Aminosalicylates target GPR35, partly contributing to the prevention of DSS-induced colitis.

GPR35, a class A G-protein-coupled receptor, is considered an orphan receptor; the endogenous ligand and precise physiological function of GPR35 remain obscure. GPR35 is expressed relatively highly in the gastrointestinal tract and immune cells. It plays a role in colorectal diseases like inflammatory bowel diseases (IBDs) and colon cancer. More recently, the development of GPR35 targeting anti-IBD drugs is in solid request. Nevertheless, the development process is in stagnation due to the lack of a highly potent GPR35 agonist that is also active comparably in both human and mouse orthologs. Therefore, we proposed to find compounds for GPR35 agonist development, especially for the human ortholog of GPR35. As an efficient way to pick up a safe and effective GPR35 targeting anti-IBD drug, we screened Food and Drug Administration (FDA)-approved 1850 drugs using a two-step DMR assay. Interestingly, we found aminosalicylates, first-line medicine for IBDs whose precise target remains unknown, exhibited activity on both human and mouse GPR35. Among these, pro-drug olsalazine showed the most potency on GPR35 agonism, inducing ERK phosphorylation and ß-arrestin2 translocation. In dextran sodium sulfate (DSS)-induced colitis, the protective effect on disease progression and inhibitory effect on TNFα mRNA expression, NF-κB and JAK-STAT3 pathway of olsalazine are compromised in GPR35 knock-out mice. The present study identified a target for first-line medicine aminosalicylates, highlighted that uncleaved pro-drug olsalazine is effective, and provided a new concept for the design of aminosalicylic GPR35 targeting anti-IBD drug.

Risk of postoperative infectious complications from medical therapies in inflammatory bowel disease.

