5-ASA Derivatives Research Articles

Enhancing Oral 5-ASA Effectiveness in Mild-to-Moderate Ulcerative Colitis through an H. erinaceus-Based Nutraceutical Add-on Multi-Compound: The "HERICIUM-UC" Two-Arm Multicentre Retrospective Study.

Mild-to-moderate ulcerative colitis (UC) management is centred on 5-aminosalicylic acid (5-ASA) derivatives. Whether supplementing 5-ASA with nutraceuticals can provide real advantages in UC-relevant outcomes is unclear. This retrospective multicentre study compared clinical remission, response rates, and faecal calprotectin levels in a two-arm design, including patients treated with 5-ASA alone and those with additional H. erinaceus-based multi-compound supplementation. In the 5-ASA alone group, clinical response rates were 41% at three months (T1) and 60.2% at six months (T2), while corresponding clinical remission rates were 16.9% and 36.1%. In the nutraceutical supplementation group, clinical response rates were 49.6% (T1) and 70.4% (T2), with clinical remission rates of 30.4% (T1) and 50.9% (T2). No significant differences in clinical response rates between the groups at T1 (p = 0.231) and T2 (p = 0.143) emerged. Clinical remission rates differed significantly at both time points (p = 0.029 and p = 0.042, respectively). Faecal calprotectin levels decreased significantly in both groups during the retrospective follow-up (p < 0.05), and this was more pronounced in nutraceutical supplementation patients at both T1 (p = 0.005) and T2 (p = 0.01). No adverse events were reported. This multi-component nutraceutical supplementation offers real-world potential in controlling disease activity in patients with mild-to-moderate UC.

Inflammatory bowel disease in the elderly: A focus on disease characteristics and treatment patterns.

As the population ages, the number of elderly inflammatory bowel disease (IBD) patients is expected to increase. The clinical features and therapeutic options for young and old patients may differ, as elderly IBD patients are likely to have different comorbidities and disease characteristics. The goal of this study was to examine the clinical aspects and therapeutic choices for elderly Saudi IBD patients. We conducted a retrospective study aimed at describing the demographic, clinical, and management characteristics of IBD in elderly patients (≥60 years) who followed up at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. The data was extracted from the KAUH inflammatory bowel disease information system (IBDIS) registry. The primary outcome was to describe disease characteristics in accordance with the Montréal classification and the secondary outcomes were to describe treatment patterns and identify significant clinical associations. Our data were collected from 76 patients who fulfilled the study inclusion criteria. Females outnumbered males (53.9% vs 46.1%) and the mean age was 51.5 ± 9.7 years. Essential hypertension (26.3%) was the most common comorbidity followed by diabetes mellitus (23.6%), and malignant neoplasms (9.21%). More than half of the patients with Crohn's disease (CD) had disease onset after forty years of age. The most common form of disease distribution was ileocolonic disease (64.7%). Less than 17% of patients had a penetrating disease phenotype. About 88 percent of patients with UC presented >40 years of age. Approximately, half of the cohort had left-sided ulcerative colitis (UC) (48%), followed by pancolitis (40%). The most prescribed medication class for IBD was 5-aminosalicylic acid (5-ASA) derivatives (56.58%) followed by corticosteroids and immunosuppressive drugs. In Saudi Arabia, age-specific concerns including comorbidities and polypharmacy remain the major challenges in the management of elderly IBD patients.

