Oral Mesalamine Research Articles

Tofacitinib: Janus Bifrons in Ulcerative Colitis Treatment

Tofacitinib: Janus Bifrons in Ulcerative Colitis Treatment

Medication adherence and persistence in the treatment of Canadian ulcerative colitis patients: analyses with the RAMQ database.

BackgroundAlthough high non-adherence to medication has been noticed for ulcerative colitis (UC), little is known about adherence to mesalamine treatments and determinants that can predict adherence. The objective of this study was to assess adherence and persistence to mesalamine treatments and their potential determinants in mild to moderate UC patients in a real-life setting in Quebec, Canada.MethodsA retrospective prescription and medical claims analysis was conducted using a random sample of mesalamine users with UC. For inclusion, patients were required to initiate an oral mesalamine treatment between January 2005 and December 2009. Patients with a diagnosis of Crohn’s disease were excluded. Treatment adherence (medication possession ratio [MPR]) and persistence were evaluated over a 1-year period after the index prescription using the Kaplan-Meier method with log-rank test and stepwise regression to identify potential determinants.ResultsA sample of 1,681 of the new oral mesalamine users (mean age = 55.3) patients was obtained. Overall, the percentage of patients with a MPR of 80% or greater at 12 months was 27.7%, while persistence was 45.5%. Among patients treated with mesalamine delayed/extended-release tablets (Mezavant®), adherence and persistence were 40.9% and 71.9%, respectively. Predictors of high adherence included, male gender (OR=1.3; 95% confidence interval [CI]=1.1–1.6), older age (>60 years; OR=1.6; 95% CI=1.3–2.0) and current use of corticosteroids (OR=1.4; 95% CI=1.1–1.8). Predictors of high persistence included male sex (OR=1.4; 95% CI=1.1–1.7), current use of corticosteroids (OR=1.4; 95% CI=1.1–1.7) and presence of hypertension or respiratory diseases (OR=1.2; 95% CI=1.01–1.55).ConclusionsThe majority of patients with UC exhibited low adherence and persistence to mesalamine treatments. Various determinants of improved adherence and persistence were identified.

Noninfectious interstitial lung disease during infliximab therapy: Case report and literature review

Pulmonary abnormalities are not frequently encountered in patients with inflammatory bowel diseases. However, lung toxicity can be induced by conventional medications used to maintain remission, and similar evidence is also emerging for biologics. We present the case of a young woman affected by colonic Crohn's disease who was treated with oral mesalamine and became steroid-dependent and refractory to azathioprine and adalimumab. She was referred to our clinic with a severe relapse and was treated with infliximab, an anti-tumor necrosis factor α (TNF-α) antibody, to induce remission. After an initial benefit, with decreases in bowel movements, rectal bleeding and C-reactive protein levels, she experienced shortness of breath after the 5(th) infusion. Noninfectious interstitial lung disease was diagnosed. Both mesalamine and infliximab were discontinued, and steroids were introduced with slow but progressive improvement of symptoms, radiology and functional tests. This represents a rare case of interstitial lung disease associated with infliximab therapy and the effect of drug withdrawal on these lung alterations. Given the increasing use of anti-TNF-α therapies and the increasing reports of pulmonary abnormalities in patients with inflammatory bowel diseases, this case underlines the importance of a careful evaluation of respiratory symptoms in patients undergoing infliximab therapy.

Isolated fever induced by mesalamine treatment

Adverse reactions to mesalamine, a treatment used to induce and maintain remission in inflammatory bowel diseases, particularly ulcerative colitis, have been described in the literature as case reports. This case illustrates an unusual adverse reaction. Our patient developed an isolated fever of unexplained etiology, which was found to be related to mesalamine treatment. A 22-year-old patient diagnosed with ulcerative colitis developed a fever with rigors and anorexia 10 d after starting oral mesalamine while his colitis was clinically resolving. Testing revealed no infection. A mesalamine-induced fever was considered, and treatment was stopped, which led to spontaneous resolution of the fever. The diagnosis was confirmed by reintroducing the mesalamine. One year later, this side effect was noticed again in the same patient after he was administered topical mesalamine. This reaction to mesalamine seems to be idiosyncratic, and the mechanism that induces fever remains unclear. Fever encountered in the course of a mesalamine treatment in ulcerative colitis must be considered a mesalamine-induced fever when it cannot be explained by the disease activity, an associated extraintestinal manifestation, or an infectious etiology.

