Menthacarin, a Proprietary Peppermint Oil and Caraway Oil Combination, Improves Multiple Complaints in Patients with Functional Gastrointestinal Disorders: A Systematic Review and Meta-Analysis.

INTRODUCTION: This systematic review summarizes published data on Menthacarin, the proprietary combination of peppermint oil and caraway oil, in the treatment of functional gastrointestinal disorders. Efficacy was assessed by meta-analysis of placebo-controlled trials. METHODS: We searched PubMed, the Cochrane Library, and the manufacturer's information system for clinical studies investigating the safety and efficacy of Menthacarin. Efficacy analyses included change from baseline of epigastric pain and general improvement of the patients' condition. RESULTS: Five randomized trials involving 580 patients were found, demonstrating significant effects of Menthacarin on symptoms of functional dyspepsia (FD) compared to placebo or similar effects compared to a reference drug. Seven other studies reported favorable results on therapeutic application in FD patients with concomitant Helicobacter pylori infection, in irritable bowel syndrome (IBS), and on tolerability in FD patients from 12 years of age. Three trials in FD with 249 patients were eligible for meta-analysis. Results demonstrate a significant reduction in pain intensity (standardized mean difference: 0.80; 95% confidence interval (CI): 0.39-1.21) and in item 2 of the Clinical Global Impression Scale (risk ratio: 2.65; 95% CI: 1.81-3.87) for Menthacarin. CONCLUSIONS: Menthacarin was shown to be effective and safe for the treatment of FD and represents a promising option for symptoms of IBS.

[Treatment of eosinophilic esophagitis - advancements and perspectives]. / Therapie der eosinophilen Ösophagitis - Fortschritte und Perspektiven.

In recent years significant progress has been made in the treatment of eosinophilic esophagitis (EoE), especially in the area of topical corticosteroids. Novel EoE-specific formulations have been developed and first approvals have been obtained for induction and maintenance of remission in adult EoE patients with the orodispersible budesonide tablet in Germany and other European and non-EU countries. A novel budesonide oral suspension is currently under priority review by the FDA for first approval in the U.S. In contrast, the scientific evidence on the efficacy of proton pump inhibitors remains limited. Moreover, new biologicals have been identified which showed promising results in phase 2 trials and are now being studied in phase 3. This article aims to summarize and discuss recent advances and perspectives in the treatment of EoE.

Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder. Swallowed topical-acting corticosteroids are effective in bringing active EoE into remission. However, it is not clear whether these drugs are effective for long-term maintenance of remission. METHODS: We performed a double-blind trial to compare the efficacy and safety of 2 dosages of a budesonide orodispersible tablet (BOT) vs placebo in maintaining remission of EoE. Maintenance of remission was defined as absence of clinical and histologic relapse and no premature withdrawal for any reason. Two hundred and four adults with EoE in clinical and histologic remission, from 29 European study sites, were randomly assigned to groups given BOT 0.5 mg twice daily (n = 68), BOT 1.0 mg twice daily (n = 68), or placebo twice daily (n = 68) for up to 48 weeks. RESULTS: At end of treatment, 73.5% of patients receiving BOT 0.5 mg twice daily and 75% receiving BOT 1.0 mg twice daily were in persistent remission compared with 4.4% of patients in the placebo group (P < .001 for both comparisons of BOT with placebo). Median time to relapse in the placebo group was 87 days. The frequency of adverse events was similar in the BOT and placebo groups. Morning serum levels of cortisol were in the normal range at baseline and did not significantly change during treatment. Four patients receiving BOT developed asymptomatic, low serum levels of cortisol. Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5 mg group and in 11.8% of patients in the BOT 1.0 mg group; all infections resolved with treatment. CONCLUSIONS: In a phase 3 trial, up to 48 weeks of treatment with BOT (0.5 mg or 1.0 mg twice daily) was superior to placebo in maintaining remission of EoE. Both dosages were equally effective and well tolerated. EudraCT number; 2014-001485-99; ClinicalTrials.gov number, NCT02434029.

Distribution of histopathological features along the colon in microscopic colitis.

