improved without remission by 4 weeks. The CAI reduction was significant with Budesonide (p < 0.0001) tablets and not with placebo (p = 0.1). Neither morning cortisol nor pituitary–adrenal axis was more frequently suppressed with Budesonide tablets than with placebo.ConclusionsBudesonide-MMX^® 9 mg tablets induced a fast and significant clinical improvement of active left-sided UC without suppression of adrenocortical functions and without important toxicity EudraCT number 2004-000896-33.     

Induction with NCB-02 (curcumin) enema for mild-to-moderate distal ulcerative colitis — A randomized,placebo-controlled,pilot study

Background and aimsCurcumin, an active ingredient of turmeric with anti-inflammatory properties, has been demonstrated to be useful in experimental models of ulcerative colitis (UC). It's efficacy in humans needs to be investigated.MethodsA randomized, double-blind, single-centre pilot trial was conducted in patients with distal UC (< 25 cm involvement) and mild-to-moderate disease activity. Forty-five patients were randomized to either NCB-02 (standardized curcumin preparation) enema plus oral 5-ASA or placebo enema plus oral 5-ASA. Primary end point was disease response, defined as reduction in Ulcerative Colitis Diseases Activity Index by 3 points at 8 weeks, and secondary end points were improvement in endoscopic activity and disease remission at 8 weeks.ResultsResponse to treatment was observed in 56.5% in NCB-02 group compared to 36.4% (p = 0.175) in placebo group. At week 8, clinical remission was observed in 43.4% of patients in NCB-02 group compared to 22.7% in placebo group (p = 0.14) and improvement on endoscopy in 52.2% of patients in NCB-02 group compared to 36.4% of patients in placebo group (p = 0.29). Per protocol analysis revealed significantly better outcomes in NCB-02 group, in terms of clinical response (92.9% vs. 50%, p = 0.01), clinical remission (71.4% vs. 31.3%, p = 0.03), and improvement on endoscopy (85.7% vs. 50%, p = 0.04).ConclusionIn this pilot study we found some evidence that use of NCB-02 enema may tend to result in greater improvements in disease activity compared to placebo in patients with mild-to-moderate distal UC. The role of NCB-02 as a novel therapy for UC should be investigated further.     

Evaluation of unmet medical need among Japanese patients with type 2 diabetes mellitus and efficacy of Lixisenatide treatment among Asian type 2 diabetes mellitus patients

AimsThis study determined the unmet medical need of basal insulin therapy among type 2 diabetes patients who participated in the ALOHA study. Also a meta-analysis of the GetGoal-Duo1, -L, and -L-Asia trials was conducted to examine the impact of lixisenatide add-on treatment to basal insulin therapy ± OADs specifically among Asian type 2 diabetes patients.MethodsThe proportions of Japanese patients with an unmet need of diabetes management, defined as not achieving an HbA1c < 7% despite having a fasting plasma glucose (FPG) < 130 mg/dL, and without an unmet need, defined as having an endpoint HbA1c < 7%, regardless of FPG level, were determined for the ALOHA study population, which was conducted as a post-marketing survey for insulin glargine in Japan. For the meta-analysis, all Asian modified intent-to-treat patients with baseline and endpoint HbA1c measurements reported from the 3 GetGoal trials were included.ResultsAmong 1013 Japanese type 2 diabetes patients in the ALOHA study, 36% had an unmet need. In the GetGoal-Duo1, -L, and L-Asia trials, 237 Asian patients were treated with lixisenatide add-on treatment to basal insulin and 226 received placebo. Lixisenatide add-on treatment vs. placebo was associated with the following significant mean changes in efficacy outcomes at week 24: HbA1c: −0.6%, p = 0.005; FPG: −13.3 mg/dL, p = 0.004; PPG: −101.4 mg/dL, p < 0.001; weight: −0.5 kg, p = 0.018; basal insulin dose: −1.6 U, p < 0.001.ConclusionsLixisenatide add-on treatment may provide a viable option to address the unmet need of basal insulin therapy among Asian type 2 diabetes patients.     