Fecal Bacteriotherapy in a 6 Year Old Patient With Ulcerative Colitis and Clostridium Difficile

Inflammatory bowel disease (IBD) is thought to be a disorder of the innate and reactive immune system, and its interaction with the gastrointestinal microbiome. A growing body of literature supports the use of fecal bacteriotherapy in eradicating Clostridium difficile (C. diff) infections. Its use in IBD has been reported but not established. 20-25% of IBD patients present in childhood. Current available IBD therapies pose significant challenges, especially in young children with IBD, due to their side effects and route of administration. We discuss our experience with fecal bacteriotherapy in a 6 year old child with relapsing Ulcerative Colitis (UC) and recurrent C. diff infection. A 6 year old female was diagnosed with UC after presenting with bloody stools, abdominal pain, anemia and elevated ESR. Initial colonoscopy showed pancolitis and a normal terminal ileum. Due to lack of response to oral mesalamine and steroid dependence, azathioprine was started with rectal mesalamine and rectal steroids. Allopurinol was added after breakthrough symptoms and severe anemia. She continued to have intermittent moderate symptoms (blood, diarrhea) at 1 year out from diagnosis. C. diff antigen and toxin were present, and persisted despite treatment with metronidazole and vancomycin. The family was interested in pursuing fecal bacteriotherapy prior to initiating further antibiotic courses and infliximab. Approval was obtained from bioethics committee. Her mother was the stool donor and was screened for stool infections, viral hepatitis and HIV. At baseline, a sigmoidoscopy showed no pseudomembranes, but microscopic moderate chronic active colitis. A nasogastric (NG) tube was placed. Fresh donor stool was mixed with saline then superfiltrated to 30 cc suspension. The suspension was instilled via NG tube uneventfully post procedure, after which it was removed and the patient discharged home. Symptoms and stool inflammatory markers were followed from baseline to 16 weeks post procedure. No treatments aside from azathioprine and allopurinol were used. Stool calprotectin decreased from 504 at baseline to 76 by week 12. C.diff antigen and toxin were cleared by 3 weeks. Microbiome analysis of the donor stool and the patient's stool before and at 3 periods after bacteriotherapy are pending and will be finalized shortly. We describe a case of successful fecal bacteriotherapy for a child with recalcitrant UC and C diff. The implication of the improved calprotectin will be further explored with reducing her current medications. The relative ease, tolerability and success of the procedure should encourage further study.

Systemic Secondary Amyloidosis in a 70-Year Old Patient with Crohnʼs Disease: Treatment with Oral Budesonide

Purpose: Systemic secondary amyloidosis is a rare but potentially lethal complication of Crohn's disease (CD). It was reported that renal involvement was the most common manifestation in approximately 1% of patients with CD. A variety of therapeutic modalities have been reported, including azathioprine, colchicine, dimethyl sulfoxide, elemental diets and anti-tumor necrosis factor-alpha agents. However, there is still no definitive treatment for secondary amyloidosis with CD. Methods: This is a retrospective chart review. Patient's clinical visit note, procedure and pathology results were reviewed. Clinical Case: A 70-year-old man was diagnosed with colonic CD complicated with a history of perianal fistula since the age of 20 non intermittent prednisone and 5-ASAs. He was also found to have systemic secondary amyloidosis on the kidney biopsy two years ago due to hypertension and elevated creatinine. He was referred to our IBD Clinic in late 2009 for watery diarrhea 10 times per day and bloating. The first colonoscopy showed segmental colitis with edema and multiple colonic strictures distributed in ascending, transverse, descending and sigmoid colons which required endoscopic balloon dilatation. Ileocecal valve was significantly deformed, and not traversible via a pediatric colonoscope. Biopsy showed perivascular amyloidosis on the background of chronic active colitis in all colonic and rectal samples (Figure 1). He had an unsuccessful trial of colchicine from his nephrologist due to adverse effects, and decided not to use immunomodulators and anti-TNF alpha agents due to the concern “malignant potential”. Instead, he was treated with oral budesonide 3mg TID and oral mesalamine 1 gram BID. A repeat colonoscopy three months later showed no active disease, but mucosal scars, and mild active ileitis. Biopsy showed chronic active inflammation in the terminal ileum and rectum with resolution of mucosal amyloid deposits. Clinically patient was doing well on the regimen regarding the frequency of his bowel movements. Serum creatinine and proteinuria have been stabilized.Figure 1: Congo red stain of the colon (A) and rectal (B) biopsy demonstrates submucosal perivascular amyloid deposit (orange colored staining) [congo red, X100].Conclusion: We believe that oral budesonide together with oral 5-ASA agent may be considered a part of medical treatment armamentaria for secondary systemic amyloidosis of CD.

