Ahmed Madisch

Oral Budesonide for Maintenance Treatment of Collagenous Colitis: A Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND & AIMS Oral budesonide effectively induces clinical remission in patients with collagenous colitis, a debilitating illness characterized by chronic watery/loose diarrhea, but there is a high rate of relapse after treatment cessation. METHODS This randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of long-term therapy with oral budesonide (Entocort CIR capsules) for maintenance of clinical remission of collagenous colitis. Patients were aged >18 years with histologically proven collagenous colitis and >3 watery/loose stools per day on >or=4 of the prior 7 days. Open-label oral budesonide 9 mg/d was administered to all patients for 6 weeks. Patients in clinical remission (<or=3 stools per day) at week 6 were subsequently randomized to double-blind oral treatment with budesonide 6 mg/d or matching placebo for 6 months. Relapse was defined as >3 stools per day on >or=4 consecutive days (and included patients withdrawn because of adverse events). RESULTS Of 48 enrolled patients, 46 (96%) achieved clinical remission at week 6 and were randomized to maintenance budesonide or placebo. There were 21 relapses during maintenance therapy, and almost all occurred during the first 2 months. Budesonide therapy was associated with a significantly lower cumulative rate of relapse compared with placebo (6/23 [26%] and 15/23 [65%], respectively; P = .022), and high correlation between clinical remission and histologic improvement was observed. Budesonide was well tolerated with no serious adverse events. CONCLUSIONS Oral budesonide 6 mg/d is efficacious and well tolerated for long-term maintenance of clinical remission in patients with collagenous colitis.

Budesonide Is Effective in Treating Lymphocytic Colitis: A Randomized Double-Blind Placebo-Controlled Study

BACKGROUND & AIMS Budesonide is effective in treating collagenous colitis, but no treatment is established for lymphocytic colitis. We performed a randomized, double-blind, placebo-controlled study to evaluate the effects of budesonide in patients with lymphocytic colitis. METHODS Forty-two patients (median age, 61 years) with lymphocytic colitis and chronic diarrhea were randomly assigned to groups that were given oral doses of budesonide (9 mg/d) or placebo for 6 weeks. Nonresponders at week 6 were given open-label budesonide (9 mg/d) for 6 additional weeks. A complete colonoscopy and histologic and quality-of-life analyses were performed at baseline and at week 6. The primary end point was clinical remission at 6 weeks, with last observation carried forward (LOCF). All patients who left the study in clinical remission were followed for relapse. RESULTS At week 6, 86% of patients given budesonide were in clinical remission (with LOCF) compared with 48% of patients given placebo (P = .010). Furthermore, open-label budesonide therapy induced clinical remission in 7 of 8 patients given placebo. Histologic remission was observed in 73% of patients given budesonide compared with 31% given placebo (P = .030). Only 1 patient discontinued budesonide therapy prematurely. During a mean follow-up period of 14 months, 15 patients (44.1%) experienced a clinical relapse (after a mean of 2 months); 8 of the relapsing patients were retreated with and responded again to budesonide. CONCLUSIONS Budesonide effectively induces clinical remission in patients with lymphocytic colitis and significantly improves histology results after 6 weeks. Clinical relapses occur but can be treated again with budesonide.

A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis

Objective To investigate the efficacy and safety of two different budesonide formulations (effervescent tablet for orodispersible use (BET) and viscous suspension (BVS)) with different daily dosages for short-term treatment of eosinophilic oesophagitis (EoE). Design Adults with active EoE (n=76) randomly received 14 days’ treatment with either BET 2×1 mg/day (BET1, n=19) or BET 2×2 mg/day (BET2, n=19), or BVS 2×5 mL (0.4 mg/mL)/day (BVS, n=19) or placebo (n=19) in a double-blind, double-dummy fashion, with a 2-week follow-up. Primary end point was histological remission (mean of <16 eosinophils/mm2 hpf). Secondary end points included endoscopy score, dysphagia score, drug safety and patients preference for drug formulation. Results Histological remission occurred in 100%, 94.7% and 94.7% of budesonide (BET1, BET2, BVS, respectively) and in 0% of placebo recipients (p<0.0001). The improvement in total endoscopic intensity score was significantly higher in the three budesonide groups compared with placebo. Dysphagia improved in all groups at the end of treatment; however, improvement of dysphagia persisted only in those treated with BET1 (p=0.0196 vs placebo). There were no serious adverse events. Local fungal infection (stained fungi) occurred in two patients of each budesonide group (10.5%). The effervescent tablet was preferred by 80% of patients. Conclusions BET or BVS was highly effective and safe for short-term treatment of EoE. The 1 mg (twice daily) dosage was equally effective as the 2 mg twice daily dosage. The majority of patients preferred the effervescent tablet formulation. ClinicalTrials.gov number NCT02280616; EudraCT number, 2009-016692-29.