Role of faecal calprotectin as a predictor of endoscopic activity in paediatric patients with ulcerative colitis

IntroductionColonoscopy is currently considered to be the gold standard for evaluation of colonic mucosa inflammation in patients with ulcerative colitis (UC), but the procedure is invasive and cannot be repeated frequently, especially in the paediatric population. The aim of this study was to assess the role of faecal calprotectin (FC) as a predictor of endoscopic disease activity in paediatric patients with UC in clinical remission.Material and methodsSingle-centre prospective study. Clinical remission was defined as Paediatric Ulcerative Colitis Activity Index <10. Endoscopic findings were assessed according to the Mayo Endoscopic Subscore (MES). MES ≤ 1 was defined as endoscopic remission. All participants provided fresh faecal samples for measurement of FC.ResultsA total of 34 visits of 24 children with UC were included in the study. There was a strong positive correlation between FC levels and endoscopic disease activity (n = 34, r = 0.83, p < 0.001). The median FC levels in the subgroup with endoscopic activity (MES 2–3) were significantly higher than the median FC levels in the subgroup without endoscopic activity (MES ≤ 1) (1000 μg/g, IQR 575–1800 μg/g vs. 100 μg/g, IQR 80–223 μg/g, p < 0.001). At a cut-off of 298.5 μg/g, FC had 92.3% sensitivity, 95.2% specificity and an AUROC 0.974 (SE 0.023, 95% CI 0.93–1, p < 0.001) to predict endoscopic activity.DiscussionFC is an accurate surrogate marker of endoscopic activity in children with clinically quiescent UC.     

The Patient Simple Clinical Colitis Activity Index (P-SCCAI) can detect ulcerative colitis (UC) disease activity in remission: A comparison of the P-SCCAI with clinician-based SCCAI and biological markers

AimTo develop a patient-based Simple Clinical Colitis Activity Index (P-SCCAI) of ulcerative colitis (UC) activity and to compare it with the clinician-based SCCAI, C-reactive protein (CRP) and Physician's Global Assessment (PGA) of UC activity. Monitoring UC activity may give patients disease control and prevent unnecessary examinations.MethodsConsecutive UC patients randomly completed the P-SCCAI either before or after consultation. Gastroenterologists assessed patients' UC activity on the same day. Overall agreement between SCCAI and P-SCCAI was calculated with Spearman's Rho and Mann–Whitney U test. Agreement regarding active disease versus remission and agreement at domain level were calculated by percent agreement and kappa (κ).Results149 (response rate 84.7%) UC patients participated. P-SCCAI and SCCAI showed a large correlation (r_s = 0.79). The medians (IQR) of the P-SCCAI (3.78;0–15) tended to be higher than those of the SCCAI (2.86;0–13), although this difference did not reach statistical significance (z = 1.71| p = 0.088). In 77% of the cases the difference between clinicians' and patients' scores was not clinically different (i.e. ≤ 2). Percentage agreement between clinicians and patients, judging UC as active or in remission, was 87%, r_s = 0.66, κ = 0.66, indicating a substantial agreement. In general patients tended to report more physical symptoms than clinicians. C-Reactive protein (CRP) was found to have a significant association with both P-SCCAI and SCCAI (κ = 0.32, κ = 0.39 respectively) as was PGA (κ = 0.73 for both indices).ConclusionsThe P-SCCAI is a promising tool given its substantial agreement with the SCCAI and its feasibility. Therefore, P-SCCAI can complement SCCAI in clinical care and research.     