BACKGROUND: Medications used to treat inflammatory bowel disease (IBD) have significantly improved patient outcomes and delayed time to surgery. However, some of these therapies are recognized to increase the general risk of infection and have an unclear impact on postoperative infection risk. OBJECTIVES: To assess the impact of perioperative IBD medications on the risk of postoperative infections within 30 days of surgery. SEARCH METHODS: We searched the Cochrane IBD Group's Specialized Register (29 October 2019), MEDLINE (January 1966 to October 2019), Embase (January 1985 to October 2019), the Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform from inception up to October 2019, and reference lists of articles. SELECTION CRITERIA: Randomized controlled trials, quasi-randomized controlled trials, non-randomized controlled trials, prospective cohort studies, retrospective cohort studies, case-control studies and cross-sectional studies comparing participants treated with an IBD medication preoperatively or within 30 days postoperatively to those who were not taking that medication (either another active medication, placebo, or no treatment). We included published study reports and abstracts. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts and extracted data. The primary outcome was postoperative infection within 30 days of surgery. Secondary outcomes included incisional infections and wound dehiscence, intra-abdominal infectious complications and extra-abdominal infections. Three review authors assessed risks of bias using the Newcastle-Ottawa Scale. We contacted authors for additional information when data were missing. For the primary and secondary outcomes, we calculated odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) using the generic inverse variance method. When applicable, we analyzed adjusted and unadjusted data separately. We evaluated the certainty of the evidence using GRADE. MAIN RESULTS: We included 68 observational cohort studies (total number of participants unknown because some studies did not report the number of participants). Of these, 48 studies reported including participants with Crohn's disease, 36 reported including participants with ulcerative colitis and five reported including participants with indeterminate colitis. All 42 studies that reported urgency of surgery included elective surgeries, with 31 (74%) of those also including emergency surgeries. Twenty-four studies had low risk of bias while the rest had very high risk. Based on pooling of adjusted data, we calculated ORs for postoperative total infection rates in participants who received corticosteroids (OR 1.70, 95% CI 1.38 to 2.09; low-certainty evidence), immunomodulators (OR 1.29, 95% CI 0.95 to 1.76; low-certainty evidence), anti-TNF agents (OR 1.60, 95% CI 1.20 to 2.13; very low-certainty evidence) and anti-integrin agents (OR 1.04, 95% CI 0.79 to 1.36; low-certainty evidence). We pooled unadjusted data to assess postoperative total infection rates for the use of aminosalicylates (5-ASA) (OR 0.76, 95% CI 0.51 to 1.14; very low-certainty evidence). One secondary outcome examined was wound-related complications in participants using: corticosteroids (OR 1.41, 95% CI 0.72 to 2.74; very low-certainty evidence), immunomodulators (OR 1.35, 95% CI 0.96 to 1.89; very low-certainty evidence), anti-TNF agents (OR 1.18, 95% CI 0.83 to 1.68; very low-certainty evidence) and anti-integrin agents (OR 1.64, 95% CI 0.77 to 3.50; very low-certainty evidence) compared to controls. Another secondary outcome examined the odds of postoperative intra-abdominal infections in participants using: corticosteroids (OR 1.53, 95% CI 1.28 to 1.84; very low-certainty evidence), 5-ASA (OR 0.77, 95% CI 0.45 to 1.33; very low-certainty evidence), immunomodulators (OR 0.86, 95% CI 0.66 to 1.12; very low-certainty evidence), anti-TNF agents (OR 1.38, 95% CI 1.04 to 1.82; very low-certainty evidence) and anti-integrin agents (OR 0.40, 95% CI 0.14 to 1.20; very low-certainty evidence) compared to controls. Lastly we checked the odds for extra-abdominal infections in participants using: corticosteroids (OR 1.23, 95% CI 0.97 to 1.55; very low-certainty evidence), immunomodulators (OR 1.17, 95% CI 0.80 to 1.71; very low-certainty evidence), anti-TNF agents (OR 1.34, 95% CI 0.96 to 1.87; very low-certainty evidence) and anti-integrin agents (OR 1.15, 95% CI 0.43 to 3.08; very low-certainty evidence) compared to controls. AUTHORS' CONCLUSIONS: The evidence for corticosteroids, 5-ASA, immunomodulators, anti-TNF medications and anti-integrin medications was of low or very low certainty. The impact of these medications on postoperative infectious complications is uncertain and we can draw no firm conclusions about their safety in the perioperative period. Decisions on preoperative IBD medications should be tailored to each person's unique circumstances. Future studies should focus on controlling for potential confounding factors to generate higher-quality evidence.

Pharmacokinetics of Para-Aminosalicylic Acid and Its 2 Major Metabolites: A Potential Relationship to the Development of Gastrointestinal Intolerance.

Para-aminosalicylic acid (PAS), often the last drug remaining for treatment of drug-resistant tuberculosis, is notorious for causing gastrointestinal intolerance; however, the cause of PAS intolerance is uncertain. The objective of this study was to assess relationships between peak concentrations of PAS administered as a granular slow-release enteric coated formulation, and its metabolites acetyl-PAS and glycine-PAS, and intolerance. PAS and its metabolites were measured in 29 adult patients with drug-resistant tuberculosis at Brooklyn Hospital, Cape Town, randomized to receive granular slow-release enteric-coated PAS 4 g twice daily or 8 g once daily for 1 week, followed by the alternative regimen. Concentrations of PAS and its metabolites were determined by liquid chromatography and tandem mass spectrometry, and a visual analogue scale evaluated intolerance. Spearman's correlation test assessed the relationship between maximum plasma concentrations (Cmax ) and intolerance scores. A large interindividual variability was observed for the PAS Cmax (40.42-68.55 mg/L) following 4 g twice daily; (62.69-102.41 mg/L) for 8 g once daily and a similar wide Cmax range found for the metabolites acetyl-PAS and glycine-PAS. Twenty-six patients reported at least 1 intolerance episode, but most visual analogue scale scores clustered around 0. Significant inverse associations were found between acetyl-PAS Cmax and bloating (rho = -0.448; P = .025) and diarrhea (rho = -0.407; P = .044) for the twice-daily regimen and a similar inverse association found for glycine-PAS and diarrhea (rho = -0.412; P = .041). Plasma concentrations of the metabolites did not correlate with the occurrence of gastrointestinal symptoms, but higher metabolite concentrations correlated with lower intolerance scores; slow metabolism of PAS and its continued presence in the intestinal tract may be the main cause of intolerance.

