Maintenance Of Remission In Ulcerative Colitis Research Articles

Prebiotics for Induction and Maintenance of Remission in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

Prebiotics are nondigestible carbohydrates fermented by gut bacteria into metabolites that confer health benefits. However, evidence on their role for inflammatory bowel disease (IBD) is unclear. This study systematically evaluated the research on prebiotics for treatment of IBD. A search was performed in PubMed, Embase, Cochrane, and Web of Science. Eligible articles included randomized controlled trials or prospective observational studies that compared a prebiotic with a placebo or lower-dose control in patients with IBD. Meta-analyses were performed using random-effects models for the outcomes of clinical remission, clinical relapse, and adverse events. Seventeen studies were included. For induction of clinical remission in ulcerative colitis (UC), the fructooligosaccharide (FOS) kestose was effective (relative risk, 2.75, 95% confidence interval, 1.05-7.20; n = 40), but oligofructose-enriched inulin (OF-IN) and lactulose were not. For maintenance of remission in UC, germinated barley foodstuff trended toward preventing clinical relapse (relative risk, 0.40; 95% confidence interval, 0.15-1.03; n = 59), but OF-IN, oat bran, and Plantago ovata did not. For Crohn's disease, OF-IN and lactulose were no different than controls for induction of remission, and FOS was no different than controls for maintenance of remission. Flatulence and bloating were more common with OF-IN; reported adverse events were otherwise similar to controls for other prebiotics. Prebiotics, particularly FOS and germinated barley foodstuff, show potential as effective and safe dietary supplements for induction and maintenance of remission in UC, respectively. The overall certainty of evidence was very low. There would be benefit in further investigation on the role of prebiotics as treatment adjuncts for IBD.

Fecal transplantation for treatment of inflammatory bowel disease.

Fecal transplantation for treatment of inflammatory bowel disease.

Tofacitinib and newer JAK inhibitors in inflammatory bowel disease-where we are and where we are going.

Inflammatory bowel diseases, comprising ulcerative colitis (UC) and Crohn’s disease, are chronic, immune-mediated and progressive inflammatory disorders affecting the gastrointestinal tract. Tofacitinib is the first oral small-molecule Janus kinase (JAK) inhibitor licensed and approved by the National Institute for Health and Care Excellence (NICE) for use in moderately-to-severely active UC after intolerance, inadequate response, or loss of response to conventional treatment or biologic therapy. The pivotal OCTAVE studies demonstrated the efficacy and safety of tofacitinib for the induction and maintenance of remission in UC. A growing body of evidence from real-world data supports the positive clinical and endoscopic benefits observed with tofacitinib treatment in the OCTAVE trials. This narrative review summarizes the current literature regarding the mechanism of action of tofacitinib, data from registrational trials, emerging real-world evidence, and an overview of the most recent safety evidence. We explore evolving treatment paradigms, including the use of tofacitinib in the COVID-19 era, pregnancy and extraintestinal manifestations, as well as the emerging concept of combining tofacitinib with biological therapy. We will also present a brief overview of the next generation of JAK inhibitors in the pipeline.

Influence of Corticosteroid Use on Short- and Long-Term Outcomes of Biologic Therapy for Inflammatory Bowel Diseases.