Mucosal healing with oral tacrolimus is associated with favorable medium- and long-term prognosis in steroid-refractory/dependent ulcerative colitis patients

BackgroundOral administration of tacrolimus is an effective remission induction therapy for steroid-refractory/dependent ulcerative colitis (UC).AimThis study aimed to evaluate the short- as well as medium- and long-term effectiveness of tacrolimus therapy.MethodsThe medical records of 51 patients treated with tacrolimus for UC at our hospital between July 2009 and December 2011 were reviewed retrospectively. Clinical remission and improvement were defined as a Lichtiger score of 4 or less and as a Lichtiger score of ≤ 10 and a reduction in the score of ≥ 3 compared with the baseline score, respectively. Endoscopic findings were evaluated based on the endoscopic activity index and Mayo endoscopic score.ResultsThe clinical effectiveness combining clinical remission and improvement was observed in 62.7% of the patients at 3 months. Thirty-six patients underwent colonoscopy at 3 months, and 12 (33.3%) and 10 patients (27.8%) showed Mayo endoscopic scores of 0 and 1, respectively. On Kaplan–Meier analysis, the overall percentage of event-free survivors, who did not require colectomy nor switching to other induction therapy such as infliximab, was 73.0% at 6 months, 49.9% at 1 year, and 37.8% at 2 years. Patients with a Mayo endoscopic score of 0–1 at 3 months showed significantly better medium- and long-term prognosis than those with a score of 2–3 (p < 0.01). All adverse events, including infections in 2 patients, were reversible.ConclusionsTacrolimus therapy was effective for inducing clinical and endoscopic remission of steroid-refractory/dependent UC. Endoscopic improvement was associated with favorable medium- and long-term prognosis.     

Does fecal calprotectin predict relapse in patients with Crohn's disease and ulcerative colitis?

Background and aimsAn evaluation is made of the utility of fecal calprotectin in predicting relapse in patients with inflammatory bowel disease (IBD). The possible differences in its predictive capacity in Crohn's disease (CD) versus ulcerative colitis (UC), and the different phenotypes, are also examined.MethodsThis is a prospective study with 135 patients diagnosed with IBD in clinical remission for at least 3 months. The patients submitted a stool sample within 24 hours after the baseline visit, for the measurement of fecal calprotectin. All patients were followed-up on for one year.ResultsSixty-six patients had CD and 69 UC. Thirty-nine (30%) suffered from relapse. The fecal calprotectin concentration was higher among the patients with relapse than in those that remained in remission: 444 µg/g (95% CI 34–983) versus 112 µg/g (95% CI 22–996); p < 0.01. Patients with CD and calprotectin > 200 µg/g relapsed 4 times more often than those with lower marker concentrations. In UC, calprotectin > 120 µg/g was associated with a 6-fold increase in the probability of disease activity outbreak. The predictive value was similar in UC and CD with colon involvement and inflammatory pattern. In this group, calprotectin > 120 µg/g predicted relapse risk with a sensitivity of 80% and a specificity of 60%. Relapse predictive capacity was lower in patients with ileal disease.ConclusionsFecal calprotectin may be a useful marker for predicting relapse in patients with IBD. Its predictive value is greater in UC and CD with colon involvement and inflammatory pattern, compared with ileal CD.     

Role and mechanisms of action of Escherichia coli Nissle 1917 in the maintenance of remission in ulcerative colitis patients: An update

Ulcerative colitis (UC) is a chronic inflammatory disease, whose etiology is still unclear. Its pathogenesis involves an interaction between genetic factors, immune response and the “forgotten organ”, Gut Microbiota. Several studies have been conducted to assess the role of antibiotics and probiotics as additional or alternative therapies for Ulcerative Colitis. Escherichia coli Nissle (EcN) is a nonpathogenic Gram-negative strain isolated in 1917 by Alfred Nissle and it is the active component of microbial drug Mutaflor^® (Ardeypharm GmbH, Herdecke, Germany and EcN, Cadigroup, In Italy) used in many gastrointestinal disorder including diarrhea, uncomplicated diverticular disease and UC. It is the only probiotic recommended in ECCO guidelines as effective alternative to mesalazine in maintenance of remission in UC patients. In this review we propose an update on the role of EcN 1917 in maintenance of remission in UC patients, including data about efficacy and safety. Further studies may be helpful for this subject to further the full use of potential of EcN.     