Efficacy of Oral Mesalamine Monotherapy (5-ASA) versus Combination Oral Mesalamine Plus Proton Pump Inhibitor (5-ASA/PPI) Therapy in the Treatment of Ulcerative Colitis (UC)

Efficacy of Oral Mesalamine Monotherapy (5-ASA) versus Combination Oral Mesalamine Plus Proton Pump Inhibitor (5-ASA/PPI) Therapy in the Treatment of Ulcerative Colitis (UC)

Primary Gallbladder Carcinoma in a Pregnant Patient with Crohnʼs Disease Complicated with Gallbladder Involvement

Purpose: Primary gallbladder (GB) carcinoma and Crohn's disease (CD) of the GB are individually rare. We present a case of a pregnant woman with CD found to have GB involvement and primary GB carcinoma. Case: A 34-year-old female at 6 weeks gestation with a 21 year history of CD of uncertain extent presented with 3 months of diarrhea, urgency, and abdominal pain. Her disease had been indolent for the majority of her life. She was adherent to her medications, mesalamine and mercaptopurine, as needed at times of symptoms. Sigmoidoscopy showed mild patchy colitis of the descending and sigmoid colon with rectal sparing. Pathology showed moderately active chronic colitis with crypt distortion and cryptitis without granuloma. She was started on oral and topical mesalamine. Initial labs included abnormal alkaline phosphatase 515 U/L, AST 96 U/L, and ALT 181 U/L. Further labs included a negative anti-mitochondrial antibody (AB), anti-smooth muscle AB, celiac and viral hepatitis serologies and anti-nuclear AB. A non-contrast MRCP was obtained revealing two hypointense smooth margined masses with small stalks in the neck and fundus of the GB, 1.4 × 1.8 cm and 1.4 × 2.3 cm, respectively. No GB wall thickening, cholilithiasis, ductal dilation, strictures, or liver parenchymal abnormalities were present. Laparoscopic cholecystecomy was performed at 18 wks gestation. Histology revealed a poorly differentiated adenocarcinoma of the GB with invasion through the muscularis propria and an adjacent tubulovillous adenoma with highgrade dysplasia without nodal involvement (stage pT2N0). Additionally, there was widespread epithelial dysplasia in the gallbladder with acute superficial inflammation, transmural chronic inflammation with numerous plasma cells and one granuloma consistent with CD. Muscularis propria invasion prompted partial liver resection and portal lymphadenectomy, revealing matted lymph nodes in the porta hepatis positive for metastatic carcinoma (stage pT2N1). Liver tissue was negative for primary sclerosing cholangitis. Conclusion: Seven cases of CD involving the GB and 3 cases of primary GB carcinoma in CD have been published. This is the only case that describes both. Common features in CD of the GB include acute cholecystitis, ileal involvement, and presence independent of active intestinal disease. Common features in CD patients with GB malignancy include younger age of detection, a long history of CD, extensive colonic and ileal involvement, and absence of cholelithiasis. Adnomatous GB polyps and pregnancy is specific to this case. The role of CD in the development of GB malignancy is not well understood; however, longstanding immunosuppression is implicated.