One‐Week Once‐Daily Triple Therapy with Esomeprazole, Moxifloxacin, and Rifabutin for Eradication of Persistent Helicobacter pylori Resistant to Both Metronidazole and Clarithromycin

Aim:  To investigate a 1‐week once‐daily triple therapy with esomeprazole, moxifloxacin, and rifabutin for rescue therapy of Helicobacter pylori infection.

Psychometric validation of the German translation of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire in patients with reflux disease

BackgroundSymptoms of heartburn has an impact on health-related quality of life (HRQL). When a questionnaire is translated into a new language, a linguistic validation is necessary but not sufficient unless the psychometric characteristics have been verified. The aim is to document the psychometric characteristics of the German translation of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire.Methods142 patients with symptoms of heartburn (Age: M = 47.5, ± 14.6; Males = 44.4%) completed the German translation of GSRS, the QOLRAD, the Short-Form-36 (SF-36) and the Hospital Anxiety and Depression (HAD) scale.ResultsThe internal consistency reliability of GSRS ranged from 0.53–0.91 and of QOLRAD from 0.90–0.94, respectively. The test-retest reliability of GSRS ranged from 0.49–0.73 and of QOLRAD from 0.70–0.84. The relevant domains of the GSRS and QOLRAD domain scores significantly correlated. GSRS domains of Abdominal Pain and Constipation correlated (negatively) with most of the domains of the SF-36. The relevant QOLRAD domains significantly correlated with all SF-36 domains.ConclusionsThe psychometric characteristics of the German translation of GSRS and QOLRAD were found to be good, with satisfactory reliability and validity. The reliability of the GSRS Abdominal Pain domain was moderate.

Budesonide Is More Effective Than Mesalamine or Placebo in Short-term Treatment of Collagenous Colitis

BACKGROUND & AIMS Studies reporting that budesonide is effective for the treatment of collagenous colitis have been small and differed in efficacy measures. Mesalamine has been proposed as a treatment option for collagenous colitis, although its efficacy has never been investigated in placebo-controlled trials. We performed a phase 3, placebo-controlled, multicenter study to evaluate budesonide and mesalamine as short-term treatments for collagenous colitis. METHODS Patients with active collagenous colitis were randomly assigned to groups given pH-modified release oral budesonide capsules (9 mg budesonide once daily, Budenofalk, n = 30), mesalamine granules (3 g mesalamine once daily, Salofalk, n = 25), or placebo for 8 weeks (n = 37) in a double-blind, double-dummy fashion. The study was conducted in 31 centers (hospital clinics and private practices) in Germany, Denmark, Lithuania, Spain, and the United Kingdom. The primary end point was clinical remission at 8 weeks defined as ≤ 3 stools per day. Secondary end points included clinical remission at 8 weeks, according to the Hjortswang-Criteria of disease activity, taking stool consistency into account. RESULTS A greater percentage of patients in the budesonide group were in clinical remission at week 8 than the placebo group (intention-to-treat analysis, 80.0% vs 59.5%; P = .072; per-protocol analysis, 84.8% vs 60.6%; P = .046). Based on the Hjortswang-Criteria, 80.0% of patients given budesonide achieved clinical remission compared with 37.8% of patients given placebo (P = .0006); 44.0% of patients given mesalamine achieved clinical remission, but budesonide was superior to mesalamine (P = .0035). Budesonide significantly improved stool consistency and mucosal histology, and alleviated abdominal pain. The rate of adverse events did not differ among groups. CONCLUSIONS Oral budesonide (9 mg once daily) is effective and safe for short-term treatment of collagenous colitis. Short-term treatment with oral mesalamine (3 g once daily) appears to be ineffective. ClinicalTrials.gov number, NCT00450086.

Randomized trial on 14 versus 7 days of esomeprazole, moxifloxacin, and amoxicillin for second-line or rescue treatment of Helicobacter pylori infection.

Background:  Triple therapy with a proton pump inhibitor, moxifloxacin, and amoxicillin has been proven effective in first‐line treatment of Helicobacter pylori infection.