Corticosteroids (CS) are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC), but are not recommended as maintenance therapy. Biologic drugs are widely used as an alternative to or in conjunction with CS to induce and maintain remission. This meta-analysis tested the hypothesis that CS use is associated with differential response to biologics. We identified published placebo-controlled clinical trials of biologic drugs approved for the treatment of CD or UC. Pooled estimates of the risk difference (RD) and 95% confidence intervals were derived from random effects models for induction of response and remission and maintenance of remission comparing biologic with CS versus biologic alone. Heterogeneity of response was estimated using I2. Fifteen studies met the inclusion criteria. Pooled estimates of the RD and I2 comparing biologic plus CS versus biologic alone were as follows: induction of UC response 0.15 (0.05, 0.25), I2 = 57.29% and CD response 0.02 (- 0.03, 0.06), I2 = 0.01%; induction of UC remission 0.03 (- 0.01, 0.08), I2 = 0.00% and CD remission 0.08(0.02, 0.14), I2 = 7.81%; and maintenance of UC remission - 0.06 (- 0.13, 0.01), I2 = 0.00% and CD remission - 0.06 (- 0.14, 0.03), I2 = 11.24%. Patients in the placebo arm of CD trials who were receiving CS were less likely to achieve remission during the induction phase (pooled RD - 0.05 (- 0.09, - 0.00), I2 = 0.00%). In this meta-analysis of placebo-controlled trials, CS use was associated with higher biologic response rates for UC and remission rates for CD during the induction phase, but were not associated with improved maintenance of remission.

Long-term, Real-life, Observational Study in Treating Outpatient Ulcerative Colitis with Golimumab

Several studies have found Golimumab (GOL) effective and safe in the short-term treatment of ulcerative colitis (UC), but few long-term data are currently available from real world. Our aim was to assess the long-term real-life efficacy and safety of GOL in managing UC outpatients in Italy. A retrospective multicenter study assessing consecutive UC outpatients treated with GOL for at least 3-month of follow-up was made. Primary endpoints were the induction and maintenance of remission in UC, defined as Mayo score ≤2. Several secondary endpoints, including clinical response, colectomy rate, steroid free remission and mucosal healing, were also assessed during the follow-up. One hundred and seventy-eight patients were enrolled and followed up for a median (IQR) time of 9 (3-18) months (mean time follow-up: 33.1±13 months). Clinical remission was achieved in 57 (32.1%) patients: these patients continued with GOL, but only 6 patients (3.4%) were still under clinical remission with GOL at the 42nd month of follow-up. Clinical response occurred in 64 (36.4%) patients; colectomy was performed in 8 (7.8%) patients, all of them having primary failure. Steroid-free remission occurred in 23 (12.9%) patients, and mucosal healing was achieved in 29/89 (32.6%) patients. Adverse events occurred in 14 (7.9%) patients. Golimumab does not seem able to maintain long-term remission in UC in real life. The safety profile was good.

Treatment of inflammatory bowel diseases: focusing on 5-aminosalicylates and immunomodulators

Background: Recently, the incidence and prevalence rates of inflammatory bowel disease (IBD) have increased worldwide, including in Korea. Although there has been considerable progress in the management of IBD following the discovery of biologic agents, 5-aminosalicylate (5-ASA) and immunomodulators are still considered cornerstones in the management of mild to moderate IBD.Current Concepts: 5-ASA plays a key role in inducing remission in patients with mild to moderate ulcerative colitis. High doses of 5-ASA are more effective in inducing remission in patients with moderate ulcerative colitis, and combination therapy of oral 5-ASA and topical 5-ASA agents is recommended. Although the effect of 5-ASA in patients with Crohn disease is limited, high doses of 5-ASA can be effective for patients with mild disease, inflammatory behavior, and colonic involvement. Maintaining remission is essential for patients with IBD. Good doctor-patient relationships and encouraging drug adherence are recommended. Regarding drug adherence, a once-daily regimen is preferred for patients’ satisfaction. Thiopurines, the most important immunomodulators, show therapeutic benefits, such as steroid-sparing effects and remission maintenance in ulcerative colitis and Crohn disease after induction therapy. However, several side effects, including severe leukopenia, can induce the discontinuation of thiopurines. Close monitoring and management decisions should be individualized according to the risk of relapse and adverse events.Discussion and Conclusion: In conclusion, 5-ASA and immunomodulators are cornerstones in the management of IBD. As such, clinicians should have knowledge of these drugs and patients’ characteristics for proper prescription.