5-aminosalicylic acid agents for prevention of recurrent diverticulitis: A systematic review and meta-analysis.

BACKGROUND AND AIM: Prevalence of colonic diverticulosis is increasing worldwide with age, and up to 25% of patients who have colonic diverticulosis might experience diverticulitis. However, a definitive approach of preventing recurrent diverticulitis remains unknown. 5-aminosalicylic acid (5-ASA) agents are anti-inflammatory agents and have been used to prevent recurrent diverticulitis, and there have been some randomized clinical trials (RCTs). However, the efficacy results for secondary prevention in uncomplicated diverticulitis differed across studies. Our aim was to clarify the efficacy and safety of 5-ASA agents in the prevention of recurrent diverticulitis. METHODS: We searched MEDLINE, EMBASE, Web of Science, and the Cochrane library with no language restrictions. Two reviewers independently assessed and selected RCTs. The data were pooled using a random effect model and were presented in the pooled risk ratio (RR) and 95% confidence interval (CI). Cochrane's Q and I-squared statistics were used to assess heterogeneity. The protocol was registered at PROSPERO. RESULTS: Seven articles with eight RCTs from 329 potentially relevant articles were included. 5-ASA agents were not superior to controls in preventing recurrent diverticulitis (RR 0.86, 95% CI 0.63 to 1.17, I2  = 60%) and the incidence of adverse events was not different between 5-ASA agents and controls (RR 0.97, 95% CI 0.84 to 1.11, I2  = 45%). However, some included studies were few in number of participants and substantial risk of bias. CONCLUSIONS: 5-aminosalicylic acid agents were not associated with prevention of recurrent diverticulitis.

The safety of non-biological treatments in Ulcerative Colitis.

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a relapsing-remitting course that determines significant morbidity and can associate with local complications and/or extra-intestinal manifestations. Pharmacological therapies are often required for a lifetime with possible risks of toxicity and side effects. Areas covered: Non-biological therapies (i.e. aminosalicylates, corticosteroids and immunosuppressive drugs) are widely used in UC patients for controlling the active phases of the disease and maintaining remission. Expert Opinion: Aminosalycilates have a good safety profile with a low risk of idiosyncrasic reactions. In contrast, the use of corticosteroids and immunosuppressive drugs can associate with unacceptable side effects, some of which are potentially life threatening. Mechanisms underlying the development of these side effects are not fully understood and strategies aimed to prevent them have not yet been standardized. However, clinicians should monitor the patients during therapy to recognize the adverse events at an early stage of the occurrence. New drugs that selectively target molecules involved in the amplification of the ongoing mucosal inflammation are currently under investigation. Preliminary data indicate that such compounds have better overall safety and tolerability than corticosteroids and immunosuppressive drugs.

Medication-Induced Interstitial Nephritis in the 21st Century.