Update on the management of ulcerative colitis: treatment and maintenance approaches focused on MMX® mesalamine

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that typically manifests as diarrhea, abdominal pain, and bloody stool. Complications, such as colorectal cancer and extraintestinal manifestations, may also develop. The goals of management are to induce and maintain clinical remission and to screen for complications of this disease. Mesalamine is a 5-aminosalicylic acid compound that is the first-line therapy to induce and maintain clinical remission in patients with mild-to-moderate UC. For patients who are refractory to mesalamine or have more severe disease, steroids, azathioprine/mercaptopurine, cyclosporine, or infliximab may be used, induce and/or maintain remission. The various formulations of mesalamine available are primarily differentiated by the methods of delivery of the active compound of the drug to the colon. Mesalamine with Multi-Matrix System® (MMX) technology (Cosmo SpA, Milan, Italy) is an oral (1.2 g), once-daily tablet formulation of mesalamine used for the treatment of UC (Lialda® or Mezavant®, Shire Pharmaceuticals Inc, Wayne, PA). In clinical studies, MMX mesalamine (taken as a once-daily dose of 2.4 or 4.8 g) effectively induced and maintained clinical remission in patients with active mild-to-moderate UC. The overall safety profile of MMX mesalamine is similar to other oral mesalamine formulations. The use of such once-daily formulations has led to intense interest in whether simplified pill regimens can improve patient adherence to mesalamine therapy.

Once daily oral mesalamine compared to conventional dosing for induction and maintenance of remission in ulcerative colitis: A systematic review and meta-analysis

We systematically reviewed and compared the efficacy and safety of once daily (OD) mesalamine to conventional dosing for induction and maintenance of remission in ulcerative colitis (UC). A literature search to January 2012 identified all applicable randomized trials. Study quality was evaluated using the Cochrane risk of bias tool. The GRADE criteria were used to assess the overall quality of the evidence. Studies were subgrouped by formulation for meta-analysis. Eleven studies that evaluated 4070 patients were identified. The risk of bias was low for most factors, although five studies were single-blind and one was open-label. No difference was observed between the dosing strategies in the proportion of patients with clinical remission (relative risk [RR] 0.95; 95% confidence interval [CI] 0.82-1.10), clinical improvement (RR 0.87 95% CI 0.68-1.10), or relapse at 6 (RR 1.10; 95% CI 0.83-1.46) or 12 months (RR 0.92; 95% CI 0.83-1.03). Subgroup analyses showed no important differences in efficacy. No significant difference was demonstrated in rates of medication adherence or adverse events between OD and conventional dosing. OD mesalamine appears to be as effective and safe as conventional dosing for both the treatment of mild to moderately active UC and for maintenance of remission in quiescent UC. The failure to demonstrate a superior rate of adherence to OD dosing may be due to the high rate of adherence observed in the clinical trials environment. Future research should assess the value of OD dosing in community settings.

Cost Utility of Inflammation-Targeted Therapy for Patients With Ulcerative Colitis

Oral mesalamine drugs are frequently used to treat patients with mild-to-moderate ulcerative colitis (UC). However, these drugs are costly, and long-term adherence is poor. We compared the cost utility of inflammation-targeted, intermittent therapy with that of universal, continuous maintenance therapy with mesalamine agents for patients with mild-to-moderate UC. We developed a Markov cohort model that simulated a population of adult patients with newly diagnosed, quiescent UC after induction of remission with mesalamine agents. We obtained model inputs from the literature. The perspective taken was that of a short-term payer (health insurance provider) during a 5-year time period. We modeled 3 treatment strategies: symptom-targeted treatment (treatment for symptomatic disease flares only, SYMPT), continuous mesalamine maintenance for all patients (CONT, the current standard of care), and inflammation-targeted treatment (mesalamine therapy for only patients with a stool sample positive for an inflammatory marker, INFLAM). We measured disease flares, quality-adjusted life years (QALYs), costs (2009 U.S. dollars), and incremental cost-effectiveness ratios. INFLAM was the least costly strategy (cumulative per-patient cost of $22,798), compared with $24,378 for the SYMPT and $25,621 for the CONT strategies. Despite the lower cost, INFLAM was comparable to SYMPT and CONT in effectiveness (4.4986 vs 4.5014 QALYs, respectively), making INFLAM the optimal strategy. Several variables were found to be important in sensitivity analysis; the CONT strategy was optimal only if the cost of mesalamine drugs was markedly reduced. Inflammation-targeted treatment of patients with UC is effective and costs less than continuous treatment of all patients with mesalamine, the current standard of care. Prospective trials of inflammation-targeted treatment are warranted.