S2779 A Drug After My Own Heart: Mesalamine-Induced Perimyocarditis

Introduction: Mesalamine is a commonly used first line treatment to induce remission in mild to moderate Ulcerative Colitis (UC) that many patients tolerate well. However it does not come without risk and can rarely cause serious and life threatening cardiac and lung inflammation including myocarditis. Case Description/Methods: A 33 year old male with recently diagnosed ulcerative pancolitis presented with one day of pleuritic, positional chest pain and exertional dyspnea. Two months prior to presentation he had been diagnosed with moderate pancolonic ulcerative colitis and started on mesalamine 1.2 gm twice daily and mesalamine 1000mg suppository every evening, with significant improvement in his symptoms. On presentation, laboratory evaluation was remarkable for elevated troponin to 0.918 and elevated brain naturetic peptide to 2770. Electrocardiogram showed diffuse PR depression and ST elevations consistent with pericarditis. The patient was admitted for further evaluation. Mesalamine was stopped and he was started on Ibuprofen and colchicine with improvement in his pain. Common viral etiologies were ruled out with polymerase testing. A transthoracic echocardiogram revealed moderate global hypokinesis with a reduced ejection fraction (EF) of 25%. A cardiac MRI showed hyperenhancement throughout basal-to-mid inferior and inferolateral wall with ∼5% scar burden proving the diagnosis of perimyocarditis. At 1 month follow up his EF recovered to 52%. His UC symptoms have returned since stopping therapy though he remains hesitant to start other UC therapy given concerns regarding adverse effects. (Figure) Discussion: Mesalamine induced myocarditis is a rare but potentially lethal complication. It typically occurs within 1-2 weeks of starting the medication but has been reported as early as 48 hours and as late as 4 weeks. The specific pathogenesis of Mesalamine induced myocarditis is unknown. Withdrawal of mesalamine leads to symptomatic improvement in most patients as well as recovery of ejection fraction within weeks of discontinuing the medication, as seen with our patient. Future treatment with mesalamine and other 5-ASA derivatives should be avoided as they can trigger recurrent symptoms. Our case highlights a rare and life threatening complication of a commonly used medication. It also highlights the importance of discussing the potential risks of medications with patients. While rare, these authors recommend discussing the potential for myocarditis when counseling patients on treatment options for UC.Figure 1.: Cardiac MRI with myocardial inflammation.

INFLAMMATORY BOWEL DISEASE CARE IN BRAZIL: HOW IT IS PERFORMED, OBSTACLES AND DEMANDS FROM THE PHYSICIANS' PERSPECTIVE.

Inflammatory bowel diseases (IBD) are chronic inflammatory affections of recurrent nature whose incidence and prevalence rates have increased, including in Brazil. In long term, they are responsible for structural damage that impacts quality of life, morbidity and mortality of patients. To describe the profile of physicians who treat IBD patients as well as the characteristics of IBD care, unmet demands and difficulties. A questionnaire containing 17 items was prepared and sent to 286 physicians from 101 Brazilian cities across 21 states and the Federal District, selected from the register of the State Commission of the "Study Group of Inflammatory Bowel Disease of Brazil" (GEDIIB). The majority of the physicians who answered the questionnaire were gastroenterologists and colorectal surgeons. More than 60% had up to 20 years of experience in the specialty and 53.14% worked at three or more locations. Difficulties in accessing or releasing medicines were evident in this questionnaire, as was referrals to allied healthy professionals working in IBD-related fields. More than 75% of physicians reported difficulties in performing double-balloon enteroscopy and capsule endoscopy, and 67.8% reported difficulties in measuring calprotectin. With regard to the number of patients seen by each physician, it was shown that patients do not concentrate under the responsibility of few doctors. Infliximab and adalimumab were the most commonly used biological medicines and there was a higher prescription of 5-ASA derivatives for ulcerative colitis than for Crohn's disease. Steroids were prescribed to a smaller proportion of patients in both diseases. The topics "biological therapy failure" and "new drugs" were reported as those with higher priority for discussion in medical congresses. In relation to possible differences among the country's regions, physicians from the North region reported greater difficulty in accessing complementary exams while those from the Northeast region indicated greater difficulty in accessing or releasing medicines. The data obtained through this study demonstrate the profile of specialized medical care in IBD and are a useful tool for the implementation of government policies and for the Brazilian society as a whole.

Transport Characteristics of 5-Aminosalicylic Acid Derivatives Conjugated with Amino Acids via Human H+-Coupled Oligopeptide Transporter PEPT1.