Interstitial nephritis is an immune mediated form of tubulointerstitial kidney injury that may occur secondary to drugs, autoimmune disease, infections, and hematologic disorders or as a reactive process. Drug-induced acute interstitial nephritis (DI-AIN) occurs in 0.5%-3% of all kidney biopsies and in 5%-27% of biopsies performed for acute kidney injury. Drugs are implicated in 70%-90% of biopsy-proved IN with a prevalence of 50% in less developed to 78% in more developed countries. DI-AIN typically is idiosyncratic because of a delayed hypersensitivity reaction, although some chemotherapeutic agents are permissive for immune upregulation and injure the kidney in a dose-related manner. Antibiotics are the most implicated class of medication in DI-AIN, followed by proton pump inhibitors, nonsteroidal anti-inflammatory agents, and 5-aminosalicylates. Diuretics, allopurinol, phenytoin and other anti-seizure medications, and H2 receptor antagonists are known offenders while chemotherapeutic agents are an under-recognized cause. The symptoms of DI-AIN are variable and often not specific; thus, kidney biopsy is required to make a firm diagnosis. The incidence of DI-AIN appears to be increasing, particularly in the elderly in whom kidney biopsy is underused, and identification of the offending agent may be complicated by polypharmacy. As rapid drug discontinuation may improve prognosis, the possibility of DI-AIN should always be considered in a patient with acute kidney injury.

The safety of treatment options for pediatric Crohn's disease.

INTRODUCTION: A severe clinical phenotype along with concern for ensuring normal growth and development has a major impact on treatment choices for children newly diagnosed with Crohn's disease (CD). AREAS COVERED: We review the increasingly outdated concept of 'conventional' therapy of pediatric CD based on aminosalicylates, corticosteroids, and immunomodulators for patients at high risk of complicated disease. Key safety concerns with each treatment are reviewed. EXPERT OPINION: There are minimal data supporting the use of aminosalicylates in the treatment of pediatric CD. Corticosteroids are effective short-term for improving signs and symptoms of disease but are ineffective for maintenance therapy. Thiopurines decrease corticosteroid dependence but may not alter progression to complicated disease requiring surgery. Concerns for lymphoma as well as hemophagocytic lymphohistiocytosis with thiopurines are valid. Further data are required on the efficacy and safety of methotrexate as an alternative immunomodulator. Though generally well tolerated and efficacious in most patients, anti-TNF-α therapy can be associated with both mild as well as more serious complications. Current data do not support an increased risk for malignancy associated with anti-TNF therapy alone in children. Anti-adhesion therapy appears to have a favorable safety profile but the experience in children is extremely limited.

The use of biologic therapy in pregnancy: a gastroenterologist's perspective.

PURPOSE OF REVIEW: Inflammatory bowel disease (IBD) often affects women in their peak reproductive years, and therapy is often continued during pregnancy to maintain stable disease activity. Therapeutic options have expanded over the last 2 decades with the advent of new biologic options. It is, therefore, important for the gastroenterologists and other clinicians caring for patients with IBD to understand safety data regarding the treatment options, both biologic and nonbiologic, in pregnant IBD patients. RECENT FINDINGS: In general, quality of evidence in this area remains low. However, larger prospective studies are beginning to provide evidence regarding the potential safety of biologics both alone and in conjunction with nonbiologic therapy. SUMMARY: The majority of treatment options for IBD appears to be of low risk and may often be continued through pregnancy and lactation. Not treating IBD, for example, by discontinuing therapy prior to or with pregnancy, may pose a greater risk to mother and fetus in many cases.

Thrombocytopenia associated with 5-aminosalicylate prodrug, olsalazine: is the devil still there?

CASE DESCRIPTION: We present a case of a 63-year-old Chinese female who developed severe thrombocytopenia after receiving olsalazine 1.5 g daily for 3 months, and eventually culminated in hospital admission. According to a Medline search, this is the first case report of olsalazine-associated thrombocytopenia in Asia. CONCLUSION: Olsalazine, similar to other 5-aminosalicylates, can also cause thrombocytopenia. Clinicians should be aware of this potential adverse drug reaction. Future studies should focus on the trigger mechanism and possible cross-reaction between olsalazine and other aminosalicylates.

Colorectal neoplasia in patients with primary sclerosing cholangitis undergoing liver transplantation: a Nordic multicenter study.