A ‘real‐world’ retrospective multi‐centre cohort study comparing infliximab and adalimumab for the maintenance of remission in ulcerative colitis

Background Anti-tumour necrosis factor therapy is an established treatment for moderate-to-severely active ulcerative colitis (UC). Recent network meta-analyses of controlled trial data have indicated a superiority of intravenous drugs (infliximab) over subcutaneous (adalimumab). We conducted a retrospective multi-centre cohort study to determine the comparative effectiveness of these two drugs. Methods Patients with UC administered infliximab or adalimumab as their first biologic, identified from the therapy databases of five UK hospitals, were included, if they had completed induction and were on maintenance treatment. Patients receiving infliximab as ‘rescue’ therapy for acute severe UC were excluded. The primary end-points for comparison were the number of patients remaining on initial therapy (infliximab or adalimumab) at 52 weeks and the number of patients in clinical remission at 52 weeks (Simple Clinical Colitis Activity [SCCAI] score ≤ 3). Results Seventy-eight infliximab and 63 adalimumab patients were analysed. At 52 weeks, 83% of infliximab patients and 59% of adalimumab patients remained on therapy (P = 0.001). At 52 weeks, 62% of the infliximab group were in clinical remission compared to 32% of the adalimumab group (P = 0.0004). Primary non-response was reported in 24% of adalimumab patients and 5% of infliximab patients (P = 0.001). There were no significant differences in colectomy rates or hospital admission for acute flares at 52 weeks. Conclusions Our real-world results affirm the findings of network meta-analyses of clinical trials, suggesting that infliximab is superior to adalimumab in the maintenance of remission in UC up to 52 weeks.

Prebiotics and Probiotics in Inflammatory Bowel Disease: Where are we now and where are we going?

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn's disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms "prebiotics AND ulcerative colitis", "probiotics AND ulcerative colitis", "prebiotics AND Crohn's disease", "probiotics AND Crohn's disease", "probiotics AND acute pouchitis", "probiotics AND chronic pouchitis" and "prebiotics AND pouchitis". Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.

P002 The use of probiotics in the maintenance of remission in ulcerative colitis: A systematic review

BACKGROUND: Ulcerative colitis (UC) is a chronic relapsing disease characterised by diffuse mucosal inflammation limited to the colon. Current maintenance treatments have multiple adverse events and an effective treatment with minimal adverse events is desired. Several studies have demonstrated the importance of intestinal flora in the pathogenesis of ulcerative colitis. It has been suggested that modifying the bacteria flora with probiotics may attenuate the inflammatory process and prevent relapses in UC. METHODS: Data extraction and risk of bias assessment of included studies were independently performed by 2 authors, data was analysed using Review Manager 5.3, dichotomous and continuous outcomes were expressed as risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). The certainty of evidence was assessed using GRADE methodology. RESULTS: Eleven studies (1,204 randomised participants) met the inclusion criteria. The studies compared probiotics to placebo, probiotics to 5-ASA and a combination of probiotics and 5-ASA to 5-ASA. The risk of bias was high in all except 3 studies due to selective reporting, incomplete outcome data and lack of blinding, this results in low to very low rating of the quality of the evidence. There is no clear difference in relapse when probiotics are compared with placebo (RR, 0.86; 95% CI, 0.71–1.04; 341 participants, 5 studies; low quality of evidence). There is no clear difference in maintenance of remission when probiotics are compared with 5-ASA (RR, 1.05; 95% CI, 0.89–1.24; 122 participants; 2 studies; low quality of evidence). There is no clear difference in maintenance of remission when probiotics coupled with—ASA are compared to 5-ASA alone (RR, 1.49; 95% CI, 0.86–2.57; 92 participants; 2 studies; very low quality evidence). CONCLUSION(S): Given the limited data and high risk of bias in the included studies, there is insufficient evidence to make conclusion about the efficacy of probiotics for maintenance of remission in UC. This is based on low to very low quality of evidence. This review highlights the need for further well-designed randomised controlled trials (RCT) to investigate the above objective. Future research should focus on comparing probiotics with 5-ASA as this will reflect clinical practise, patients are unlikely to not be on any treatment to maintain remission. Additionally, length of follow up of most studies in this review is much less than other published reviews, studies looking at 12 months or less are simply too limited in their usefulness to clinical practise. Overall this is the second review for the above objective and it is surprising to see that similar issues exist that did in the first review such as small participants numbers. The issues highlighted in this review should be taken into account for any authors that wish to produce well-designed RTCS looking at the usefulness of probiotics for patients with UC. Some staff received funding from NIHR Cochrane programme.

