5-ASA Use Research Articles

The gap between scientific evidence and clinical practice: 5-aminosalicylates are frequently used for the treatment of Crohn's disease.

There is uncertain evidence of effectiveness of 5-aminosalicylates (5-ASA) to induce and maintain response and remission of active Crohn's disease (CD), and weak evidence to support their use in post-operative CD. To assess the frequency and determinants of 5-ASA use in CD patients and to evaluate the physicians' perception of clinical response and side effects to 5-ASA. Data from the Swiss Inflammatory Bowel Disease Cohort, which collects data since 2006 on a large sample of IBD patients, were analysed. Information from questionnaires regarding utilisation of treatments and perception of response to 5-ASA were evaluated. Logistic regression modelling was performed to identify factors associated with 5-ASA use. Of 1420 CD patients, 835 (59%) were ever treated with 5-ASA from diagnosis to latest follow-up. Disease duration >10 years and colonic location were both significantly associated with 5-ASA use. 5-ASA treatment was judged to be successful in 46% (378/825) of treatment episodes (physician global assessment). Side effects prompting stop of therapy were found in 12% (98/825) episodes in which 5-ASA had been stopped. 5-Aminosalicylates were frequently prescribed in patients with Crohn's disease in the Swiss IBD cohort. This observation stands in contrast to the scientific evidence demonstrating a very limited role of 5-ASA compounds in the treatment of Crohn's disease.

PWE-118 Predictors Of Colectomy And The Impact Of Thiopurines On The Risk Of Colectomy In Ulcerative Colitis – A National Uk Based Observational Study

IntroductionThiopurines (TPs) including azathioprine and mercaptopurine have an established role in maintaining disease remission in ulcerative colitis (UC) but their impact on the risk of colectomy remains unknown. Our aim...

Safety of 5-Aminosalicylic Acid Derivatives in Patients with Sensitivity to Acetylsalicylic Acid and Nonsteroidal Anti-inflammatory Drugs

One of the cornerstones of the management of inflammatory bowel disease is the use of 5-aminosalicylic acid (5-ASA) compounds for treatment of flares and as maintenance therapy during remission. There are concerns about using 5-ASA in patients with a history of hypersensitivity to acetylsalicylic acid (ASA). To assess the literature with respect to the safety of 5-ASA compounds in patients with documented sensitivity to ASA or nonsteroidal anti-inflammatory drugs (NSAIDs). A literature search was conducted in the MEDLINE and Embase databases, using various search terms, including "aminosalicylic acids", "non-steroidal anti-inflammatory agents," "hypersensitivity", and "allergy". The search was limited to articles (of any study design) published in English. Abstracts, full articles, and reference lists from retrieved articles were assessed to identify further relevant literature. Of 485 citations identified in the initial search, 4 case reports were relevant to the study objective and were analyzed in detail. Three of the case reports described the successful use of 5-ASA compounds in patients with prior sensitivity to ASA or an NSAID. The fourth report described a reaction to 5-ASA in a patient who had previously tolerated ASA. All of the reports were limited by lack of investigation into the validity of the reported sensitivity to ASA or 5-ASA. There is a dearth of evidence demonstrating cross-reactivity between ASA or NSAID and 5-ASA. This lack of information may relate to the mechanism of action of 5-ASA. This agent controls inflammation by inhibiting prostaglandin E2 and leukotrienes. In contrast, ASA-induced or NSAID-induced reactions are due to inhibition of the cycloxygenase-1 enzyme and subsequent release of histamine and synthesis of leukotrienes. Further reports describing the safety of 5-ASA use in patients with sensitivity to ASA or NSAIDs are needed before safety in this situation can be definitively determined. In patients with sensitivity to ASA or NSAID who require 5-ASA, a test dose of 5-ASA (to rule out potential cross-reactivity) or further investigation of the ASA or NSAID sensitivity is recommended.