OBJECTIVE: Several studies have implicated primary sclerosing cholangitis (PSC) as an additional risk factor for colorectal neoplasia in inflammatory bowel disease (IBD). Some reports have indicated that the risk is even higher in PSC-IBD patients after liver transplantation (Ltx), but this issue is controversial. We aimed to compare the risk of colorectal neoplasia in PSC-IBD patients before and after Ltx and to identify risk factors for colorectal neoplasia post-transplant. MATERIAL AND METHODS: In a multicenter study within the Nordic Liver Transplant Group, we assessed the risk of colorectal neoplasia by using the competing risk regression analysis. RESULTS: Among the 439 PSC patients included, 353 (80%) had IBD at the time of Ltx and 15 (3%) patients developed de novo IBD post-Ltx. The median duration of IBD was 15 (0-50) years at the time of Ltx and follow-up after Ltx was 5 (0-20) years. Ninety-one (25%) PSC-IBD patients developed colorectal neoplasia. The cumulative risk of colorectal neoplasia was higher after than before Ltx (HR: 1.9, 95% CI: 1.3-2.9, p = 0.002). A multivariate analysis demonstrated aminosalicylates and ursodeoxycholic acid as significantly associated with an increased risk of colorectal neoplasia post-Ltx. Duration and activity of IBD did not significantly affect the risk of neoplasia. CONCLUSION: The even higher risk of colorectal neoplasia in PSC-IBD patients after when compared with that of before Ltx underscores the importance of regular surveillance colonoscopies post-Ltx. The association of aminosalicylates and ursodeoxycholic acid to the development of colorectal neoplasia after Ltx should be further investigated.

Drug-induced nephrotoxicity in inflammatory bowel disease.

Conservative management of inflammatory bowel disease (IBD) is based on a combination of drugs, including aminosalicylates (ASAs), steroids, antibiotics, immunosuppressives and biologic agents. Although various side effects have been related to treatment regimens, drug-induced nephrotoxicity is rather uncommon. Furthermore, it is often underestimated since renal function deterioration may be attributed to the underlying disease. The nephrotoxicity of ASAs and cyclosporine A seems well established, but recent data have suggested a possible role of biologic agents such as infliximab and adalimubab in renal impairment. The aim of this review is to summarize the nephrotoxic effects of medical treatment as well as to express possible caveats in the administration of novel agents in IBD.

[Mesalazine old and new]. / Mesalazinas viejas, mesalazinas nuevas.

Aminosalycylates (5-ASA) are still the drugs of choice both for mild-to-moderate outbreaks of ulcerative colitis and to maintain long-term remission. The efficacy of these drugs has been widely demonstrated in placebo-controlled trials. However, when administered orally, their pharmacological characteristics hamper the desired therapeutic effect. Currently, efficiency can be optimized by exclusive or combined rectal administration. The present article reviews the available data on the efficacy of galenic preparations of 5-ASA and discusses the potential advantages of galenic forms of 5-ASA coated with a novel multi-matrix delivery system.

High thiopurine metabolite concentrations associated with lymphopenia in inflammatory bowel disease (IBD) pediatric patients receiving aminosalicylates combined with azathioprine.

OBJECTIVE: Aminosalicylates are widely used with azathioprine in the treatment of IBD. The association results in an increase in 6-TGN levels in adults with IBD with a difference in the occurrence of myelotoxic effects. Scarce data are available in pediatric population. We proposed to investigate the effect of the coadministration of aminosalicylates on thiopurine concentrations in pediatric IBD patients. MATERIALS AND METHODS: Data from 71 patients treated for at least 1 y by azathioprine and aminosalicylates were recorded. 6-TGN and 6-MeMPN concentrations, blood cell counts and liver function tests were compared between patients taking and those not taking aminosalicylates. RESULTS: Aminosalicylate therapy was associated with a significant increase in mean 6-TGN but also 6-MeMPN concentrations. In patients in remission, 6-TGN level was related to aminosalicylate dosage (r = 0.561, p = 0.010). Lymphopenia rate was higher in patients receiving combined therapy compared to monotherapy whereas a slight rise in leucopenia was found. CONCLUSIONS: This observation suggests that the higher frequency of lymphopenia may be associated with the elevated 6-TGN concentrations recovered in patients treated with aminosalicylates. This combination does not improve remission rate but could increase adverse effects especially lymphopenia.

