Mesalamine Suppositories Research Articles

MEDICAL, ENDOSCOPIC, AND SURGICAL THERAPIES FOR THE TREATMENT OF RECTAL CUFFITIS IN ULCERATIVE COLITIS PATIENTS WITH AN ILEAL POUCH-ANAL ANASTOMOSIS: A SYSTEMATIC REVIEW

Abstract BACKGROUND Patients who undergo ileal pouch-anal anastomosis (IPAA) without mucosectomy are left with a rectal cuff, which can develop inflammation known as cuffitis. Treatment of cuffitis typically includes mesalamine suppositories or corticosteroids, but individuals with refractory cuffitis may require advanced therapies, endoscopic intervention, or surgical intervention. The aim of this review is to summarize the existing literature regarding treatments options for cuffitis. METHODS A broad search strategy was created by a medical librarian to capture rectal cuffitis in IPAA patients. The following databases were searched: Ovid Medline® ALL, Ovid Embase, Cochrane Central Register of Controlled Trials (Wiley), and 3 indexes in Web of Science from Clarivate: Science Citation Index-Expanded, Conference Proceedings Citation Index, and BIOSIS Citation Index. A total of 1,652 citations were identified, and 836 studies remained after removal of 816 duplicates. Two reviewers screened all 836 abstracts and 241 full-text articles to determine if they were eligible for inclusion in this review. RESULTS A total of 21 studies (10 cohort studies, 9 case-series, 2 open-label clinical trials) met the inclusion criteria. Medical interventions were investigated in 15 studies (Table 1) with mesalamine being the most common (4 studies) followed by corticosteroids (3 studies), ustekinumab (3 studies), vedolizumab (2 studies), tofacitinib (1 study), and infliximab (1 study). Studies investigating mesalamine and corticosteroid use generally had larger sample sizes (ranging 4-120 patients) and showed symptomatic improvement in 51.7-100% of patients and decreases of 1.14-1.8 points in endoscopic disease activity indices. In contrast, studies investigating advanced therapies had small sample sizes (ranging 1-21 patients) and showed variable responses ranging from no clinical (tofacitinib) or endoscopic (ustekinumab, vedolizumab) improvements to clinical (ustekinumab) or endoscopic (vedolizumab) responses in 75% of patients. Endoscopic and surgical approaches were explored in 6 studies (Table 2) and included secondary mucosectomy (2 studies), endoscopic cuff resection, transanal minimally invasive surgery, endoscopic needle-knife therapy, and balloon dilation for cuffitis patients with concomitant outlet strictures (1 study each). These techniques generally resulted in resolution of symptoms but were limited by small sample sizes (ranging 3-16 patients). CONCLUSIONS Most studies evaluating therapies used to treat rectal cuffitis suggest beneficial effects of conventional mesalamine or corticosteroid-based therapies, whereas data regarding the efficacy of advanced therapies and interventional procedures are inconsistent given small sample sizes. Further research is needed to effectively characterize additional management options for this condition. Table 1. Medical therapies used for treatment of cuffitis. Abbreviations – BM: bowel movements, CRP: C-reactive protein, UST: ustekinumab, HBOT: hyperbaric oxygen therapy, mPDAI: modified Pouch Disease Activity Index, 5-ASA: 5-aminosalicylate, ESR: erythrocyte sedimentation rate, PDAI: Pouch Disease Activity Index, CGQOL: Cleveland Global Quality of Life score, IPS: Irritable Pouch Syndrome, CAI: Cuffitis Activity Index. Table 2. Endoscopic and surgical therapies used for treatment of cuffitis. Abbreviations – FISI: Fecal Incontinence Severity Index, CGQOL: Cleveland Global Quality of Life score, PDAI: Pouch Disease Activity Index, BM: bowel movements.

Mesalamine induced hepatotoxicity. Is mesalamine safe?