Maternal use of 5-aminosalicylates in early pregnancy and congenital malformation risk in the offspring

Objective. Most previous studies have failed to demonstrate any effect of maternal use of 5-aminosalicylates (5-ASA) on malformation risk, but the number of infants studied have, in most cases, been low. The objective of the study was to get data from a large study with prospectively ascertained exposure information. Material and methods. The study was based on data in the Swedish Medical Birth Register (1996–2011) where identification of maternal drug use is made from midwife interviews in early pregnancy. The presence of congenital malformations was ascertained from three national registers. Adjusted odds ratios were calculated by the Mantel-Haenszel methodology. Results. Among 1,552,109 women, 3651 with 3721 infants had reported the use of 5-ASAs in early pregnancy. The risk of a major malformation was increased (1.37, 95% confidence interval = 1.17–1.62) and still more for a cardiovascular defect (1.74, 1.37–2.22). This effect seemed to be influenced by concomitant use of systemic glucocorticosteroids or immunosuppressants but some confounding by indication may also exist. There was no marked difference between the four 5-ASA drugs studied. Conclusions. Infants born of women who use 5-ASA drugs in early pregnancy have an increased risk of a congenital malformation, notably a cardiovascular defect. This could be a drug effect or an effect of an active inflammatory bowel disease.

Managing Ulcerative Colitis: The Guidelines and Beyond

Management guidelines offer clinicians clear, evidence-based and often succinct treatment advice. For ulcerative colitis these guidelines describe the use of 5-ASA, corticosteroids, thiopurines, cyclosporine, and anti-TNFα therapies. However, guidelines do have some drawbacks, mainly a lack of concrete advice concerning patients resistant to these aforementioned therapies. This review gives a short overview of current guidelines and addresses treatment alternatives for conventional therapies.

Racial and Ethnic Differences in Health Care Utilization and Outcomes Among Ulcerative Colitis Patients in an Integrated Health-Care Organization

Current knowledge of racial disparities in healthcare utilization and disease outcomes for ulcerative colitis (UC) is limited. We sought to investigate these differences among Caucasian, African American, Asian, and Hispanic patients with ulcerative colitis in Kaiser Permanente, a large integrated health-care system in Northern California. This retrospective cohort study used computerized clinical data from 5,196 Caucasians, 387 African-Americans, 550 Asians, and 801 Hispanics with prevalent UC identified between 1996 and 2007. Healthcare utilization and outcomes were compared at one and five-year follow-up by use of multivariate logistic regression analysis. Compared with whites, the male-to-female ratio differed for African-Americans (0.68 vs. 0.91, p<0.01) and Asians (1.3 vs. 0.91, p<0.01). Asians had fewer co-morbid conditions (p<0.01) than whites, whereas more African-Americans had hypertension and asthma (p<0.01). Use of immunomodulators did not differ significantly among race and/or ethnic groups. Among Asians, 5-ASA use was highest (p<0.05) and the incidence of surgery was lowest (p<0.01). Prolonged steroid exposure was more common among Hispanics (p<0.05 at 1-year) who also had more UC-related surgery (p<0.01 at 5-year) and hospitalization (<0.05 at 5-year), although these differences were not significant in multivariate analysis. In this population of UC patients with good access to care, overall health-care utilization patterns and clinical outcomes were similar across races and ethnicity. Asians may have milder disease than other races whereas Hispanics had a trend toward more aggressive disease, although the differences we observed were modest. These differences may be related to biological factors or different treatment preferences.

Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979–2011

IntroductionTreatment possibilities have changed in inflammatory bowel disease (IBD). We assessed changes in medical treatment and surgery over time and impact of medications on risk of surgery in a population-based...