PURPOSE: The diagnosis microscopic colitis (MC) consisting of collagenous colitis (CC) and lymphocytic colitis (LC) relies on histological assessment of mucosal biopsies from the colon. The optimal biopsy strategy for reliable diagnosis of MC is controversial. The aim of this study was to evaluate the distribution of histopathological features of MC throughout the colon. METHODS: Mucosal biopsies from multiple colonic segments of patients with MC who participated in one of the three prospective European multicenter trials were analyzed. Histological slides were stained with hematoxylin-and-eosin, a connective tissue stain, and CD3 in selected cases. RESULTS: In total, 255 patients were included, 199 and 56 patients with CC and LC, respectively. Both groups exhibited a gradient with more pronounced inflammation in the lamina propria in the proximal colon compared with the distal colon. Similarly, the thickness of the subepithelial collagenous band in CC showed a gradient with higher values in the proximal colon. The mean number of intraepithelial lymphocytes was > 20 in all colonic segments in patients within both subgroups. Biopsies from 86 to 94% of individual segments were diagnostic, rectum excluded. Biopsies from non-diagnostic segments often showed features of another subgroup of MC. CONCLUSION: Conclusively, although the severity of the histological changes in MC differed in the colonic mucosa, the minimum criteria required for the diagnosis were present in the random biopsies from the majority of segments. Thus, our findings show MC to be a pancolitis, rectum excluded, questioning previously proclaimed patchiness throughout the colon.

[Treatment of IBS with Lactobacillus plantarum 299v: Therapeutic success increases with length of treatment - real-life data of a non-interventional study in Germany]. / Reizdarmbehandlung mit Lactobacillus plantarum 299v: Längere Einnahme verstärkt Behandlungserfolg ­ Ergebnisse einer nichtinterventionellen Studie.

INTRODUCTION: The treatment of irritable bowel syndrome (IBS) in clinical practice is frequently challenging. Modulation of the intestinal microbiome as a treatment option is becoming more and more important. The effectiveness of a bacterial strain, Lactobacillus plantarum 299v (LP299V), was previously investigated in placebo-controlled clinical trials in patients with IBS over 4 weeks. The aims of the present non-interventional study were therefore to investigate tolerability and effectiveness of LP299V under everyday conditions and to gain information on long-term treatment. METHODS: Data on tolerability and effectiveness of LP299V (1 capsule/day; 1 × 1010 CFU) were prospectively collected in 25 centers in 221 patients with IBS. The maximal treatment duration was 12 weeks. The survey was carried out using symptom diaries and medical assessments. Changes in frequency and severity of symptoms were compared to baseline and defined the primary endpoint. RESULTS: During the 12-week treatment, a significant and continuous reduction of overall symptom score (p < 0.05) was observed. In addition, a significant reduction of severity (S) and frequency (H) of individual symptoms, such as abdominal pain (S: - 67 %, H: - 51 %), flatulence (S: - 61 %, H: - 63 %), diarrhea (S: - 70 %, H: - 32 %) and constipation (S: - 79 %, H: - 6 %) was observed. Urgency and feeling of incomplete evacuation were significantly decreased (p < 0.001). Additionally, quality of life increased significantly (mental well-being: + 110 %, influence on everyday life: -67 %, p < 0.01). Self-assessment identified that long-term treatment with LP299V was tolerated well by 94 % of patients. CONCLUSION: In real life, LP299V significantly alleviates the global symptoms of IBS in patients. In order to achieve the maximum effect, long-term use of LP299V (as here 12 weeks) appears to be indicated and is well tolerated.

[Treatment of eosinophilic esophagitis - advancements and perspectives]. / Therapie der eosinophilen Ösophagitis ­ Fortschritte und Perspektiven.

In recent years significant progress has been made in the treatment of eosinophilic esophagitis (EoE), especially in the area of topical corticosteroids. Novel EoE-specific formulations have been developed and first approvals have been obtained for induction and maintenance of remission in adult EoE patients with the orodispersible budesonide tablet in Germany and other European and non-EU countries. A novel budesonide oral suspension is currently under priority review by the FDA for first approval in the U.S. In contrast, the scientific evidence on the efficacy of proton pump inhibitors remains limited. Moreover, new biologicals have been identified which showed promising results in phase 2 trials and are now being studied in phase 3. This article aims to summarize and discuss recent advances and perspectives in the treatment of EoE.