Can oral 5-aminosalicylic acid be administered once daily in the treatment of mild-to-moderate ulcerative colitis? A meta-analysis of randomized-controlled trials

Several trials have demonstrated that oral delayed-release mesalamine might be administered once daily. We aimed to conduct a meta-analysis to investigate this. A comprehensive and multiple-source literature search was carried out. Only randomized-controlled trials (RCTs) were investigated by comparing a once daily-dosing regime with a divided (twice or thrice daily)-dosing regime of oral delayed-release mesalamine formulations for induction or maintenance of remission in patients with mild-to-moderate ulcerative colitis. The quality of RCTs was assessed using the Jadad scores. Meta-analysis of pooled odds ratios was carried out using Review Manager 5.1. Nine RCTs were finally included. With regard to meta-analyses for induction trials, there were no significant differences for all comparisons between the once daily and the divided groups, including maintenance of just clinical remission (P=0.52) and just endoscopic remission (P=0.23), maintenance of combined clinical and endoscopic remission (P=0.78), and the overall incidence of adverse events (P=0.61). With regard to meta-analyses for maintenance trials, there were also no significant differences for all comparisons between once daily and divided groups, including maintenance of just clinical remission (P=0.73) and just endoscopic remission (P=0.43), maintenance of combined clinical and endoscopic remission (P=0.43), the overall incidence of adverse events (P=0.12) as well as compliance with the prescribed medication (P=0.34). The present work showed that oral delayed-release mesalazine administered as a single or a divided dose demonstrated a good safety profile, which was well tolerated and effective as either maintenance or induction treatment. High clinical and/or endoscopic remission rates can be achieved with once-daily dosing.

Sa2048 Predicting Regional Colonic Concentrations of 5-Aminosalicylic Acid (5-ASA) From Oral and Topical Therapy With Dynamic Modeling in Ulcerative Colitis

Background 5-aminosalicylate (5-ASA) formulations are approved for treatment andmaintenance of remission in mild-moderate ulcerative colitis (UC). Determination of the colonic distribution of 5-ASA from various formulations is challenging, since estimates depend on 5-ASA measurements in the serum and the urine. A dynamic model of colonic concentrations of 5-ASA after oral pH dependent delayed-release mesalamine, oral pH dependent extended delayed-release MultiMatrixSystem (MMX) mesalamine, 5-ASA enema, foam and suppositories was developed to determine the colonic pharmacokinetics of these agents. Methods Using published data, we created a computer model with STELLA software (isee, Hanover, NH). Colonic 5-ASA in the right, transverse, descending, sigmoid colon, and rectumwere estimated after once daily doses of the above formulations individually and in combination. Simulations of active mild-moderate UC, (defined as 6 bowel movements (BMs)/day), as well as UC in remission, (defined as 1 BM/day), were performed. Gastrointestinal transit times were determined using published literature modified for periods of sleep. Random distributions were used to model variations in colonic emptying. Data obtained was compared using paired Student's T Tests for difference in mean concentrations with SPSS software (IBM, Armonk, NY, USA.) Results Uneven distribution of 5-ASA was seen with both oral preparations. For UC in remission, the highest levels of 5-ASA in the right colon and transverse colon, (p-value < .01), were from oral delayed-release mesalamine (4.8 gm), in the descending colon and sigmoid colon (p-value < .01) from MMX mesalamine (4.8 gm), and from 5-ASA enema (4g) in the rectum (p-value < .01) (table 1). With active UC, sigmoid and rectal levels from both oral preparations were markedly decreased. Sigmoid levels were highest with foam (4g) (p-value < .01), and rectal levels highest with 5-ASA enema (p-value < .01) (table 1). Differences in recto-sigmoid levels of 5-ASA from enemas and suppositories (1.5g) were markedly influenced by time of BM occurrence (figure 1). For UC in remission, increasing MMX mesalamine dose to 4.8 gm daily resulted in the higher sigmoid-rectal levels compared to combination therapy of 2.4g MMX mesalamine (dose approved for maintenance of remission) with 1g/day 5-ASA enema. Conclusions This is the first dynamic model designed to overcome the difficulties of predicting colonic concentrations of oral and rectally administered 5-ASA formulations. The model suggests that compared to oral delayedrelease mesalamine, MMX mesalamine treatment results in higher 5-ASA levels in the left colon. Higher colonic levels of 5-ASA are achieved when insertion of topical 5-ASAs takes place shortly after a bowel movement. Dynamic modeling provides a rationale for further clinical studies to optimize 5-ASA treatment. Table 1: Mean colonic concentrations of 5-Aminosalicylic acid from oral and topical therapies in ulcerative colitis