The fate of indefinite and low-grade dysplasia in ulcerative colitis and primary sclerosing cholangitis colitis before and after liver transplantation

Patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at an increased risk of colorectal neoplasia, but it is unknown if liver transplantation (LT) alters neoplasia progression. To examine the natural history of indefinite dysplasia (IND) and low-grade dysplasia (LGD) that develop in patients with PSC-UC with and without LT. We performed a retrospective review of patients with PSC and UC evaluated at our institution between 1993 and 2011 who were diagnosed with IND or LGD before or after LT for PSC. The primary end point was neoplasia progression or persistent LGD. Ninety-six patients (non-LT n = 63, LT n = 33) were examined. For the IND group, multifocal lesions were significantly associated with time to neoplasia progression [hazard ratio (HR), 3.5; 95% confidence interval (CI), 1.3-9.7], while 5-aminosalicylate (5-ASA) use was protective (HR, 0.2; 95% CI, 0.1-0.6). For patients with LGD, multifocal lesions were significantly associated with the primary end point (HR, 7.1; 95% CI, 1.7-28.3), while LT was protective (HR, 0.3; 95% CI, 0.1-0.9). In PSC-UC patients with IND, 5-ASA use was associated with a decreased the risk of neoplasia progression, regardless of transplant status. In contrast, multifocal IND and LGD were associated with neoplasia progression or persistent LGD. Patients who developed LGD following LT for PSC were less likely to have progressive neoplasia or persistent LGD, compared with those who had not been transplanted.

Outcome Following Aminosalicylate Therapy in Children Newly Diagnosed As Having Ulcerative Colitis

Despite a paucity of published supporting data, 5-aminosalicylate (5-ASA) use in pediatric ulcerative colitis (UC) is common. The present study describes the use and outcome of a large multicenter inception cohort of children with UC treated with 5-ASA. Data were obtained from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry, a prospective North American observational study of children newly diagnosed as having inflammatory bowel disease ages 16 years or younger. Patient data are recorded at diagnosis, 30 days, and then quarterly. Patients are managed by physician dictate, not protocol. Disease activity is classified by physician global assessment. The primary outcome examined was corticosteroid (CS) free, inactive UC at 1 year following initiation of 5-ASA within 30 days of diagnosis (with or without concomitant CS use) without the need for rescue therapy (immunomodulators, biologics, or colectomy). Study subjects included 213 patients newly diagnosed as having UC who received oral 5-ASA compounds (115 of whom also received CS) during the first 30 days after diagnosis, and no other oral therapies for the treatment of UC. Of these 213 patients, 86 (40%) were CS free and physician global assessment inactive at 1 year without rescue. Outcome was not associated with disease severity at diagnosis, demographic or laboratory factors examined, or initial dose of 5-ASA used. Forty percent of children taking 5-ASA as primary maintenance therapy at diagnosis are in CS-free remission after 1 year of treatment. Further pediatric studies will be needed to address whether increased adherence and/or higher dosing schedules will improve outcomes.

Randomized Controlled Trials in Active Luminal Crohn’s Disease

Many trials focused on the treatment of active luminal Crohn's disease (CD) have been published in literature. A critical reevaluation of the main trials regarding the use of 5-ASA derivates has shown a not significant benefit of such molecules in treating CD and, as a consequence, the European Crohn's and Colitis Organization's (ECCO) therapeutic statements highlight that 5-ASA should be considered clinically no more effective than placebo for active disease. The main evidence regarding the efficacy of conventional steroids as inductive therapy in active CD is still based on the old but fundamental Cooperative studies which can be considered at low risk for biases in spite of the date of publication. Most probably these RCTs will remain unsurpassed. Current data do not support the use of antibiotics for active luminal CD as primary therapeutic strategy in view of very conflicting results. In accordance with these conclusions current guidelines dot not suggest this kind of treatment in active CD. Even if frequently used, data about the role of conventional immunosuppressors for the therapy of active luminal CD ara scanty. Azathioprine/6-MP should be no more considered as remission-inductive agents for active CD while methotrexate could be considered an effective therapeutic option in inducing remission in this setting particular setting. A number of clinical trials are available about the use of anti-TNF alpha agents (infliximab, adalimumab) in active luminal CD. Both drugs are surely effective in inducing remission even if safety and economic concerns should be better considered and investigated.