Safety, efficacy, and pharmacokinetics of balsalazide in pediatric patients with mild-to-moderate active ulcerative colitis: results of a randomized, double-blind study.

OBJECTIVES: : A multicenter, double-blind study was conducted to evaluate the safety, efficacy, and pharmacokinetics of balsalazide in pediatric patients with mild-to-moderate ulcerative colitis (UC). PATIENTS AND METHODS: : Sixty-eight patients, 5 to 17 years of age, with mild-to-moderate active UC based on the modified Sutherland UC activity index (MUCAI) were randomized to receive oral balsalazide 2.25 or 6.75 g/day for 8 weeks. The primary endpoint was clinical improvement (reduction of the MUCAI score by > or =3 points from baseline). Clinical remission (MUCAI score of 0 or 1 for stool frequency) and histological improvement after 8 weeks were also assessed. Pharmacokinetic parameters for balsalazide, 5-aminosalicylic acid, and N-acetyl-5-aminosalicylic acid were determined at 2 weeks. Adverse events and laboratory changes were monitored throughout the study. RESULTS: : Clinical improvement was achieved by 45% and 37% of patients and clinical remission by 12% and 9% of patients receiving 6.75 and 2.25 g/day, respectively. Improvement in histologic grade was achieved by 8 of 16 (50%) and 3 of 10 (30%) patients receiving 6.75 and 2.25 g/day, respectively. No significant differences were seen in efficacy. Pharmacokinetics in 12 patients were characterized by large interpatient variability and low systemic exposure. Adverse events were similar between the treatment groups, the most common being headache and abdominal pain. No clinically significant changes were observed in laboratory values, including those indicative of hepatic or renal toxicity. CONCLUSIONS: : Balsalazide is well tolerated and improves the signs and symptoms of mild-to-moderate active UC in pediatric patients 5 to 17 years of age.

A meta-analysis of the efficacy of sulfasalazine in comparison with 5-aminosalicylates in the induction of improvement and maintenance of remission in patients with ulcerative colitis.