P053 TARGETED RELEASE ORAL CYCLOSPORINE FORMULATION AS A POTENTIAL NEW THERAPY FOR ULCERATIVE COLITIS

Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa. Infliximab has long been a standard therapy for moderate to severe UC. IV followed by oral cyclosporine (CsA) has demonstrated similar safety and efficacy to infliximab for the treatment of acute UC; however, prolonged use for the maintenance of remission is limited due to concerns about side effects of systemically available CsA. There remains a need for an oral CsA therapy that controls UC disease activity while minimizing systemic exposure. ST-0529 is a novel, orally administrated, solubilized CsA formulation designed to optimize the delivery of drug to colonic tissue while minimizing systemic absorption. To characterize the whole blood pharmacokinetics of ST-0529 following single and multiple oral doses (ODs), and compare to the pharmacokinetic profile following CsA IV infusion in healthy male subjects. To establish CsA colonic mucosa concentrations following single or twice-daily (BID) ODs and various dosage regimens of ST-0529 for seven days, comparing them to CsA continuous IV infusion. In Stage 1, a total of 24 eligible healthy male subjects received either 2 mg/kg/day of IV CsA over two consecutive 12-hour infusions (per protocol) and a once- or a twice-daily ODs of 75 mg ST-0529 for seven days. The protocol allowed to conduct further investigations with alternative ST-0529 doses and dose frequencies after review of Stage 1 data. Following this review, eight subjects recruited to Stage 2 received 37.5mg ST-0529 once-daily orally for seven days. A further eight subjects recruited to Stage 3 received 150mg ST-0529 BID ODs for seven days. Single dose systemic exposure to CsA was considerably lower (~5%) following treatment with ST-0529 ranging from 37.5 mg to 300 mg daily for seven days compared with 24-hour continuous IV 2 mg/kg/day infusion. All ST-0529 dosage groups tested achieved colon tissue concentrations comparable to or above that attained during IV CsA administration with the 75 mg BID and 150 mg BID groups sustaining the minimum tissue concentrations achieved following IV infusion and being substantially higher than that achieved by 37.5 mg OD and 75 mg OD groups. A total of 26 subjects (54.2%) reported treatment-emergent adverse events (TEAEs) during the study. All were mild or moderate; there were no severe TEAEs reported. The study demonstrated ST-0529 achieved similar or higher colonic tissue concentrations than continuous IV CsA infusion with substantially lower systemic exposure. These data suggest that ST-0529 may provide similar or enhanced efficacy to IV or oral CsA formulations with an improved tolerance profile and thus support further development as a treatment for the induction and maintenance of remission in UC. Mean CsA concentrations and AEs Mean CsA concentrations and AEs

Fecal transplantation for treatment of inflammatory bowel disease.

Fecal transplantation for treatment of inflammatory bowel disease.

Cannabis for the treatment of ulcerative colitis.

Cannabis for the treatment of ulcerative colitis.