Predictors of Colorectal Neoplasia Outcomes in Indefinite and Low-Grade Dysplasia in Patients with Primary Sclerosing Cholangitis and Ulcerative Colitis: ACG IBD Research Award

Purpose: Patients (pts) with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at an increased risk for colorectal neoplasia. We sought to examine the natural history of low-grade dysplasia (LGD) and indefinite dysplasia (IND) in order to identify factors associated with neoplasia progression or persistence in pts with PSC-UC. Methods: We performed a retrospective review of pts with PSC and UC who were diagnosed with LGD or IND (index lesion confirmed after review by a pathologist). LGD was classified as unifocal or multifocal and flat or raised. Raised lesions in an area of colitis were considered adenoma-like dysplasia (ALD). Sporadic adenomas were excluded. Pts were excluded if they had a prior colectomy, colorectal neoplasia, or liver transplant (LT) or did not follow up beyond 60 days of their index lesion. Pts were censored at the time of colectomy, last colonoscopy or LT, whichever was earliest. The primary end-point was neoplasia progression, or persistent LGD. Covariates were included into the multivariate model if they had a p-value of ≤0.05 in the univariate analysis. Results: Sixty-three pts (IND n=47, LGD n=16) were followed for 176 pt-years. The primary endpoint was reached in 56% of pts with LGD [cancer n=1; persistent LGD (multifocal n=2; ALD n=6)] and in 28% with IND (cancer n=3; HGD n=3; multifocal LGD n=2; ALD LGD n=1; flat LGD n=4). Compared to those with IND, pts with LGD were older (57 years versus 42 years, p<0.01), and had a longer duration of UC (28 years versus 10 years, p=0.03) and PSC (9 years versus 6 years, p=0.05). Compared to LGD, IND lesions were more likely to be flat (98% versus 50%, p<0.01) and found in an area of colitis (100% versus 81% p<0.01). Univariate analysis revealed that LGD (compared to IND) was associated with the primary endpoint, HR 4.02 (1.61-9.71) p<0.01. Of those with multifocal LGD at baseline, univariate analysis showed an association with the primary endpoint, HR 5.08 (0.97-23.79) p=0.05. PSC duration was associated with the endpoint, HR 0.87 (0.74-0.99) p=0.05, in pts with LGD. However, neither was associated with the primary outcome in the multivariate analysis. Among pts with IND, 5-ASA use was associated with a reduced risk of neoplasia progression, HR 0.18 (0.04-0.70) p=0.01 on univariate analysis. A multivariate analysis for the IND group was not performed since 5-ASA use was the only significant association detected. Conclusion: Pts with PSC and UC who developed LGD were more likely to have progressive or persistent neoplasia than those who had IND. However, more than one-quarter of IND pts also developed more advanced lesions. 5-ASA use appeared to protect against neoplasia progression in pts with IND.

Colonoscopic Evidence of Active Ulcerative Colitis Leads to Medication Changes in the Majority of Patients

Purpose: To determine whether endoscopic assessment of UC is associated with medication changes, and to examine UC treatment trends over the past decade. Methods: All patients with endoscopically active UC who had a colonoscopy (Visit 2 or V2) with at least one clinic visit prior to (Visit 1 or V1) and two clinic visits after (Visit 3 and 4, or V3, V4) were included. Disease activity was defined using Mayo UC subscores as mild (1), moderate (2) or severe (3) UC. Medications analyzed were 6-MP/Azathioprine, oral 5-Aminosalicylic acid (5-ASA), topical 5-ASA, sulfasalazine, oral steroids and topical steroids. The type and number of medications before and after colonoscopy were compared between mild and moderate/severe UC. Subset analysis of the types of medications prescribed over the duration of the study (1996-2008) was performed for different time intervals. Results: Ninety-one UC patients with 364 clinic visits had Mayo subscore of > 1 and were included in the analyses. 85% of these patients had a medication change during the 4 clinic visits over a median time frame of 18.6 months. Approximately one-third had a medication added following colonoscopy. Compared to mild UC (Mayo 1), patients with moderate to severe UC (Mayo 2 or 3) were more likely to have a medication added (V1 to V3 33.3% vs. 12.2%, p=0.02). The medication change was primarily in the use of AZA/6MP (47.6% vs. 14.3%, p=0.001) and a trend towards initiation of oral corticosteroids (16.7% vs. 4.1% p=0.07). Between 1996 and 2008, there was a three-fold increase in the use of 6MP/AZA in patients with endoscopically moderate to severe UC. The use of rectal steroids, sulfasalazine, and rectal 5-ASA all declined. Conclusion: Colonoscopic evidence of moderate to severe mucosal inflammation in UC (Mayo score of 2 or 3) is associated with significantly increased use of AZA/6MP. These findings are consistent with greater physician awareness of the importance of mucosal healing in UC patients and adjusting medications based on endoscopic disease activity. Further study is needed to determine whether these findings are replicated in a broad range of physician practice settings, and whether anti-TNF treatment parallels the increase usage of AZA/6MP.Table 1: Change in class of medication in relation to endoscopic findings ( N =91)