Allelic Variation of the Matrix Metalloproteinase-9 Gene Is Associated with Collagenous Colitis

Background: Collagenous colitis is a chronic inflammatory bowel disease of unknown origin characterized by a thickened subepithelial collagen layer. Differential expression of matrix‐metalloproteinases (MMPs) have been implicated in the pathogenesis of collagenous colitis. The aim was to assess genetic polymorphisms of MMP‐1, ‐7, and ‐9 in a case‐control setting for susceptibility to collagenous colitis. Methods: Seventy‐five patients with symptomatic collagenous colitis and 334 healthy blood donors were genotyped for single nucleotide polymorphisms (SNPs) in MMP‐1‐1607, MMP‐7‐153, MMP‐7‐181, and MMP‐9 exon 6 using TaqMan technology. Susceptibility to collagenous colitis was tested by comparison of the carrier status of the rare allele. Results: The carrier frequency of the allele GG of the coding SNP MMP‐9 in exon 6 was 24% in patients with collagenous colitis and 14.3% in healthy blood donors (P = 0.039). The carriage of the allele GG significantly increased the risk for collagenous colitis with an odds ratio of 1.9 (95% confidence interval: 1.0–3.5). None of the other SNPs of MMP‐1, MMP‐7‐153, and MMP‐7‐181 were associated with collagenous colitis. Conclusions: Allelic variation in the MMP‐9 gene may be part of a complex genetic risk profile for collagenous colitis. Further studies are needed to confirm this observation and to explore the functional role of this gene polymorphism in collagenous colitis. (Inflamm Bowel Dis 2011;)

NOD2/CARD15 gene polymorphisms are not associated with collagenous colitis

BackgroundCollagenous colitis is a chronic inflammatory bowel disease of unknown origin. In some cases of collagenous colitis, histomorphological features are comparable to other inflammatory bowel diseases.AimTo assess functional NOD2/CARD15 polymorphisms for the susceptibility to collagenous colitis in a case-control study.Materials and methodsSeventy-five patients with symptomatic collagenous colitis and 534 healthy blood donors were genotyped for SNP 8, 12, and 13 of the NOD2/CARD15 gene using TaqMan technology. Susceptibility to collagenous colitis was tested using Chi2-test comparing the carrier status of the rare allele.ResultsThe carrier frequency of the rare allele in SNP 8, 12, and 13 was 9.5, 1.3, and 8.1% in patients with collagenous colitis and 8.9, 1.1, and 8.4% in healthy blood donors, respectively. There were no significant differences in allele-, genotype, and carrier frequency (p>0.05).ConclusionOur data suggest that functional polymorphisms in the NOD2/CARD15 gene might not be involved in the susceptibility to collagenous colitis.

Risk Factors for Symptom Relapse in Collagenous Colitis After Withdrawal of Short-term Budesonide Therapy

Background:Oral budesonide has been proven effective in short- and long-term treatment of collagenous colitis; however, symptom relapse frequently occurs after drug withdrawal. The aim of this study was to identify the risk factors for symptom relapse in patients with collagenous colitis after withdrawal of short-term budesonide therapy. Methods:One hundred twenty-three patients from 4 randomized controlled studies who achieved clinical remission after short-term treatment with budesonide (9 mg/d) were analyzed, including 40 patients receiving subsequent budesonide maintenance therapy (6 mg/d) for 6 months and 83 patients without active maintenance treatment. Variables available for analysis were age, sex, baseline stool frequency, duration of diarrhea, collagenous band thickness, and lamina propria inflammation. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated by Cox proportional hazard model. Results:The overall symptom relapse rate was 61%. By multivariate analysis, a baseline stool frequency >5 per day (HR, 3.95; 95% CI, 1.08–14.39), history of diarrhea >12 months (HR, 1.77; 95% CI, 1.04–3.03), and the absence of budesonide maintenance therapy (HR, 2.71; 95% CI, 1.37–5.38) were associated with symptom relapse. The time to relapse was shorter in patients with a baseline stool frequency >5 per day (56 versus 199 d, P = 0.024), as in those with history of diarrhea >12 months (56 versus 220 d, P = 0.009). Budesonide maintenance therapy delayed the time to relapse (56 versus 207 d, P = 0.005). Conclusions:Our data demonstrate that a high stool frequency at baseline and a long duration of diarrhea are risk factors for symptom relapse in collagenous colitis, whereas budesonide maintenance therapy is a protective factor against symptom relapse.