5-Aminosalicylic acid (5-ASA) is used as first line therapy for symptom remission and maintenance of inflammatory bowel disease (IBD). Because 5-ASA is well absorbed from the small intestine when orally administered, several 5-ASA formulations for selective delivery to the colon have been developed and used in clinical practice. However, its delivery efficiency to local inflamed colonic sites remains low. Intestinal H+-coupled oligopeptide transporter 1 (PEPT1) expression in the colon is low, whereas its expression is induced in the colon under chronic inflammation conditions, such as IBD. Therefore, we considered that PEPT1 would be a target transporter to improve 5-ASA delivery efficiency to local colonic lesions. We evaluated the transport characteristics of dipeptide-like 5-ASA derivatives, which were coupling glycine (Gly), lysine, glutamic acid (Glu), valine (Val) and tyrosine to amino or carboxyl group of 5-ASA, in Caco-2 cells. [3H]Glycylsarcosine (Gly-Sar) uptake into Caco-2 cells was inhibited by all 5-ASA derivatives. In addition, 5-ASA derivatives (Gly-ASA, Glu-ASA and Val-ASA), which were coupled by glycine, glutamic acid and valine to amino group of 5-ASA, were taken up in a pH- and concentration-dependent manner and their uptake was inhibited by excess Gly-Sar. Two-electrode voltage-clamp experiment using human PEPT1 expressing Xenopus oocytes showed that Gly-ASA, Glu-ASA and Val-ASA induced marked currents at pH 6.0. Taken together, these results showed that these 5-ASA derivatives are transportable substrates for PEPT1.

2082 A Rare Cause of Dyspnea in a Patient With Inflammatory Bowel Disease

INTRODUCTION: 5-aminosalicylic acid (5-ASA) and its derivatives are recommended for treatment of mild to moderate Ulcerative Colitis (UC). There have been documented reports of pulmonary toxicity with sulfasalazine, but few reported lung toxicities seen with 5-ASA components alone such as Mesalamine.1 CASE DESCRIPTION/METHODS: 68-year-old female with history of UC on Balsalazide, presented with several months of intermittent, non-radiating chest pain, orthopnea and dyspnea on exertion worsening over 4 days. 98.9 F, HR 115, BP 153/84, RR 22, SpO2 88% on room air improving to 93% with 3 L nasal cannula. Physical exam revealed bibasilar crackles. EKG and CXR were unremarkable. Extensive labs and cardiac evaluation were unremarkable. PFT had decreased DLCO 51% and BAL demonstrated lymphocytosis, moderate eosinophilia with plasma cells. HRCT showed upper lung predominant ill-defined ground-glass opacities, mild bronchial wall thickening and mosaicism. Infectious, hypersensitivity pneumonitis and rheumatologic workup was negative. She did not have worsening of her UC symptoms; CRP 7.86 mg/L (0.00-3.00 mg/L) and Fecal Calprotectin 153 ug/mg (50-200 ug/mg) were noted on admission. Interestingly, Balsalizide was started 8 weeks prior to the patient’s symptoms. With HRCT and otherwise negative lab findings, Balsalizide Induced Pneumonitis (BIP) was suspected. Balsalazide was discontinued, and steroid taper started with resolution of symptoms. DISCUSSION: Drug-induced pneumonitis (DIP) and lung toxicities from Sulfasalazine are well documented but few cases of 5-ASA derivatives have been reported. Only four case reports of DIP secondary to Mesalamine have been reported and none with Balsalazide. Diagnosis of pneumonitis is difficult in the setting of IBD due to extensive pulmonary manifestations in IBD ranging from bronchitis to pulmonary fibrosis even when IBD activity is quiessent.1These pulmonary complications typically respond well to steroids alone while DIP responds well to removal of the inciting agent.1 Our patient had an extensive work-up that was negative while the combination of the HRCT and BAL made BIP the leading diagnosis, meeting diagnostic criteria.2 The time frame of the patient’s symptoms in relation to starting Balsalazide supported the diagnosis of BIP and strengthened when Balsalazide was discontinued and prednisone started leading to improvement in symptoms.This patient illustrates the need to consider a broad differential when evaluation a patient with IBD with pulmonary complications.