Saxagliptin efficacy and safety in patients with type 2 diabetes receiving concomitant statin therapy

AimsTo examine whether concomitant statin therapy affects glycemic control with saxagliptin 2.5 and 5 mg/d in patients with type 2 diabetes mellitus (T2DM).MethodsEfficacy and safety were analyzed post hoc for pooled data from 9 saxagliptin randomized, placebo-controlled trials with a primary 24-week treatment period (4 monotherapy, 2 add-on to metformin, 1 each add-on to a sulfonylurea, thiazolidinedione, or insulin ± metformin). Safety was also assessed in an 11-study, 24-week pool and an extended 20-study pool, which included 9 additional 4- to 52-week randomized studies. Comparisons were performed for patient groups defined by baseline statin use.ResultsSaxagliptin produced greater mean reductions in glycated hemoglobin than placebo, with no interaction between treatment and baseline statin use (P = 0.47). In patients receiving saxagliptin 2.5 and 5 mg and placebo, the proportion of patients with ≥ 1 adverse event (AE) was 78.1%, 64.0%, and 63.2%, respectively, in patients with any statin use and 70.6%, 57.9%, and 55.0% in patients with no statin use. Serious AEs, deaths, and symptomatic confirmed hypoglycemia (fingerstick glucose ≤ 50 mg/dL) were few and similar, irrespective of baseline statin use.ConclusionsSaxagliptin improves glycemic control and is generally well tolerated in patients with T2DM, irrespective of concomitant statin therapy.     

Sustained remission after steroids and leukocytapheresis induced response in steroid-dependent ulcerative colitis: Results at 1 year

BackgroundLeukocytapheresis (LAP) could be an alternative treatment for steroid-dependent ulcerative colitis (UC).AimsTo assess the duration of response at 1 year after this treatment.Patients and methodsA prospective study in 18 patients with steroid-dependent UC treated with LAP plus steroids after failure or intolerance to immunomodulators. Clinical and endoscopic (Mayo Clinic index) examinations were performed at 1 month after the last apheresis and at 12 months. The clinical, endoscopic remission and the relapse during the 1-year follow-up were evaluated based on standard parameters.ResultsInduction of remission: clinical remission: 10/18 (55%). Partial response: 4. Endoscopic remission: 9 (50%), always accompanied by clinical remission. A significant correlation was observed between clinical remission and endoscopic remission (r_s = 0.894; p ≤ 0.001). At 1 year: sustained steroid-free clinical remission in 9 (50%), all of whom presented initial endoscopic remission. Remission and relapse before 1 year in 17%. A tendency for sustained remission at 1 year was observed when initial endoscopic remission was achieved.ConclusionsInitial remission can be maintained at 1 year in half of the patients without the need for additional steroids. Complete remission and endoscopic mucosal healing is proposed as an objective for achieving a lasting response.     

Granulocytapheresis in steroid-dependent and steroid-resistant patients with inflammatory bowel disease: A prospective observational study

BackgroundDespite the mounting importance of granulocytapheresis (GCAP) for inflammatory bowel disease (IBD) treatment, its effectiveness in steroid-dependent (SD) and steroid-resistant (SR) patients has not been clearly evaluated. This prospective observational study describes the use of GCAP in SD and SR patients with either Ulcerative Colitis (UC) or Crohn's Disease (CD).Methods118 patients, 83 affected by UC (55 SD and 28 SR) and 35 by CD (22 SD and 13 SR), were treated with GCAP, using Adacolumn™, for 5 consecutive weeks, 1 session/week. All patients were followed for 12 months after the end of GCAP. Clinical remission was defined as Clinical Activity Index (CAI) ≤ 6 for UC patients and Crohn's Disease Activity Index (CDAI) < 150 for CD patients.ResultsAll patients completed the study; no major complications were reported. At the end of GCAP 71% of UC and 63% of CD patients showed clinical remission. At 6 months the remission was maintained by 66% and 54% of UC and CD patients respectively, while at 12 months the percentages were 48% and 43%, respectively. No differences between SD and SR subgroups were reported at any timepoint. CAI and CDAI values significantly dropped after GCAP treatment and at 6 and 12 months' follow-up (p < 0.05 vs baseline for both timepoints). No differences were measured in CAI and CDAI between SD and SR patients.ConclusionGCAP therapy is safe and effective in inducing and maintaining clinical remission both in SD and in SR patients affected by either UC or CD.     