BACKGROUND: Historically, sulfasalazine (SSZ) and 5-aminosalicylates (5-ASAs) have been a mainstay of mild-to-moderate ulcerative colitis (UC) remission induction and maintenance therapy. Considering the pivotal role of intestinal microbial flora in pathophysiology of UC and antimicrobial activity of sulfapyridine, we hypothesized that SSZ might be more effective than 5-ASAs in the management of UC. AIM: To compare the efficacy and tolerability of SSZ with each of the 5-ASAs (mesalamine, olsalazine, and balsalazide) by a meta-analysis technique. METHODS: Pubmed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies compared efficacy and/or tolerability of SSZ with 5-ASAs in the management of UC. The search terms were: "sulfasalazine" or "sulfasalazine" and "5-aminosalicylic acid," "mesalazine," "mesalamine," "olsalazine" or "balsalazide" and "ulcerative colitis." Data were collected from 1966 to April 2008. There was no language restriction. "Overall improvement," "relapse rate," "total adverse events," and "withdrawals because of adverse events" were the key outcomes of interest. RESULTS: Twenty randomized placebo controlled trials met our criteria and were included in the meta-analysis. Comparison of SSZ with mesalamine yielded a nonsignificant relative risk (RR) of 1.04 (95% confidence interval of 0.89-1.21, P = 0.63) for overall improvement, a nonsignificant RR of 0.98 (95% CI 0.78-1.23, P = 0.85) for relapse, a nonsignificant RR of 0.76 (95% CI 0.54-1.07, P = 0.11) for any adverse events, and a nonsignificant RR of 0.78 (95% CI 0.46-1.3, P = 0.33) for withdrawals due to adverse events. Comparison of SSZ with olsalazine yielded a nonsignificant RR of 1.14 (95% CI 0.91-1.43, P = 0.25) for overall improvement, a nonsignificant RR of 0.93 (95% CI 0.77-1.12, P = 0.42) for relapse, a nonsignificant RR of 1.21 (95% CI 0.9-1.61, P = 0.20) for any adverse events, and a nonsignificant RR of 1.53 (95% CI 0.93-2.52, P = 0.09) for withdrawals due to adverse events. Comparison of SSZ with balsalazide yielded a nonsignificant RR of 1.3 (95% CI 0.93-1.81, P = 0.12) for overall improvement, and a significant RR of 0.17 (95% CI 0.06-0.49, P = 0.001) for withdrawals because of adverse events. CONCLUSION: SSZ does not differ from mesalamine or olsalazine in terms of efficacy and tolerability in UC. Withdrawal from study due to adverse events was significantly lower for balsalazide compared with SSZ. Convincing conclusions on the comparison of effectiveness and safety of balsalazide and SSZ in UC remains to be elucidated by further clinical trials. Considering the lower cost of treatment with SSZ and the equal rate of adverse events with other 5-ASAa, it is not surprising to suggest SSZ as a first-choice treatment for UC and reserve 5-ASAs for when SSZ intolerability occurs.

Novel 5-aminosalicylic acid formulations in ulcerative colitis: old dog, new tricks.

Ulcerative colitis is a chronic inflammatory bowel disease, often associated with abdominal pain, rectal bleeding, fatigue, and poor quality of life. Although 5-aminosalicylic acid (5-ASA) preparations are the mainstay of treatment of this condition, the observed efficacy of many current formulations is limited by delivery systems that require multiple-daily dosing schedules and are associated with poor patient adherence. It is of critical importance that patients adhere to medication regimens, because failure to do so has been shown to result in a greater number of disease flares and an increased risk of complications, including colorectal cancer. Patient-friendly formulations of 5-ASA have recently been approved or are in development to overcome the limitations of many older formulations and improve remission rates. As a major point of contact for many patients with ulcerative colitis, it is essential that gastrointestinal nurses keep abreast of such relevant developments in treatment options. Indeed, nurses are a crucial educational conduit for patients and are in a unique position to serve as trusted educators on important issues. This review provides an update on recent advances in 5-ASA therapy to ensure that gastrointestinal nurses are aware of potential strategies for improving clinical outcomes of patients with ulcerative colitis.

Effects and treatment of inflammatory bowel disease during pregnancy.

QUESTION: I have several patients with inflammatory bowel disease (IBD) who are pregnant or planning pregnancies. What information can I give them regarding the possible effects of IBD on pregnancy and the medications used to treat IBD during pregnancy? ANSWER: Women with IBD appear to be at increased risk of giving birth prematurely, having low-birth-weight infants, and having cesarean sections. Neither 5-aminosalicylic acid nor sulfasalazine has been found to increase the rate of major malformations, fetal mortality, or morbidity. There is conflicting evidence regarding the use of corticosteroids and azathioprine and 6-mercaptopurine. There are limited data on the use of infliximab during pregnancy, although no pattern of defects or complications has been reported to date.

Ulcerative colitis: responding to the challenges.

Aminosalicylates are the first-line therapy for patients with mild to moderate active ulcerative colitis. Treatment should start at dosages of 4.8 g per day of the active 5-aminosalicylate moiety, rather than starting at a lower dosage and increasing if treatment fails. Infliximab has been shown to be effective and is now approved by the US Food and Drug Administration for the treatment of moderately to severely active ulcerative colitis in patients who have had an inadequate response to conventional therapy.