1126 Prediction of Treatment Failures in Induction of Remission With Oral Mesalamine in Mild-to-Moderately Active Ulcerative Colitis

BACKGROUND: There are limited treatment options for patients with corticosteroid refractory ulcerative colitis (UC). Tacrolimus belongs to a group ofmedicines known as immunosuppressive agents. Animal models of inflammatory bowel disease and uncontrolled studies in humans suggest that Tacrolimus may be an effective medication for patients with UC. Accordingly, although almost exclusively used in trial cases, Tacrolimus has shown significant efficacy in the suppression of UC relapse. This study compared the efficacy of oral Tacrolimus vs Cyclosporine (Cs)A in patients with UC, refractory to corticosteroids. METHODS: Between January 2006 and January 2011, a total of 113 patients with UC, all corticosteroid refractory were included in this study. The patients were randomly assigned to two groups, CsA (n= 80; 40 male and 40 female, average age 34.7 ± 13.9 years) and Tacrolimus (n=33, 23 male and 10 female, average age 41.4 ± 15.7 years). Lichtiger's clinical activity index (CAI) was applied to assess UC activity and treatment efficacy. Following an initial 14 days of remission induction therapy with CsA (2mg/kg body weight/day, iv) or Tacrolimus (0.05-0.15mg/kg body weight/day), patients who achieved a CAI score of 3 or better were followed for 12 months. During the 12 months follow-up time, maintenance rate of remission was monitored by using the Kaplan-Meier graphs for survival analyses. RESULTS: In the CsA group, the average CAI scores before and after the initial two weeks of treatment were 13.1 ± 2.92 and 5.6 ± 3.35, respectively (P<0.0001). The corresponding CAI scores in the Tacrolimus group were 9.75 ± 3.27 and 5.0±3.84, respectively (P<0.01). The clinical remission rates (CAI = 3 or better) after the initial two weeks of treatment were 30.0% (24 of 80 patients) in the CsA group and 45.4% (15 of 33 patients) in the Tacrolimus group, the difference was not statistically significant (P=0.11). Further, response rates (a decrease in CAI by at least 4 points) were 77.5% (62 of 80 patients) in the CsA group and 69.7% (23 of 33 patients) in the Tacrolimus group. Again, the difference did not reach significance level (P= 0.38). Likewise, the rates of remission maintenance at 12 months were 35.2% in the CsA group and 33.7% in the Tacrolimus group. The difference did not reach significance level (P= 0.26). CONCLUSIONS: In this study involving 113 patients with UC of corticosteroid refractory background, Tacrolimus and CsA showed similar efficacy both in the rate of remission induction and maintenance of remission.

Sa1977 A Randomised, Double-Blind Study of High and Low Dose Oral Delayed-Release Mesalamine Does Not Demonstrate a Difference in Treating Mild to Moderately Active Ulcerative Colitis in Children

Sa1977 A Randomised, Double-Blind Study of High and Low Dose Oral Delayed-Release Mesalamine Does Not Demonstrate a Difference in Treating Mild to Moderately Active Ulcerative Colitis in Children

Incidence of and impact of medications on colectomy in newly diagnosed ulcerative colitis in the era of biologics