Clinical status,psychosocial impairments,medical treatment and health care costs for patients with inflammatory bowel disease (IBD) in Germany: An online IBD registry

BackgroundThe aim of this cross-sectional study was to establish an online inflammatory bowel disease (IBD) registry for a first picture of the situation of IBD outpatients' treatment in Germany.MethodsBetween March 2006 and July 2007 IBD outpatients from 24 gastroenterological specialist practices and two hospitals in Germany were enrolled in an Internet-based registry to evaluate the outpatients' clinical status, psychological impairments, provided health care, as well as medical treatment and medication costs.Results1032 IBD patients (ulcerative colitis/UC: 519; Crohn's disease/CD: 511; indeterminate colitis: 2) were enrolled in the study (age: 43 ± 14 years/M ± SD). Disease duration of all patients averaged 10 ± 8.5 years. In 519 UC-patients (49% male; 33% pancolitis), 66% were in remission as were 55% of CD patients (37 % male; 41 % active smokers). Associated with higher rates of disease activity (CDAI ≥ 150; CAI > 4) were corticosteroids (CD, UC), topical medication (UC), relevant reported depressive symptoms (15%; 6-31%) and impairments in sexuality (21%; 9-42%). Relevant medication groups prescribed were oral aminosalicylates (UC: 70%; CD: 47%); immunosuppressive therapy - mostly azathioprine/6 MP (CD: 47%; UC: 26%), and Infliximab (CD: 8%; UC: 3%).Strongly associated with their clinical disease activity in UC as well as CD patients, 15% (6–31%) reported relevant depressive symptoms and 21% (9–42%) relevant impairments in sexuality.ConclusionsThe registry constitutes a large complemental database for the patient population in Germany. About one third of the IBD patients were not in clinical remission (CDAI ≥ 150/CAI > 4) (CD: 45%; UC: 27%), although high rates of immunosuppressive drugs (CD: 47%; UC 26%) were administered. This study shows a large burden of active disease associated with an unexpectedly high (co)morbidity and high psychosocial impairments, indicating a reduced health state in IBD patients.     

Subgroup analysis of the placebo-controlled CHARM trial: Increased remission rates through 3 years for adalimumab-treated patients with early Crohn's disease

Background and aimsWe examined the impact of disease duration on clinical outcomes and safety in a post hoc analysis of a remission maintenance trial with adalimumab in patients with moderate to severe CD.MethodsPatients in the CHARM trial were divided into 3 disease duration categories: < 2 (n = 93), 2 to < 5 (n = 148), and ≥ 5 years (n = 536). Clinical remission and response rates at weeks 26 and 56 were compared between adalimumab and placebo subgroups, and assessed through 3 years of adalimumab treatment in the ADHERE follow-on trial. Logistic regression assessed the effect of disease duration and other factors on remission and safety.ResultsAt week 56, clinical remission rates were significantly greater for adalimumab-treated versus placebo-treated patients in all 3 duration subgroups (19% versus 43% for < 2 years; P = 0.024; 13% versus 30% for 2 to < 5 years; P = 0.028; 8% versus 28% for ≥ 5 years, P < 0.001). Logistic regression identified shorter duration as a significant predictor for higher remission rate in adalimumab-treated patients. Patients with disease duration < 2 years maintained higher remission rates than patients with longer disease duration through 3 years of treatment. The incidence of serious adverse events in adalimumab-treated patients was lowest with disease duration < 2 years.ConclusionsAdalimumab was superior to placebo for maintaining clinical remission in patients with moderately to severely active CD after 1 year of treatment regardless of disease duration. Clinical remission rates through 3 years of treatment were highest in the shortest disease duration subgroup in adalimumab-treated patients, with a trend to fewer side effects.     