International variation in medication prescription rates among elderly patients with inflammatory bowel disease

Background and aimsThe elderly represent a growing demographic of patients with IBD. No study has previously described variations in care or medication prescriptions in senior patients with IBD. We compared prescription rates among elderly patients with IBD in four countries using health administrative data. MethodsDatabases from the United States (US), United Kingdom (UK), Denmark and Canada were queried. Variation in prescription rates between countries was assessed in patients ≥65y with prevalent IBD who had ≥1 prescription for an IBD-related medication in a given quarter between 2004 and 2009. Patients were identified using previously-reported, validated algorithms. Country-specific rates were compared in each quarter using Fisher's exact test. ResultsIn patients with Crohn's disease, Canada and US had higher prescription rates for oral 5-ASA (P<0.0001 in all quarters) and infliximab (P<0.05 in 22/24 quarters), while the US had higher rates of thiopurine usage (P<0.05 in 23/24 quarters). Canada had greater rates of methotrexate prescriptions (P<0.05 in 21/24 quarters analyzed). In patients with ulcerative colitis (UC), rates of oral steroid usage was lowest in the US (P<0.05 in 22/24 quarters) and oral 5-ASA use was highest in the US and Canada (P<0.0001 in all quarters). Canada and Denmark used more rectal therapy than the US. Infliximab usage in UC was significantly higher in the US and Canada after 2006. ConclusionsSignificant variation in medication prescription rates exists among countries. Future research should assess whether these differences were associated with disparities in outcomes and health care costs.

5-Aminosalicylic Acid Is Not Protective Against Colorectal Cancer in Inflammatory Bowel Disease: A Meta-Analysis of Non-Referral Populations

Some studies have demonstrated that 5-aminosalicylic acid (5-ASA) is associated with a reduced risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD). However, more recent population-based studies suggest no protective association. We conducted a systematic review that focused on non-referral studies to reassess the role of 5-ASA for this indication. We searched MEDLINE, EMBASE, and the Cochrane databases for studies of non-referral populations that assessed the association between 5-ASA use for at least 1 year and colorectal neoplasia between 1966 and 2011 and conducted a quantitative meta-analysis. Four observational studies fulfilled inclusion criteria. The pooled adjusted odds ratio (aOR) was 0.95 (95% confidence interval (CI): 0.66-1.38), but there was moderate heterogeneity (I2 = 58.2%; P = 0.07). A sensitivity analysis that included a fifth study in which 5-ASA use was only for a minimum of 3 months yielded a pooled aOR of 0.82 (95% CI: 0.54-1.26). A series of sensitivity analyses in which each of the four studies was excluded one at a time did not show any significant change in the overall pooled OR. We conducted a separate meta-analysis of nine clinic-based studies, which, in contrast, yielded a pooled OR of 0.58 (95% CI: 0.45-0.75). Our meta-analysis yielded inconsistent results that were dependent on the inclusion of either non-referral or clinic-based populations. Based on non-referral studies, there does not seem to be a protective effect of 5-ASA on CRC in IBD. However, heterogeneity among these studies limits their interpretation.