The cumulative incidence of colectomy and the impact of 5-aminosalicylates (5-ASA), azathioprine, and antitumor necrosis factor (TNF) treatment on the long-term need for surgery are unknown in ulcerative colitis (UC) in the era of biologics. This was an observational study of a referral center cohort. The cumulative incidence of UC-related colectomy was estimated using the Kaplan-Meier method. Independent predictors of surgery were identified using Cox proportional hazards regression with propensity scores adjustment. The electronic charts of 151 incident cases of UC from Nancy University Hospital, France, diagnosed between 2000 and 2008, were reviewed through January 2010. The median follow-up time per patient was 58 months. Twenty-one (14%) underwent surgery. The cumulative probabilities of colectomy were respectively 1.3% and 13.5% at 1 and 5 years from the time of diagnosis. The probability of receiving oral mesalamine at 5 years was 68.1%. The corresponding figures were 48.9% for azathioprine and 29.0% for infliximab. For corticosteroids, methotrexate, and cyclosporin these figures were 75%, 8.8%, and 11.5%, respectively. Using multivariate Cox proportional hazards regression analysis after propensity score adjustment, previous use of cyclosporin was the only independent predictor for colectomy (hazard ratio = 4.41; 95% confidence interval 1.75-1.13). About one-tenth of patients still require colectomy for UC at 5 years in the era of biologics. Oral 5-ASA, azathioprine, and anti-TNF therapy are not associated with a reduced need for colectomy.

Efficacy of Oral Mesalamine Monotherapy versus Combination Oral Mesalamine Plus Proton Pump Inhibitor Therapy in the Treatment of Ulcerative Colitis

Efficacy of Oral Mesalamine Monotherapy versus Combination Oral Mesalamine Plus Proton Pump Inhibitor Therapy in the Treatment of Ulcerative Colitis

Intestinal Mucormycosis in Crohnʼs Disease

Purpose: Mucormycosis is a rare fungal infection. Immunocompromised individuals may become infected with exposure to airborne spores. We present a rare case of gastrointestinal mucormycosis after treatment with corticosteroids in the setting of inflammatory bowel disease. A 38-year-old Caucasian female recently diagnosed with Crohn's disease presented to a local hospital with 9 months history of abdominal pain and diarrhea. Colonoscopy revealed moderately severe ulcerative ileocolonic Crohn's disease. She was placed on 40mg oral prednisone and mesalamine 3.2gm daily by her primary gastroenterologist. She had been smoking one and half packs of cigarettes. She continued prednisone 40mg for two months, when she presented to our facility with worsening of abdominal pain, hypotension and sepsis. CT scan revealed dilated small bowel loops with oral contrast leaking into the peritoneum. Emergency laparotomy was performed and she was found to have a perforated cecum at the level of ileocecal valve leading to two stage surgery for end ileostomy with resection of the cecum and terminal ileum. The surgical specimen revealed chronic active inflammation, ulceration and serositis with fibrinopurulent exudate. GMS stain was positive for fungal organisms with ribbon-like morphology suggestive of Mucormycosis. AFB stain was negative for acid-fast bacilli. Patient was started on parenteral antifungal medications with gradual improvement in her clinical condition. Mucormycosis is an often catastrophic, fulminating fungal infection, classically described in poorly controlled diabetics and profoundly immunosuppressed patients. Previously, two cases have been reported in Crohn's disease where combination therapy with anti-TNF therapy led to sinus and gastric mucormycosis. This is the first case of intestinal mucormycosis in Crohn's disease patient on long-term prednisone use. Although the approximate survival rate in mucormycosis is approximately 50%, mortality can be as high as 100% in cases of disseminated disease. In patients with high clinical suspicion for mucormycosis, the importance of early diagnosis, correction of underlying risk factors and treatment cannot be overemphasized.Figure: GMS stain of cecum mucosa, magnified ×600, showing ribbon like morphology of Mucor.

Peripheral Gangrene: An Unusual Extra Intestinal Manifestation of Ulcerative Colitis