Serum adenosine deaminase activity as a predictor of disease severity in ulcerative colitis

Background and aimUlcerative colitis (UC) is a chronic inflammatory disease characterized by recurrent inflammation and ulcerations of colonic mucosa and an inappropriate and delayed healing. Adenosine deaminase (ADA) is a cytoplasmic enzyme involved in the catabolism of purine bases, capable of catalyzing the deamination of adenosine, forming inosine in the result process. Although ADA has been shown to increase in several inflammatory conditions, there are no literature data indicating an alteration in UC.MethodsThis study evaluated the activity of total ADA in serum of 43 patients with UC and 18 healthy controls. Patients’ age, disease duration, drug intake, and other medical history were all noted for each subject. Complete blood count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were determined for both patients and controls. Correlation analysis was also performed between ADA and other inflammation markers of UC.ResultsSerum mean ADA levels were 11.12 ± 2.03 and 7.99 ± 2.04 U/l for patients with UC in active state and in remission and 8.55 ± 2.26 U/l in the healthy control group. Mean serum ADA levels were significantly elevated in active UC patients compared with patients with UC in remission and control groups. Overall accuracy of ADA in determination of active UC was 83.7 with sensitivity 83.3%, specificity 84.2%.ConclusionsSerum ADA levels were found to be elevated in UC patients in active state suggesting a partial role of activated T-cell response in the disease pathophysiology. Further randomized controlled studies are warranted to demonstrate the role of ADA in UC patients, with a special interest in specifically targeted therapies against ADA for achieving disease remission.     

Oral tacrolimus as maintenance therapy for refractory ulcerative colitis—an analysis of outcomes in two London tertiary centres

BackgroundThe medical management of refractory ulcerative colitis (UC) remains a significant challenge. Two randomised controlled studies have demonstrated tacrolimus therapy is effective for the induction of remission of moderate to severe UC. However, the long term outcomes of UC patients treated with tacrolimus as maintenance therapy are not certain.AimsThis study aims to assess the efficacy of tacrolimus maintenance therapy for refractory UC.MethodsA retrospective review of patients with UC treated with tacrolimus at two London tertiary centres was performed. Clinical outcomes were assessed at six months, at the end of tacrolimus treatment, or at the last follow-up for patients continuing tacrolimus treatment. Modified Truelove–Witts score (mTW) and Mayo endoscopy subscores were calculated.Results25 patients with UC, treated with oral tacrolimus between 2005 and 2011, were identified. The median duration of tacrolimus treatment was 9 months (IQR 3.7–18.2 months). The median duration of follow-up was 27 months (range 3–66 months). At six months thirteen (52%) patients had achieved and maintained clinical response and eleven (44%) were in clinical remission. The mean mTW score decreased from 10 +/− 0.5 before therapy, to 5.8 +/− 0.8 (p ≤ 0.001 95% CI 2.7–5.8) at cessation of treatment or last follow-up. Mayo endoscopy subscore decreased from 2.6 +/− 0.1 to 1.2 +/− 0.2 (p ≤ 0.001 mean reduction 1.4, 95% CI 0.8–1.9). Eight patients (32%) subsequently underwent a colectomy within a mean time of 17 months (range 2–45 months).ConclusionTacrolimus is effective for the maintenance of refractory UC and can deliver sustained improvement in mucosal inflammation.     