P077 Tuberculosis in inflammatory bowel disease patients from a referral center in Salvador-Bahia, Brazil

BACKGROUND: In the last decade, potent immunosuppressive therapy has become the standard treatment for inflammatory bowel disease (IBD) (1). However, the increasingly use of immunomodulators associated to biological therapy—especially the inhibitors of tumor necrosis factor alpha (TNF-α)—have considerably increased the cases of tuberculosis (TB) in IBD patients (2,3). Meanwhile, Brazil is a high TB burden country, with 87,000 new cases per year, and the state of Bahia reports more than 3,600 new cases annually (4,5). METHODS: Were included IBD patients under treatment followed at a referral center from August 2017 to July 2018. The IBD was diagnosed according to the guideline criteria of was according to the criteria the European Crohn's and Colitis Organizsation. Diagnosis of latent TB infection (LTBI) was based on tuberculin skin test (TST) induration ≥5 mm without evidence of clinically manifested active tuberculosis (TB). The development of active TB, diagnosed during the treatment for inflammatory bowel disease, was based on symptoms, TST, chest X ray and laboratory finding. In addition, Sstatistical analysies was performed using the statistical software package SPSS version 21.0 for Windows. A P-value less than 0.05 was considered statistically significant. RESULTS: Of the 302 patients evaluated, 185 were submitted to screening for LTBI and 24 (12.9%) were positive. Of the total sample, 8 (2.6%) developed active TB during treatment for IBD. Six cases occurred despite theof negative screening for LTBI and 2 cases occurred even after chemoprophylaxis with isoniazid. Among 186 UC patients, 4 (2.1%) developed active TB and all cases were pulmonary TB. Two patients were under azathioprine monotherapy (?) with azathioprine and 2 were using 5-ASA derivatives without immunosuppressant. Among 116 Crohn disease (CD) patients, 4 (3.4%) developed active TB, 2 cases of pulmonary TB and 2 cases of pleural TB. All patients with CD who developed active TB were under anti-TNF therapy, 2 under treatment with infliximab monotherapy and 2 with adalimumab combotherapy associated with azathioprine. In total, 63 (20.9%) patients were under biological therapy. The frequency of active TB disease among patients exposed to anti-TNF when compared to patients not exposed was 6.3% (4/63) and 1.7% (4/239), respectively, and the difference was significant (P = 0.047) between those groups. The median time between initiation of anti-TNF therapy and the diagnosis of TB was 19 months (range: 3.0–45.0). CONCLUSION(S): The frequency of latent TB in our center is comparable to the frequency described in IBD patients from endemic countries. It was observed a high frequency of active TB in IBD patients under anti-TNF therapy from a reference center in Brazil. ACKNOWLEDGMENT: Fellowship Program from University of the State of Bahia (PICIN UNEB).

Management of major organ involvement of Behçet’s syndrome: a systematic review for update of the EULAR recommendations

To assess the efficacy and safety of treatment modalities for major organ involvement of Behçet's syndrome (BS), in order to inform the update of the EULAR recommendations for the management of BS. A systematic literature review of all randomized controlled trials, controlled clinical trials, or open label trials assessing eye, vascular, nervous system or gastrointestinal system involvement of BS was performed. If controlled trials were not available for answering a specific research question, uncontrolled studies or case series were also included. We reviewed the titles and abstracts of 3927 references and 161 studies met our inclusion criteria. There were only nine randomized controlled trials. Observational studies with IFN-α and monoclonal anti-TNF antibodies showed beneficial results for refractory uveitis. Meta-analysis of case-control studies showed that immunosuppressives decreased the recurrence rate of deep vein thrombosis significantly whereas anticoagulants did not. CYC and high dose glucocorticoids decreased mortality in pulmonary arterial aneurysms and postoperative complications in peripheral artery aneurysms. Beneficial results for gastrointestinal involvement were obtained with 5-ASA derivatives and AZA as first line treatment and with thalidomide and/or monoclonal anti-TNF antibodies in refractory cases. Observational studies for nervous system involvement showed improved outcome with immunosuppressives and glucocorticoids. Meta-analysis of case-control studies showed an increased risk of developing nervous system involvement with ciclosporin-A. The majority of studies related to major organ involvement that informed the updated EULAR recommendations for the management of BS were observational studies.