Ethnic and Demographic Differences in Colectomy Rates and Timing for Ulcerative Colitis: 2007-2014

Introduction: Ulcerative Colitis (UC) is a chronic inflammatory disease of the bowel, with one third of patients requiring a colectomy for fulminant disease and tissue dysplasia. In 2007, infliximab was approved for induction and maintenance of remission in UC, with some evidence to suggest a potential reduction in colectomies. The aim of this study is to examine relative colectomy rates for UC among different ethnicities from 2007 to 2014 in order to evaluate for development of new trends or disparities. Methods: The data source was the NIS database, from 2007 to 2014. Patients aged 5 years and older with a primary diagnosis of UC were used. Additional variables included race, age, gender, insurance coverage, region, hospital teaching status, hospital size, elective admission status, and zip code income quartile. Odds ratios for colectomy were calculated via logistic regression. Negative binomial regression modeling was used to observe associations between variables and time to colectomy. Results: Compared to Whites, the odds ratios of colectomy for Blacks (0.63, 95% C.I. 0.53-0.749, p<0.01), Hispanics (0.729, 95% C.I. 0.630-0.844, p< 0.01), and Asians (0.332, 95% C.I. 0.219-0.504, p< 0.01) were all significantly lower. However, Black (2.024, 95% C.I. 1.614-2.537, p< 0.01), Hispanic (1.295, 95% C.I. 1.078-1.557, p< 0.01), and Asian ethnicity (4.293, 95% C.I. 2.632-7.002, p< 0.01) were associated with increasing time until receipt of colectomy. Private insurance was associated with higher colectomy rates (1.545, 95% C.I. 1.325-1.802, p< 0.01), as was increasing hospital zip code income quartile (1.085, 95% C.I. 1.048-1.124, p< 0.01). Conclusion: Discrepancies in colectomy rates and timing are seen in our models which mirror closely findings in a prior study from 1999-2003 (Nguyen GC, et al. Racial and Geographic Variations in Colectomy Rates Among Hospitalized Ulcerative Colitis Patients. Clinical Gastroenterology and Hepatology 2006; 4: 1507-1513.e1). The consistency between our findings suggests that the availability of infliximab has not altered the relative differences in surgical management of inpatients of different ethnicities with UC flares. Closer study of utilization and response to UC therapy across ethnic and demographic lines is needed to better elucidate whether such practices are based on true phenotypic differences in disease or bias, as it appears white, wealthier patients continue to more readily and rapidly receive colectomies.598_A Figure 1. Number of Colectomies by Variable.598_B Figure 2. Colectomy Odds Ratios.598_C Figure 3. Negative Binomial Regression Analysis for Time to Colectomy.

Effectiveness and safety of adalimumab to treat outpatient ulcerative colitis: A real-life multicenter, observational study in primary inflammatory bowel disease centers.

Adalimumab (ADA) was approved in Italy for the treatment of ulcerative colitis (UC) unresponsive to standard treatments in 2014, but no data from real life are currently available. The aim of the present study was to assess the real-life efficacy and safety of ADA in managing UC outpatients in some Italian primary inflammatory bowel disease (IBD) centers after approval of ADA reimbursement.Consecutive UC outpatients with at least 3-month follow-up were retrospectively evaluated. The primary end point was the induction and maintenance of remission in UC, defined as Mayo score ≤2.One hundred seven patients were included. At 3-month follow-up, obtained in 102 (95.3%) patients, 56 (54.9%) patients achieved a clinical remission. At univariate analysis, both Mayo partial score >7 and Mayo subscore for endoscopy = 3 at entry showed to be significantly associated with the lack of remission induction.During a median (95% confidence interval [CI]) follow-up of 18 (12–24) months, 56.6% of patients were under clinical remission; clinical response was achieved in 89.2% of cases. Mucosal healing was achieved in 66 (76.7%) patients, and colectomy occurred in 3 (2.8%) patients. Both C-reactive protein and fecal calprotectin values significantly decreased during follow-up. Steroids discontinuation occurred in 67 (66.7%) patients, and ADA dose escalation was adopted in 9 (16.1%) patients under remission. No factor was significantly related to the maintenance of clinical remission.This first Italian experience found ADA safe and effective to induce and maintain remission in real-life UC outpatients.

Effectiveness and Safety of Golimumab in Treating Outpatient Ulcerative Colitis: A Real-Life Prospective, Multicentre, Observational Study in Primary Inflammatory Bowel Diseases Centers.