Health-related quality of life and disability in patients with ulcerative colitis and proctocolectomy with ileoanal pouch versus treatment with anti-TNF agents

Background and aims:We compared health-related quality of life (HRQL) and disability in ulcerative colitis (UC) patients in remission with anti-tumor necrosis factor agents (TNF) or after restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA).MethodsTwo patient cohorts were studied. The first group consisted of patients in remission after RPC with IPAA (surgery group). The second group consisted of patients in remission with infliximab or adalimumab (medical group). For inclusion in the surgery group the pouch had to be functional for ≥ 1 year and patients were excluded in case of postoperative complications. In the medical group, patients had to be on maintenance therapy with anti-TNF agents for ≥ 1 year and in clinical remission. HRQL and disability outcomes were assessed using SF-36, COREFO, WPAI:UC and EORTC questionnaires.Results60 patients were included, 30 patients in both groups. 58 out of 60 patients (97%) returned the completed questionnaires: 29 patients in the surgery group (median age 42 years [22–67]; 48% female) and 29 patients in the medical group (median age 45 years [19–68]; 65% female). Patient characteristics were comparable between the two groups. There were no significant differences in SF-36, WPAI:UC and EORTC questionnaires between both groups, except for the medication and stool frequency scale (COREFO questionnaire) that was significantly higher in the surgery vs. the medical group (p = 0.004 and p < 0.001, respectively).ConclusionHRQL and disability were not different among the medical and surgical group, except for stool frequency and anti-diarrhea medication use that was significantly higher in surgically treated patients.     

Does Azathioprine induce endoscopic and histologic healing in pediatric inflammatory bowel disease? A prospective,observational study

BackgroundThe new concept of disease remission for pediatric inflammatory bowel diseases (IBD) implies the achievement of mucosal healing.AimsWe aimed to evaluate endoscopic and histologic healing in children with Ulcerative Colitis (UC) and Crohn’s disease (CD) in clinical remission after 52 weeks of Azathioprine.MethodsFrom December 2012 to July 2015 we prospectively enrolled IBD children starting Azathioprine. Enrolled patients in clinical remission underwent colonoscopy after 52 weeks. Macroscopic assessment was described with Mayo score and the simplified endoscopic score for UC and CD, respectively. For microscopic assessment, an average histology score was used. Data on inflammatory markers and fecal calprotectin were also collected.ResultsFourty-seven patients were included in the analysis. Endoscopic healing was detected in 20/26 (76.9%) UC children and 10/21 (47.6%) CD patients. Median Mayo score and simplified endoscopic score were significantly decreased at week 52 (p < 0.001; p = 0.005). Median average histology score was not significantly different at week 52 in both diseases. Fecal calprotectin was directly correlated with simplified endoscopic score (T0: r = 0.4, p = 0.05; T52: r = 0.5, p = 0.01), but not with Mayo score. No correlation was found between endoscopic and histologic scores.ConclusionsIBD children under Azathioprine reach endoscopic healing, but not histological remission.     

Bilberry ingestion improves disease activity in mild to moderate ulcerative colitis — An open pilot study

Background and aimsA significant fraction of patients with ulcerative colitis (UC) is not sufficiently controlled with conventional therapy or suffers from therapy related side effects. Anthocyanins, highly abundant in bilberries (Vaccinium myrtillus), were shown to have antioxidative and anti-inflammatory effects. We aimed to explore the therapeutic potential of bilberries in active UC.MethodsIn an open pilot trial with a total follow-up of 9 weeks the effect of a daily standardized anthocyanin-rich bilberry preparation was tested in 13 patients with mild to moderate UC. Clinical, biochemical, endoscopic and histologic parameters were assessed.ResultsAt the end of the 6 week treatment interval 63.4% of patients achieved remission, the primary endpoint, while 90.9% of patients showed a response. In all patients a decrease in total Mayo score was detected (mean: 6.5 and 3.6 at screening and week 7, respectively; p < 0.001). Fecal calprotectin levels significantly decreased during the treatment phase (baseline: mean 778 μg/g, range 192–1790 μg/g; end of treatment: mean 305 μg/g, range < 30–1586 μg/g; p = 0.049), including 4 patients achieving undetectable levels at end of treatment. A decrease in endoscopic Mayo score and histologic Riley index confirmed the beneficial effect. However, an increase of calprotectin levels and disease activity was observed after cessation of bilberry intake. No serious adverse events were observed.ConclusionsThis is the first report on the promising therapeutic potential of a standardized anthocyanin-rich bilberry preparation in UC in humans. These results clearly indicate a therapeutic potential of bilberries in UC. Further studies on mechanisms and randomized clinical trials are warranted.     