Management of colonic diverticular disease in the third millennium: Highlights from a symposium held during the United European Gastroenterology Week 2017

Diverticulosis is a common anatomical condition, which appears to be age-dependent. Individuals who develop chronic gastrointestinal symptoms or complications are referred to as having diverticular disease. Although the diagnosis of this condition can be relatively straightforward, randomized controlled trials are scarce and management often follows tradition rather than principles of evidence-based medicine. This report deals with the topics discussed during a symposium held during the United European Gastroenterology Week (Barcelona, October 2017). During the meeting, the role of dysbiosis in the pathogenesis of diverticular disease and its treatment were thoroughly discussed, by examining the efficacy and mechanisms of action of the currently used drugs. Recent studies have shown the presence of dysbiosis in patients with diverticular disease and suggest an imbalance in favor of bacteria with pro-inflammatory and pathogenetic potential. These microbiota changes correlate with mucosal immune activation, mirrored by a marked increase of macrophages in colonic mucosa, both in the diverticular region and at distant sites. The low-grade inflammation, driven by bacteria-induced immune activation, could be involved in the pathophysiology of symptoms. As a consequence, pharmacological approaches targeting enteric bacteria (with poorly absorbed antibiotics, like rifaximin, or probiotics) or intestinal inflammation (with 5-ASA derivatives or rifaximin) have shown capability of controlling symptoms and also preventing complications, albeit more research is needed to establish the optimal regimen (daily dose and duration) of therapy. Well-designed randomized-controlled trials (RCTs), including homogeneous populations of patients, are therefore needed. The future of management of many GI diseases, including symptomatic uncomplicated diverticular disease, will rely on the so-called ‘microbiota-directed therapies’.

Interstitial Nephritis in a Patient with Inflammatory Bowel Disease

Tubulointerstitial nephritis in patients with inflammatory bowel disease has been linked to the use of 5-ASA derivatives. Various aspects of this theory have been challenged with a potential role for the underlying autoimmune disorder. Steroids are the mainstay of treatment and mycophenolate mofetil might be an effective alternative. We report a patient who responded well to mycophenolate despite continuing mesalamine, the suspected offending agent.

Management of Inflammatory Bowel Disease in the Caribbean

Introduction: Inflammatory Bowel Disease (IBD) has been reported in several islands of the English speaking Caribbean. Limited resources in the region may affect the clinical management of the disease. We report the management preferences of physicians practicing in the English speaking Caribbean. Methods: Members of the Association of West Indian Gastroenterologists who currently practice in the Caribbean were sent on online survey. Members were asked a series of questions about their training and experience and random questions about their practice habits when managing patients with Ulcerative Colitis (UC) and Crohn's Disease (CD). The survey consisted of 30 questions. Each member was allowed one response. All responses were kept confidential. Results: Sixteen physicians responded to the survey. Twelve were practicing in the Caribbean at the time of the survey. Of those physicians; 5 practiced in Jamaica, 3 in Bahamas, 2 in Barbados, 1 in Trinidad and Tobago and 1 in Bermuda. Physicians were asked about their use of non-invasive markers of intestinal inflammation. Seventy five (75%) of physicians did not utilize fecal Calprotectin and fecal Lactoferrin to monitor their patients with IBD, although its use may prevent the need for costly endoscopic procedures. When initiating thiopurines, 63% of physicians ordered thiopurine methltransferase (TPMT) enzyme activity testing and 56% utilized thiopurine metabolite levels when evaluating dosing efficacy. Patients diagnosed with long-standing (> 10 years) pancolitis, in clinical remission, were routinely offered surveillance colonoscopies every 2 years, with a minority of physicians (25%) opting for every 3 years. Physicians were just as likely to perform random biopsies of the entire colon (40%) versus four quadrant biopsies every 10 cm (46.7%) when performing surveillance colonoscopies in patients with long standing UC even though chromoendoscopy is not widely available. Only 37% of IBD patients starting immune suppressive therapy are routinely vaccinated. While the majority of physicians (75%) will start 5-aminosalycilic acid (5-ASA) derivatives as initial therapy for mild to moderate UC, 41% will add steroid therapy for a clinical relapse before escalating therapy. Only 12.5% of physicians do not start immunomodulaters when initiating biologic agents. When there is a diminished response to biologics, most physicians will first check for antibodies (40%), before either increasing the dose (26.7%) or shortening the interval (20%). When patients hospitalized for a flare, prophylactic anticoagulation for deep vein prophylaxis is commonly initiated (60%). Conclusion: The earliest reports of IBD in the Caribbean were published in 1979 by Professors Courtenay Bartholomew and Alan Butler in Trinidad and Tobago. Since then epidemiological data has also been reported in Jamaica and Barbados. This is the first report, that we are aware of, describing the practice habits of physicians that manage IBD in the Caribbean. The management of IBD can be expensive, and heavily influences the clinical decisions that a physician must make. Those cases of moderate to severe disease, particularly in young people, that would warrant the use of biologic therapy, must often be treated with Thiopurines and steroids. Suboptimal treatment is less likely to result in sustained remission which translates in to frequent relapses, hospitalizations and surgery, all of which places greater demands on limited resources. More long term data is needed to determine outcomes so that resources can be better utilized to prevent sequelae of inadequately treated disease.