[The gastroenterology during the first and second wave of corona pandemic - two surveys by the working group of the guiding gastroenterologic clinicians (ALGK)]. / Die Gastroenterologie in der ersten und zweiten Corona-Welle ­ zwei Umfragen der Arbeitsgemeinschaft Leitender Gastroenterologischer Krankenhausärzte (ALGK).

BACKGROUND: An evaluation of the non-university hospitals in Germany with regard to the actual and follow-up working condition, alterations and perspectives during the Corona-crisis is missing. The working group of the guiding gastroenterologic clinicians (ALGK) comprises more than 70% of the head physicians of gastroenterological units leading to representative informations. METHODS: The ALGK conducted two surveys among its members in 2020 during the first and 2021 during the second Corona-wave. 369 members with correct email adresses were contacted. The first survey included 17 and the second survey 21 questions. RESULTS: 58 % of the respondent represented primary and standard care hospitals, 36 % secondary care hospitals, 6 % tertiary hospitals of maximum care, 43 % communal, 38 % confessional and 18 % private hospitals. 87 % of the respondent reported about cancellation of the hospital appointments by the patients (87 %/85 %). In the second survey, appointment cancellation by the physican (58 % vs. 84 %), reduction of emergency cases (16 % vs. 29 %), postponement of diagnostic or therapeutic appointments (85 % vs. 99 %) and reduction of programmed inpatient (65 vs. 91 %) or outpatient treatment (15 % vs. 84 %) were lesser compared to the first survey. Mean reduction of endoscopic procedures per unit were 337/month to 151/month (55 %) for diagnostic endoscopy, 174/month to 84/month (52 %) for therapeutic endoscopy and 56/month to 7/month (87,5 %) for prevention colonoscopy. The comparison between hospital operators revealed more reports on staff to be under quarantine, more very strong or strong feeling of psychological stress, more fear of corona-infection and more suspicion of ambulatory maintenance in gastroenterology in private hospitals. Willingness for vaccination was very high among physicians and nursing staff (92 %/89 %) and not different between the hospital operators. 38 % of the repsondent reported on the fear of existential risk of their hospital because of the Corona-crisis. CONCLUSION: The two ALGK surveys give a reprensentative picture of the situation of non-university gastroenterological units during Corona-pandemic in Germany.

[Bile acid diarrhea, stepchild of chronic diarrhea - prevalence, diagnosis and treatment. Update 2021]. / Chologene Diarrhö, Stiefkind der chronischen Diarrhö ­ Prävalenz, Diagnostik und Therapie. Update 2021.

Bile acid diarrhea is one of the most frequently undiagnosed causes of chronic diarrhea. A variety of different pathophysiologic causes can underlie chronic diarrhea. Even after exclusion of the more frequent causes, up to 5 % of the population remains affected by unexplained chronic diarrhea. In up to 50 % within this cohort, bile acid diarrhea is the underlying cause.The various pathophysiologies leading to bile acid diarrhea are well characterized. In this way, bile acid diarrhea can be divided into primary, secondary and tertiary subtypes. Common to all causes is the increased amount of bile acids in the colon and in the faeces and the resulting secretory-osmotic diarrhea, in more severe forms in combination with steatorrhea. The diagnosis of bile acid diarrhea follows a clear algorithm which, in addition to the search for the cause and possibly a therapeutic trial, recognizes the 75SeHCAT test as the reference method for the detection of an increased loss of bile acids. In view of the chronic nature of the symptoms and the need for permanent, lifelong therapy, the use of a one-time, reliable diagnostic test is justified, though the test is currently only available at a few centers. In addition to the treatment of identifiable underlying diseases, the current treatment includes the use of drugs that bind bile acids, with additional nutritional recommendations and vitamin substitutions.The present review article summarizes the pathophysiology and importance of bile acid diarrhea and discusses the current approach towards diagnosis and treatment.