Fast and sharp decrease in calprotectin predicts remission by infliximab in anti-TNF naïve patients with ulcerative colitis

AimTo evaluate the effect of infliximab induction therapy on calprotectin levels in patients with ulcerative colitis (UC).Patients and MethodsIn this prospective study 53 patients with active UC from 17 centers were treated with infliximab therapy (5 mg/kg) at baseline, week 2, and week 6. Faecal calprotectin was measured every week. Sigmoidoscopies were performed at baseline, week 6 and week 10.ResultsMedian calprotectin levels decreased from 1260 (IQR 278.5- 3418 ) at baseline to 72.5 (IQR 18.5 - 463) at week 10 (p < 0.001). After 10 weeks, infliximab therapy induced endoscopic remission and a decrease in calprotectin to < 50 mg/kg or at least a 80% decrease from baseline level in 58% of patients.A significant and steep decrease of calprotectin levels was seen at week 2 for patients with an endoscopic remission at week 10 as compared to patients who did not show a remission. (p < 0.001).At week 10 an excellent correlation was found between endoscopic remission and clinical Mayo score reflected by an AUC of ROC analyses of 0.94 (0.87-1) and with calprotectin measurements (AUC 0.91 (0.81-1)) : all patients with calprotectin levels < 50 mg/kg, and a normal clinical Mayo score (= 0) were in endoscopic remission.ConclusionsInfliximab induces a fast and significant decrease of faecal calprotectin levels in anti-TNF naïve patients with ulcerative colitis predictive for remission of disease     

Clinical features and course of ulcerative colitis diagnosed in asymptomatic subjects

Background and AimsAlthough some ulcerative colitis (UC) patients are diagnosed when they do not have any UC-related symptoms, clinical features and prognosis of UC diagnosed in asymptomatic patients remain unclear.MethodsData for UC patients who were asymptomatic at diagnosis were retrospectively reviewed from the IBD database of the Asan Medical Center. The clinical characteristics and prognosis of those patients were analyzed and compared with matched (1:4) symptomatic UC patients.ResultsOnly nineteen asymptomatic UC patients (1.1%) were identified from 1665 UC patients. The proportion of males was 78.9% (n = 15), and their median age at diagnosis was 48 years (range, 34–71 years). At diagnosis, proctitis was noted in 11 patients (57.9%), left-sided colitis in 4 (21.1%), extensive colitis in 0 (0%), and atypical distribution in 4 (21.1%). The 5-year cumulative probability of symptom development was 68.5% (95% confidence interval [CI], 62.8%–74.2%). After UC diagnosis, oral 5-aminisalicylic acid (ASA) and topical 5-ASA were used in 14 (73.7%) and 16 (84.2%) patients, respectively. During follow-up (3.7-year median for asymptomatic patients versus 3.7-year median for symptomatic patients; P = 0.961), the 5-year cumulative probability of corticosteroids (23.7% versus 57.1%; P = 0.022) and azathioprine (0% versus 24.7%; P = 0.003) use was higher in symptomatic patients than in asymptomatic patients.ConclusionsThe frequency of asymptomatic UC patients was 1.1% in our UC patient cohort. A majority of these patients became symptomatic during follow-up. Asymptomatic UC patients at diagnosis appear to have a better prognosis than symptomatic UC patients.