Unusual Case of Febrile Pleuropericarditis: A Potentially Life-threatening Side Effect of Balsalazide

Purpose: Ulcerative colitis (UC) is an idiopathic chronic inflammatory disorder that involves the rectum and the colon. The treatment typically involves inducing remission followed by the administration of maintenance medications to prevent relapse. One class among the drugs used for both remission and maintenance is the 5-aminosalicylates (5-ASAs). We present a rare case of febrile pleuropericarditis, a potentially life-threatening side effect of 5-ASA derivatives, which resolved after cessation of balsalazide. A 36-year-old Caucasian male with UC presented with 2-week history of fever (as high as 102°F), fatigue, shortness of breath and worsening right-sided pleuritic chest pain. His most recent UC flare had been 6-8 weeks prior to admission, treated with a prednisone taper and maintained on balsalazide. Upon admission, CT chest revealed right pleural effusion with possible underlying infiltrate. The initial diagnosis was community acquired pneumonia and the patient was started on levofloxacin. The patient continued to complain of chest pain and developed daily fevers as high as 103.2°F despite broadened antimicrobial coverage. An extensive work up, including thoracentesis and pericardiocentesis, was initiated to evaluate for infectious, autoimmune/inflammatory and malignant conditions. All cultures, cytology, and laboratory results were negative. For his symptomatic pleuropericarditis, the patient was started on indomethacin which did not improve his symptoms. At this point, it was believed that his symptoms were secondary to balsalazide use and this was discontinued. He rapidly and completely defervesced, and his symptoms significantly improved. He was re-challenged later on with balsalazide which resulted in reoccurrence of fever and pleuritic chest pain within several days. Pericarditis and pleuropericarditis have been reported as rare, but potentially life-threatening side effects of 5-ASA therapy. As a 5-ASA prodrug, balsalazide might be expected to share the same class effect, but to date has only been reported in association with afebrile pericarditis in one case report. We believe we have identified a very rare case of febrile pleuropericarditis associated with balsalazide therapy. Our patient had partial and temporary relief of chest pain and dyspnea with fluid removal from the chest and pericardium, and only minimal response to indomethacin. His symptoms and high fevers did not resolve until cessation of balsalazide. In conclusion, this case illustrates a rare side effect of balsalazide, easily overlooked, which any physician should consider in his/hers differential diagnosis on a patient with IBD on 5-ASA derivatives.

A survey of current practices used to maintain surgically induced remission following intestinal resection for Crohn’s disease

Post-operative Crohn's disease (CD) recurrence is common after intestinal resection. The European Crohn's and Colitis Organization has issued guidelines regarding the optimal post-operative management of patients who have undergone intestinal resection for CD. The current study aims to assess the current adjuvant therapy practices of colorectal surgeons and gastroenterologists. An electronic-based survey was sent to members of the Association of Coloproctology of Great Britain and Ireland and the Irish Society of Gastroenterology. One hundred twenty-five surgeons and gastroenterologists responded. Gastroenterologists more frequently assessed for pre-clinical recurrence with serum inflammatory markers (97 vs. 51%, P < 0.001), faecal calprotectin (30 vs. 10%, P = 0.008) and ileocolonoscopy (67 vs. 23%, P < 0.001), while surgeons more frequently performed a CT scan (23 vs. 6%, P = 0.037). The majority of respondents estimated the 1-year endoscopic recurrence to be 10-25%, and 36% of respondents offered prophylaxis to all post-operative patients. Budesonide (8 vs. 4%, P = 0.006) and azathioprine/mercaptopurine (60 vs. 33%, P < 0.001) were more often prescribed for high-risk patients, while imidazole antibiotics (11 vs. 5%, P < 0.001) and 5-ASA derivatives were more often prescribed for low-risk patients (51 vs. 14%, P < 0.001). Currently, surgeons and gastroenterologists involved in the peri-operative care of patients with CD underestimate the risk of recurrence following intestinal resection and under-utilize ileocolonoscopy to tailor adjuvant therapy.