[Quality management in the field of gastroenterology - Proposals of the Quality Commission of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) for Outpatient and Inpatient Quality Assurance]. / Qualität in der Gastroenterologie ­ "Vorschläge der Kommission Qualität der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten zur ambulanten und stationären Qualitätssicherung".

The quality of the medical care depends on numerous factors that can often be influenced by the doctor itself. It is a great challenge to follow the constant scientific progress in practice. Scientific standards in gastroenterology are defined in DGVS guidelines and regularly revised. The implementation of evidence-based recommendations in practice remains challenging. On the basis of the DGVS guidelines, the Quality Commission has therefore developed a selection of quality indicators with particular relevance using standardized criteria, the broad implementation of which could contribute to improved patient care in gastroenterology.

Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial.

BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029.

Use of Evidence-Based Herbal Medicines for Patients with Functional Gastrointestinal Disorders: A Conceptional Framework for Risk-Benefit Assessment and Regulatory Approaches.

BACKGROUND: Herbal or complementary medicines are frequently used for the treatment of patients with functional gastrointestinal disorders (FGID). Regulatory requirements for herbal therapies are inconsistent and, in many jurisdictions, herbal therapies are either self-, minimally- or unregulated. AIM: To provide guidance for the appropriate and safe use of herbal medicines in patients with FGID patients with special consideration of the regulatory frameworks. METHODS: A PubMed search of the literature was performed; relevant articles were included. RESULTS: Similar to chemically defined therapies herbal medicines can cause adverse events. Thus, a risk-benefit appraisal should be undertaken for these therapies. While there is no disease specific mortality in FGID patients, patients with FGID who fail to respond to "empiric" chemically defined therapies undergo diagnostic and therapeutic measures that can be associated with appreciable morbidity and mortality. Thus, effective herbal treatments that subsequently reduce health-care utilization, reduce risks related to diagnostic or therapeutic measures that are initiated if no improvement of symptoms occurs. This "protective" effect of effective treatments for FGID needs to be taken in consideration when the risks and benefits of treatments are determined. In addition, standards that mirror regulations for chemically defined treatments should apply and the components of the respective preparations should undergo ongoing toxicological testing and rigorous quality assurance measures (including pharmacovigilance) applied. CONCLUSIONS: Some herbal therapies offer significant benefits for patients with FGID. To ensure the safety of these treatments, the regulatory requirements should mirror requirements for chemically defined treatments.

Clinical management of eosinophilic esophagitis - a nationwide survey among gastroenterologists in Germany.

BACKGROUND: Eosinophilic esophagitis (EoE) is an increasingly recognized immune-mediated esophageal disease and a common cause for dysphagia and food bolus obstruction. The aim of this study was to evaluate the current clinical management of EoE among adult gastroenterologists in Germany. METHODS: We performed a cross-sectional study of 1393 adult gastroenterologists using a questionnaire containing 22 questions to general, diagnostic, and therapeutic aspects of EoE. The self-administered online survey was conducted between November 2017 and February 2018. Data capture and analysis was performed using SurveyMonkey. RESULTS: The overall responder rate was 29.6 %. More than half of the responders (54.9 %) felt to observe a significant increase of EoE patients. The EREFS score was mostly either unknown (44.3 %) or not routinely used (52.2 %). If EoE was suspected, most responders obtained multiple esophageal biopsies (n = 3 - 4: 35.7 %; n > 4: 61.6 %). The preferred primary treatment was proton pump inhibitors (PPI) in 37.2 % and topical steroids in 35.0 % of responders. PPI regimens were highly diverse, with only half of responders using high-dose PPI regimens. Allergy testing was often initiated (always 25.4 %, sometimes 48.9 %). The most common dietary therapy was 6-food elimination diet (52 %), followed by allergy test-directed diets (16 %) and 2-food elimination diet (16.5 %). The majority of responders indicated a need for long-term treatment (i. e., 23 % of responders in > 50 % their patients and 47.7 % of responders in 25 - 50 % of their patients). CONCLUSIONS: Among gastroenterologists in Germany, substantial variation in the adherence to published EoE guidelines appears to exist. This indicates the need for intensified education and national guidelines in order to optimize and harmonize the clinical management of EoE patients.