Golimumab (GOL) has been recently approved in Italy for the treatment of ulcerative colitis (UC) unresponsive to standard treatments. Our aims were to assess the real-life efficacy and safety of GOL in managing UC outpatients in Italian primary Inflammatory Bowel Diseases (IBD) centres. Consecutive UC outpatients with at least 3-months follow-up were enrolled. Primary end-point was the induction and maintenance of remission in UC, defined as Mayo score </=2, at 6-month follow-up. Ninety-three patients were enrolled. At 6-month follow-up, remission was obtained in 34 (36.5%) patients. Shorter duration of disease was the only significant predictive factor of remission. Clinical response was achieved in 60 (64.5%) patients, while mucosal healing (MH) was obtained in 18 (19.3%) patients. Sixteen (47.0%) patients under remission were still under therapy with steroids. C-reactive protein and fecal calprotectin significantly dropped during the follow-up (plt;0.001 for both proteins). Adverse events occurred in 4 (4.3%) patients and 3 of them stopped treatment. Colectomy was performed in only one patient (1.1%). Golimumab seems to be safe and effective in inducing and maintaining remission in real life UC outpatients.

Fecal transplantation for treatment of inflammatory bowel disease

Fecal transplantation for treatment of inflammatory bowel disease

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.

P-054 Probiotics for Maintenance of Remission in Ulcerative Colitis

Background: Ulcerative colitis (UC) is a chronic relapsing disease characterised by diffuse mucosal inflammation of the colon. Current maintenance treatments have multiple adverse events and an effective treatment with minimal adverse events is desired. Several studies have demonstrated the importance of intestinal flora in the pathogenesis of ulcerative colitis. It has been suggested that modifying the bacterial flora with probiotics may attenuate the inflammatory process and prevent relapses in ulcerative colitis. Five years ago, a Cochrane review found only 4 studies and no evidence regarding the efficacy of probiotics, but much work has been published in recent years. An up to date Cochrane systematic review was performed to determine the efficacy and safety of probiotics for the maintenance of remission in ulcerative colitis. Methods: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and the Cochrane Inflammatory Bowel Disease Group Specialised Trial Register were searched (Inception-January 2015). Manufacturers of probiotics were contacted to identify any unpublished trials. References of trials were also searched for any additional trials. Abstracts were considered for inclusion if full details to judge inclusion and risk of bias were offered or available from the authors. Randomised controlled trials (RCTs) that compared probiotics against placebo or any other intervention for the maintenance of remission in ulcerative colitis were eligible for inclusion. Data extraction and assessment of methodological quality of included studies were independently performed by 2 authors. The main outcome measure was the occurrence of clinical or endoscopic relapse. Results: The search yielded 1006 results, with 34 papers screened in full. Seven studies (n = 887) met the inclusion criteria and were included in the review. Four trials compared probiotics to mesalazine and 3 trials compared probiotics with placebo. The studies ranged in length from 3 to 12 months. The risk of bias was low for randomisation and allocation concealment in one study and unclear in the others. One study was open label, the rest rated as low risk for blinding as double-blinded double dummy trials. The risk of bias was high in one study due to incomplete outcome data and 2 studies due to selective reporting, all the remaining studies low risk. There was no statistically significant difference between probiotics and placebo for maintenance of remission in UC, although there were just 2 small studies with 92 participants (Odds Ratio 0.56; 95% CI 0.22-1.40). Meta-analysis of 4 studies (n = 638) found no statistically significant difference between probiotics and mesalazine (OR 1.29; 95% CI 0.92-1.80). There was no statistically significant difference in the incidence of adverse events (OR 1.16; 95% CI 0.79-1.71). Conclusions: There was no statistically significant difference between probiotics and placebo, although there were just 2 small studies in the pooled analysis at some risk of bias. There was no difference in efficacy found between probiotics and mesalazine on pooled analysis and no difference in adverse events. Further research is proposed to investigate the role of probiotics to maintain remission in UC.

Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease.

BackgroundProbiotics are microorganisms that are ingested either in combination or as a single organism in an effort to normalize intestinal microbiota and potentially improve intestinal barrier function. Recent evidence has suggested that inflammatory bowel disease (IBD) may result from an inappropriate immunologic response to intestinal bacteria and a disruption in the balance of the gastrointestinal microbiota in genetically susceptible individuals. Prebiotics, synbiotics, and probiotics have all been studied with growing interest as adjuncts to standard therapies for IBD. In general, probiotics have been shown to be well-tolerated with few side effects, making them a potential attractive treatment option in the management of IBD.AimTo perform a systematic review of randomized controlled trials on the use of probiotics, prebiotics, and synbiotics in IBD.ResultsIn our systematic review we found 14 studies in patients with Crohn’s disease (CD), 21 studies in patients with ulcerative colitis (UC), and five studies in patients with pouchitis. These were randomized controlled trials using probiotics, prebiotics, and/or synbiotics. In patients with CD, multiple studies comparing probiotics and placebo showed no significant difference in clinical outcomes. Adding a probiotic to conventional treatment improved the overall induction of remission rates among patients with UC. There was also a similar benefit in maintaining remission in UC. Probiotics have also shown some efficacy in the treatment of pouchitis after antibiotic-induced remission.ConclusionsTo date, there is insufficient data to recommend probiotics for use in CD. There is evidence to support the use of probiotics for induction and maintenance of remission in UC and pouchitis. Future quality studies are needed to confirm whether probiotics, prebiotics, and synbiotics have a definite role in induction or maintenance of remission in CD, UC, and pouchitis. Similar to probiotics, fecal microbiota transplantation provides an alternate modality of therapy to treat IBD by influencing the intestinal flora.

Effect of MMX® mesalamine coadministration on the pharmacokinetics of amoxicillin, ciprofloxacin XR, metronidazole, and sulfamethoxazole: results from four randomized clinical trials.

BackgroundMMX® mesalamine is a once daily oral 5-aminosalicylic acid formulation, effective in induction and maintenance of ulcerative colitis remission. Patients on long-term mesalamine maintenance may occasionally require concomitant antibiotic treatment for unrelated infections.AimTo evaluate the potential for pharmacokinetic interactions between MMX mesalamine and amoxicillin, ciprofloxacin extended release (XR), metronidazole, or sulfamethoxazole in four open-label, randomized, placebo-controlled, two-period crossover studies.MethodsIn all four studies, healthy adults received placebo once daily or MMX mesalamine 4.8 g once daily on days 1–4 in one of two treatment sequences. In studies 1 and 2, subjects also received a single dose of amoxicillin 500 mg (N=62) or ciprofloxacin XR 500 mg (N=30) on day 4. In studies 3 and 4, subjects received metronidazole 750 mg twice daily on days 1–3 and once on day 4 (N=30); or sulfamethoxazole 800 mg/trimethoprim 160 mg twice daily on days 1–3 and once on day 4 (N=44).ResultsMMX mesalamine had no significant effects on systemic exposure to amoxicillin, ciprofloxacin, or metronidazole; the 90% confidence intervals (CIs) around the geometric mean ratios (antibiotic + MMX mesalamine: antibiotic + placebo) for maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) fell within the predefined equivalence range (0.80–1.25). Sulfamethoxazole exposure increased by a statistically significant amount when coadministered with MMX mesalamine; however, increased exposure (by 12% in Cmax at steady state; by 15% in AUC at steady state) was not considered clinically significant, as the 90% CIs for each point estimate fell entirely within the predefined equivalence range. Adverse events in all studies were generally mild.ConclusionMMX mesalamine may be coadministered with amoxicillin, ciprofloxacin, metronidazole, or sulfamethoxazole, without affecting pharmacokinetics or safety of these antibiotics.ClinicalTrials.gov identifiersNCT01442688, NCT01402947, NCT01418365, and NCT01469637.