Purpose: Introduction: Inflammatory bowel disease (IBD) is associated with multiple extra intestinal manifestations. Vascular complications including arterial and venous thrombosis or vasculitis are rare. They are more often reported with Crohn's disease rather than ulcerative colitis (UC). Here we describe a patient with UC presenting with toe gangrene. Case: A 31-year-old Caucasian man with UC for 9 years presented with two day history of pain and blue discoloration of left fifth toe. He was noncompliant with treatment which resulted in multiple flares; last one being a month prior to admission. On examination, the entire left fifth toe was dusky with dry gangrene at the tip. Peripheral pulses were normal. Systemic examination was normal except for pallor. Blood tests revealed hemoglobin of 3.9 g/dl and platelets of 792 k/μL. Patient was admitted to intensive care unit. After sending the thrombophilia work-up, the patient was started on intravenous heparin drip. Arterial duplex of aorta and lower extremities was normal. Echocardiogram did not reveal clot or vegetation. Sedimentation rate was normal and C-reactive protein was mildly elevated. Thrombophilic work-up was negative except for modest elevation in platelet count ranging from 650-900 k/μL. Vasculitic work-up was negative. Stool tests were normal. Colonoscopy revealed moderate to severe pancolitis with crypt abscesses on biopsy. He was started on oral steroids and mesalamine. The gangrene did not extend beyond the toe. Due to recurrent GI bleeding, heparin was discontinued and patient was discharged on aspirin. Discussion: Extra intestinal manifestations occur in 21-40% cases of IBD and commonly involve joints, skin, biliary tract and eyes. Thromboembolic phenomenon is rare. It can occur prior to, in conjunction with or subsequent to active bowel disease. Risk of venous thromboembolism is increased 3 fold in these patients. Arterial thrombosis is even rare. An enhanced clotting rate results from increased levels of factor V, VIII and fibrinogen and fall in antithrombin III. Increased platelets have been shown to increase thrombotic risk in UC as seen in our patient. Management of such lesions is not clearly established, although cases of resolution with prednisone and intravenous heparin have been reported. Anticoagulation can pose a risk of bleeding in the setting of active colitis and should be used with caution. Thus, it is important to note that UC is associated with widespread systemic manifestations which need to be diagnosed and treated early in order to prevent additional morbidity or mortality.

Optimization of Oral Mesalamine Therapy Leads to Clinical Improvement in Mild to Moderate Ulcerative Colitis

Purpose: The mainstay for the treatment of Ulcerative Colitis (UC) is the mesalamine family. While the exact mechanism of action of these agents is unknown, their anti-inflammatory effects in mild to moderate disease can be profound. However, in order to be functional, the active moiety must be present at the site of active UC. The technology behind the releasing mechanisms of the various oral preparations - pH dependent, time release or azo-bonded pro-drug - determines the timing and location of active drug delivery. Optimization within this class may spare the patient from escalating to more potent systemic immunosuppressive agents. Aim: To determine if switching to or adding a pH 6 releasing granulated mesalamine will improve clinical Mayo scores for mild to moderate UC. Methods: We collected demographic information on patients presenting with mild to moderate exacerbation in their disease. The clinical components of the Mayo score for UC (i.e. stool frequency, bleeding and physician assessment) were prospectively collected as well. All patients were seen 1 month and 3 months after the initial visit. There was no placebo group. The primary endpoint was improvement in Mayo score at 1 month. Secondary endpoints were improvement in Mayo score at 3, 6 and 12 months. Results: There were 127 patients who were studied between July 2009 and February 2011 with complete data for analysis of the primary endpoint. The mean age was 37.5 ± 14.9 with 61% being female and a mean number of years of disease prior to intervention of 6.5 ± 8.4. There were 25% active tobacco users as well. The disease was limited to the rectum in 27 patients (21.2%), the left colon in 48 (37.8%) and encompassed the entire colon in 31 (24.4%). The mean baseline Mayo clinical score was 4.88 ± 2.25. The score significantly improved with a mean score of 3.64 ± 2.20, p<0.001, by 1 month. This improvement persisted progressed at 3 and 6 months (mean 2.81 ± 1.94, p<0.001; mean 2.33 ± 1.82, p<0.001, respectively). The effect of the mesalamines was independent from any additional pharmacologic interventions. Conclusion: In patients with mild to moderate UC who are flaring, adding or switching to granulated mesalamine may lead to meaningful clinical improvement and may spare a patient escalation to a class of systemic immunosuppression. Further studies need to be conducted to determine how best to personalize the optimization strategies when using mesalamines on patients who have flared while on more traditional dosing schemes. Disclosure: Dr. Bosworth -- Consultant: Salix, Shire; Grant Support: Salix Dr. Scherl -- Consultant: Salix, Shire; Grant Support: Salix.