The Pharmacological Profile and Clinical Use of Mesalazine (5-Aminosalicylic Acid)

For more than 30 years mesalazine (5-aminosalicylic acid; 5-ASA) has been used for the treatment of chronic inflammatory bowel disease (IBD) especially in ulcerative colitis (UC). During this time various rectal and oral formulations have been developed. The modified drug delivery systems were designed to release sufficient 5-ASA at the sites of inflammation. Such a drug targeting strategy is needed for its topical action and especially because local concentrations in the mucosa will determine the clinical outcome. The absorbed part (20-40% of the dose) of 5-ASA is rapidly and presystemically acetylated (t1/2: 1-2.5 h; CL: 300-690 mL/min). Consequently, the systemic exposure of 5-ASA is low and adverse effects are in the range of placebo treatment. The polypotent 5-ASA has a wide spectrum of pharmacological properties and its exact mode of action is not yet clear. Recent meta-analyses of randomized placebo-controlled clinical trials provide convincing data that 5-ASA is the preferred first-line therapy for the acute treatment of mild-to-moderate UC (NNT:6) and for remission management (NNT:4). There is also some clinical benefit for patients with active Crohn's disease (NNT:7) and in the prevention of postsurgical relapse (NNT:10). There is increasing evidence that 5-ASA also has some therapeutic potential for chemoprevention of colorectal cancer, diverticular disease and irritable bowel syndrome. In all clinical studies, the side effects of 5-ASA were very low (5-10%), mild and comparable to placebo. Thus, its use is very safe and 5-ASA will remain an interesting and valuable agent. It is anticipated that more selective drug targeting, including galenic innovations and an optimized dosaging schedule, could result in some improvement of the wide use of 5-ASA.

The influence of 5-aminosalicylic acid on the progression of colorectal adenomas via the ss-catenin signaling pathway

Surveillance colonoscopy is an important strategy for prevention of colorectal cancer. 5-aminosalicylate (ASA) (mesalazine) is discussed as a chemopreventive agent as it reduces the cancer risk in ulcerative colitis patients. The current study analyses the effect of 5-ASA on Wnt/β-catenin signaling in vitro and in vivo in colon epithelial cells. The effect of 5-ASA was determined using a β-catenin/T-cell factor (TCF)-reporter assay and by western blotting in cultured colon cancer cells. Formalin fixed paraffin embedded material from 227 polyps removed from a subgroup of 56 patients, who participated in a randomized placebo-controlled 3-year prevention trial with 5-ASA was evaluated according to histomorphological characteristics and expression of β-catenin and target genes Cox2, cyclin D1 and E-cadherin as well as ornithine decarboxylase (ODC). Patients were grouped into a low-risk and a high-risk group according to the number of adenomas at initial colonoscopy. ß-catenin/TCF signaling activity was significantly reduced by 5-ASA treatment possibly through a reduction in ß-catenin levels. Moreover, 5-ASA significantly reduced ß-catenin levels and nuclear localization in patients' adenomas. In addition, 5-ASA also significantly changed expression of the downstream targets Cox2, cyclin D1 and E-cadherin, correlating with ß-catenin status. Moreover, 5-ASA significantly reduced levels of ODC in vivo. Expression of p53 was unaltered by the 5-ASA treatment. Our study shows a significant in vitro and long-term in vivo effect of 5-ASA on ß-catenin signaling as a key signaling pathway in the development of colorectal adenoma. Therefore, we suggest the use of 5-ASA as a promising drug for prevention of sporadic colorectal carcinoma.