Effectiveness of Menthacarin on symptoms of irritable bowel syndrome.

Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common functional gastrointestinal disorders with overlapping symptoms. Effectiveness and safety of Menthacarin (Menthacarin® is the active ingredient of the product Carmenthin® [Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany]) in FD treatment were already demonstrated. We assessed the effectiveness of Menthacarin in reducing concomitant IBS-associated symptoms in FD patients. A systematic search to identify eligible double-blind, randomized controlled trials (RCTs) investigating Menthacarin in FD patients and focusing on IBS-associated symptoms was performed. Three out of five identified RCTs included a total of 111 eligible subjects, which allowed for summary statistics and inclusion into subgroup analysis for FD patients with IBS-associated symptoms. With pain intensity values decreasing by 50-75% on average during 28 days of treatment in patients with accompanying IBS, the subgroup analysis indicates beneficial treatment effects of Menthacarin that are similar to those found for FD patients in the primary analyses. The reduction of IBS-associated symptoms in FD patients suggests Menthacarin as a treatment option for IBS patients.

Dense genotyping of immune-related loci identifies HLA variants associated with increased risk of collagenous colitis.

OBJECTIVE: Collagenous colitis (CC) is a major cause of chronic non-bloody diarrhoea, particularly in the elderly female population. The aetiology of CC is unknown, and still poor is the understanding of its pathogenesis. This possibly involves dysregulated inflammation and immune-mediated reactions in genetically predisposed individuals, but the contribution of genetic factors to CC is underinvestigated. We systematically tested immune-related genes known to impact the risk of several autoimmune diseases for their potential CC-predisposing role. DESIGN: Three independent cohorts of histologically confirmed CC cases (N=314) and controls (N=4299) from Sweden and Germany were included in a 2-step association analysis. Immunochip and targeted single nucleotide polymorphism (SNP) genotype data were produced, respectively, for discovery and replication purposes. Classical human leucocyte antigen (HLA) variants at 2-digit and 4-digit resolution were obtained via imputation from single marker genotypes. SNPs and HLA variants passing quality control filters were tested for association with CC with logistic regression adjusting for age, sex and country of origin. RESULTS: Forty-two markers gave rise to genome-wide significant association signals, all contained within the HLA region on chromosome 6 (best p=4.2×10-10 for SNP rs4143332). Among the HLA variants, most pronounced risk effects were observed for 8.1 haplotype alleles including DQ2.5, which was targeted and confirmed in the replication data set (p=2.3×10-11; OR=2.06; 95% CI (1.67 to 2.55) in the combined analysis). CONCLUSIONS: HLA genotype associates with CC, thus implicating HLA-related immune mechanisms in its pathogenesis.

Modulation of gastrointestinal motility beyond metoclopramide and domperidone : Pharmacological and clinical evidence for phytotherapy in functional gastrointestinal disorders.

The prokinetic cisapride, an important therapeutic option in functional gastrointestinal (GI) disorders, was withdrawn from the market 15 years ago due to rare severe side effects. Likewise in 2014, the use of metoclopramide (MCP) and domperidone in functional GI disorders (FGID) was restricted, consequently leaving a therapeutic gap in clinical practice. A systematic review revealed that the herbal medicinal product (HMP) STW 5 presents a therapeutic option equivalent to MCP and cisapride. STW 5 is the only HMP for which efficacy has been shown in randomized controlled clinical trials (RCTs) in functional dyspepsia and irritable bowel syndrome, based on its multitarget effect on numerous etiological factors. Due to an outstanding favorable safety profile, STW 5 allows an effective and safe use in FGID without a limitation of the duration of the treatment.

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/mm(2 )hpf). Secondary end points included endoscopy score, dysphagia score, drug safety and patient's 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. CLINICALTRIALSGOV NUMBER: NCT02280616; EudraCT number, 2009-016692-29.

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.