Review article: remission rates achievable by current therapies for inflammatory bowel disease

New medical therapies have improved outlook in inflammatory bowel disease but published impact on surgical rates has been modest suggesting that many patients are still not attaining remission. To review remission rates with current medical treatments for inflammatory bowel disease. We searched MEDLINE (source PUBMED, 1966 to January, 2011). Induction and maintenance of remission was observed in 20% (range, 9-29.5%) and 53% (range, 36.8-59.6%) of ulcerative colitis (UC) patients treated with oral 5-ASA derivatives. Induction of remission was noted in 52% (range, 48-58%) of Crohn's disease (CD) patients and 54% of UC patients treated with steroids in population-based cohorts. Maintenance of remission was reported in 71% (range, 56-95%) of CD patients on azathioprine over a 6-month to 2-year period and in 60% (range, 41.7-82.4%) in UC at 1 year or longer. Induction and maintenance of remission was noted in 39% (range, 19.3-66.7%) and 70% (range, 39-90%) of CD patients on methotrexate over a 40-week period. Induction of remission was reported in 32% (range, 25-48%), 26% (range, 18-36%) and 20% (range, 19-23%) of CD patients on infliximab, adalimumab or certolizumab pegol, respectively. The corresponding figures were 45% (range, 39-59%), 43% (range, 40-47%) and 47.9% at weeks 20-30 among initial responders. Induction of remission was observed in 33% (range, 27.5-38.8%) and 18.5% of UC patients on infliximab or adalimumab, respectively. Maintenance of remission was noted in 33% (range, 25.6-36.9%) of UC patients on infliximab at week 30. Approximately one-fifth of CD and UC patients treated with biologicals require intestinal resection after 2-5 years in referral-centre studies. In the era of biologics, the proportion of patients with inflammatory bowel disease not entering remission remains high.

Management of Inflammatory Bowel Diseases during Pregnancy

Inflammatory bowel diseases (IBD) have a high prevalence in younger patients with child-bearing potential. Usually, pregnancies in women with IBD will develop normally, if the patient is in remission or has minor disease activity at the time of conception. In contrast, the frequency of normal pregnancies is significantly reduced and the frequency of adverse outcomes like preterm birth or miscarriage is increased, when conception occurs in phases with active IBD. Therefore, it is generally recommended to women with IBD to conceive at a time with minor disease activity or in remission. IBD patients who plan to become pregnant or are pregnant should be treated adequately. Currently, it is widely accepted that the treatment of IBD with corticosteroids and 5-ASA derivatives does not increase the risk of malformations or adverse outcomes in pregnant IBD patients. However, a slight increase in the number of pre-term deliveries or reduced birth weight is observed. More recently, it has also been appreciated that azathioprine and 6-MP and presumably also infliximab and other TNF-α blockers can be safely used during pregnancy in IBD, as no significant increase of malformations, miscarriages or adverse pregnancy outcomes is observed. Information on cyclosporine and tacrolimus during pregnancy is scarcer, but it may be continued or started in some situations if clinically needed. Methotrexate is contraindicated, as this drug is known to significantly increase the risk of malformations and spontaneous abortion. Patients, who wish to nurse their babies, may be treated with steroids and 5-ASA derivatives without a significantly increased risk for the newborn.