Risk of Ulcerative Colitis-Associated Colorectal Cancer in China: A Multi-Center Retrospective Study

The number of patients with ulcerative colitis (UC) in China has increased in the past 10 years. Thus, it is anticipated that the incidence of UC-associated colorectal cancer (UC-CRC) will also increase. However, the risk of CRC in UC patients is still unknown in Chinese. The aim of this study was to identify the risk and risk factors of UC-CRC in Chinese. A total of 3,922 patients with UC were retrospectively collected from five central teaching hospitals in China, in which high-quality endoscopic and histological diagnoses were available from 1998 to 2009. The database of the UC and UC-associated CRC patients was evaluated. CRC was diagnosed 34 in patients, and the overall prevalence of CRC in patients with UC was 0.87%. The cumulative risk of developing CRC after a disease duration of 10 years was 1.15% (95% confidence interval [CI] 0.71-1.84%); 20 years, 3.56% (95% CI 2.14-5.89%); and 30 years, 14.36% (95% CI 7.57-26.3%). Longer disease duration, extensive colitis, and dysplasia found in the biopsy specimen were identified as risk factors for developing CRC. 5-ASA use was identified as a protective factor of UC-CRC. The period prevalence of CRC was lower than that reported from the West. However, the cumulative risk was found to be comparable to that of Western countries, which suggests that the period prevalence of UC-CRC in China may be growing in the future.

Is 5-ASA Still the Treatment of Choice for Ulcerative Colitis?

5-Amino-salacylic acid (5-ASA) is up to now the treatment of choice in the induction and maintenance of remission of mild-to-moderate ulcerative colitis (UC). Sulfasalazine, despite similar efficacy, is hampered by more side effects, but in presence of peripheral arthopaties it remains the treatment of choice. The new delayed release MMX formulation seems to be promising in reducing compliance problems, but further studies are warranted to show the superiority of new MMX formulation compared with the older formulations of 5-ASA. Some trials evaluated also the efficacy and safety of once-daily dosing of older 5-ASA formulations in maintenance of remission, finding a greater adherence to therapy in the group given the once daily regimen, compared with the classic twice daily groups. Regarding the efficacy of alternative treatment such us probiotics and antibiotics, the current data are not sufficient to promote their use in clinical practice. Clinical evidence supports the use of topical 5-ASA in active mild to moderate distal UC showing superior efficacy to placebo, topical corticosteroids, and oral 5-ASA. A combination of oral and rectal 5-ASA produces additional efficacy in both limited and extensive UC. Topical 5-ASA formulations are effective also for the maintenance of remission, however long term treatment may not be acceptable to many patients. Other topical drugs (E. Coli Nissle, propionyl-L-carnitine, butyrate, tacrolimus, rosiglitazone) have been investigated with conflicting results. The possible chemopreventive role of long term treatment with 5-ASA strengthens the indication to the long term use of 5-ASA.

Thiopurines prevent advanced colorectal neoplasia in patients with inflammatory bowel disease

Background and aimsPrevious studies have suggested a chemopreventive effect of 5-aminosalicylic acid (5-ASA) therapy in patients with inflammatory bowel disease (IBD). This effect has not been reported in IBD patients...

Optimizing clinical use of mesalazine (5-aminosalicylic acid) in inflammatory bowel disease

Mesalazine [5-aminosalicylic acid (5-ASA)] has been used for over 30 years in the treatment of inflammatory bowel disease (IBD). It is a highly effective, safe, and well-tolerated drug for treatment of mild to moderate ulcerative colitis, which represents most patients with this disease. Recent studies of patient adherence to 5-ASA therapies in ulcerative colitis have highlighted the need for regimens that enable long-term compliance to significantly reduce the risk of troublesome and debilitating flares in the short term, and possibly colon cancer in the long term. Indeed, much of the recent innovation in clinical use of 5-ASA in colitis has come from studies of novel delivery mechanisms and simplified oral dosing schedules. These studies have provided much needed clarity on essential matters such as starting dose, dose escalation, and efficacy in terms of the ideal clinical endpoint - mucosal healing. Various manufacturers are re-evaluating their products to determine the safety and efficacy of such dosing regimens. Although once widely employed in the treatment of Crohn's disease (CD), the accumulated body of evidence now suggests that there is a much more limited role for 5-ASA in this particular form of inflammatory bowel disease. Recent 5-ASA randomized-controlled trials, comparative studies, and outcomes research have led to refined treatment strategies and awareness for practitioners to better inform, engage and facilitate patients in optimal use of 5-ASA in inflammatory bowel disease.