W1970 Systematic Administration of 5-ASA Derivatives During Remissions for More Than 9 Months/Year Seems to Protect Patients with Longstanding Ulcerative Colitis Against Colorectal Cancer

W1970 Systematic Administration of 5-ASA Derivatives During Remissions for More Than 9 Months/Year Seems to Protect Patients with Longstanding Ulcerative Colitis Against Colorectal Cancer

W1101 Differential Effects of 5-ASA Derivatives 4-ASA, 3-ASA and N-Acetyl-5-ASA On Cell Cycle and Replication Fidelity in Colon Epithelial Cells

W1101 Differential Effects of 5-ASA Derivatives 4-ASA, 3-ASA and N-Acetyl-5-ASA On Cell Cycle and Replication Fidelity in Colon Epithelial Cells

Synthesis and theoretical calculations of 5‐aminosalicylic acid derivatives as potential analgesic agents

5‐Aminosalicylic acid is one of the drugs most commonly used for inflammatory bowel disease treatment, although its use is limited due to side effects. The aim of this work was to synthesize four 5‐ASA derivatives (1–4) and analyze their pharmacological effects. The compound structures were elucidated by spectral (IR and 1H and 13C‐NMR) analysis, and their analgesic effects and lethal doses 50 (LD50) were evaluated in the mouse model. In addition, their Log Ps and affinities for both cyclooxygenase enzymes (COX I and COX II) were evaluated through theoretical calculations.All compounds showed analgesic activities from 0.1 mg/Kg to 16 mg/Kg in the mouse model. The imides showed more affinity by COX enzymes and their Log Ps were the highest. The docking calculations showed that all compounds have good affinities for COX I and COX II ((1 ?M), making ????, van der Waals interactions and hydrogen bonds. The toxicities of all compounds were low, judging by the LD50.Finally, the docking analysis show that the compounds act on COX enzymes and their analgesic effects could be mediated in part by the inhibition of these enzymes.

Current practice in management of Crohn's disease in Wales

Crohn's disease (CD) demonstrates great heterogeneity in its presentation and severity. Management of CD is similarly diverse but the aim remains the same--remission of disease activity and improvement of health related quality of life (HR-QoL). Treatment options include steroids, 5-ASA derivatives, immunomodulators and surgery. The aim of this study was to define the variation in practice of consultant gastroenterologists and colorectal surgeons treating CD in Wales. Consultant gastroenterologists and colorectal surgeons treating CD in Wales were sent a questionnaire aimed at determining their current practice and their responses were analysed. Eighty-eight consultants--46 (52%) gastroenterologists and 42 (48%) surgeons-- were invited to participate in the survey. Sixty-one (69%) of them responded. Coherent practice was seen across Wales, especially with respect to diagnosis of CD in line with British Society of Gastroenterology guidelines. Variation was detected in disease severity assessment and some aspects of management. Practice in Wales is in line with the guidelines for managing CD. While the diagnostic process follows a standard approach, variations exist in treatment and monitoring of disease. Validated disease measurement instruments are seldom used in routine practice. Disease assessment tools need to be simpler to use if they are to help objective measurement of disease activity and treatment decisions.

Synthesis and Theoretical Calculations of 5-Aminosalicylic Acid Derivatives as Potential Analgesic Agents

5-Aminosalicylic acid is one of the drugs most commonly used for inflammatory bowel disease treatment, although its use is limited due to side effects. The aim of this work was to synthesize four 5-ASA derivatives (1-4) and analyze their pharmacological effects. The compound structures were elucidated by spectral (IR and 1H and 13C-NMR) analysis, and their analgesic effects and lethal doses 50 (LD50) were evaluated in the mouse model. In addition, their Log Ps and affinities for both cyclooxygenase enzymes (COX I and COX II) were evaluated through theoretical calculations. All compounds showed analgesic activities from 0.1 mg/Kg to 16 mg/Kg in the mouse model. The imides showed more affinity by COX enzymes and their Log Ps were the highest. The docking calculations showed that all compounds have good affinities for COX I and COX II ( identical with 1 microM), making pi-pi, van der Waals interactions and hydrogen bonds. The toxicities of all compounds were low, judging by the LD50. Finally, the docking analysis show that the compounds act on COX enzymes and their analgesic effects could be mediated in part by the inhibition of these enzymes.