Dear Editor: Mesalamine is a medication used widely in the treatment of patients with inflammatory bowel disease. Although mesalamine is considered safe, hepatotoxicity has been reported with an incidence of 0-4%. We present the clinical picture of a patient with hepatotoxicity due to mesalamine. A 79-year-old woman in the context of chronic diarrhea, a left-sided ulcerative colitis diagnosis was made, and treatment was initiated with oral mesalamine 4 g per day, and mesalamine suppositories. Before starting treatment, she had normal liver test results. After three months, she presented with headache, fatigue, and intermittent low fever. Her laboratory tests showed a liver profile with a cholestatic pattern, and elevation of inflammatory parameters. Mesalamine was suspended, and an extensive study was performed. Cholangioresonance reported intra and extrahepatic bile duct dilation without obstruction, and thickening of the intrahepatic bile duct. She progressed with worsening of the liver profile without signs of liver failure. A liver biopsy was performed, which showed chronic non-suppurative cholangitis with granulomas and focal concentric fibrosis related to medium-caliber bile ducts, and IgG4 stain was negative.

Case Study of a 29 year-old Female with Ulcerative Proctitis

Our case report discusses SR a 29-year-old, physically active mother with weight - 150 lbs., height- 66 inches, and a BMI of 24. SR presented with a diagnosis of Ulcerative Proctitis of two years duration and with immediate need to address rectal bleeding (lower rectum and anus). No open wound, no hemorrhoids; only leaking fatigued tissue. Previous medications included mesalamine suppository prescribed when blood drainage was excessive -did not help extensively. Integrative planUlcerative Proctitis signifies inflammation, repair deficit and immune burden. This plan prioritizes reducing overall burden on the immune system, restoring healing and inducing repair. We used the LRA by ELISA/ACT® tests for delayed food and chemical sensitivities. This test was performed on February 5, 2021. Strong reactionsChicken, Sugar, Beet, Chamomile, FD & C Yellow # 6, D & C Green# 5, Locust Bean Gum, Benzyl Acetate, Parsnip Moderate reactionsPeanut, Carob, Swordfish, Geotrichum candidum, Toluene,Okra, RadishSR avoided the strong reactions for six months and moderate ones for three months- she discovered toluene in her lubricant! A supportive supplement regimen was also initiated – starting with the Ascorbate Vitamin C calibration (C cleanse) protocol. Other nutrients included a combination of L-carnitine, sulfur amino acids such as methionine, cysteine, and Omega 3 fats. SR continued the C cleanse weekly and took ~6 g buffered ascorbate daily. She also incorporated avocado in her diet to augment healthy fat intake.Eight months later there was already a significant decrease in blood loss. The LRA by ELISA/ACT test was repeated on October 16, 2021. Strong reactionsCow Dairy (group), Brewer's Yeast,1,2 Dichlorobenzene, Yogurt (Cow), Parsnip Moderate reactionsChocolate/Cocoa, Tuna, Processed Cheese (Cow), Mango, Eggplant, Tapioca, D & C Green #8, Benzopyrene, Beryllium Oxide, Isopropyl Ether, Catfish, Rapeseed/Canola Oil, Scallion/Spring Onion. Final outcomeThis second test showed a decrease in number of strong reactions, signaling improvement in immune tolerance. Omega 3 index close to 8% is healthy and SR's omega index increased to 7.38% and Omega 6/3 ratio improved to 4.8: 1.In 10 months

S123 Maternal and Fetal Outcomes After IBD Surgery During Pregnancy

Background: Inflammatory bowel disease (IBD) incidence peaks in the reproductive years. Despite advances in medical treatment, approximately 20% of ulcerative colitis (UC) and 80% of Crohn’s disease (CD) patients require surgical intervention during their lifetime. Active disease during pregnancy increases the risk of negative pregnancy outcomes, such as spontaneous abortion, low birth weight, prematurity and deformities. Achieving remission prior to conception and maintaining it throughout the pregnancy remain of utmost importance. However, surgery during pregnancy may be required for medically refractory disease or for disease-related complications such as intraabdominal abscess, perforation, or toxic megacolon. Literature pertaining to the maternal and fetal outcomes after IBD surgery during pregnancy remains scarce. Methods: This is a case series of 3 patients who underwent surgery for IBD during pregnancy and subsequently delivered at our quaternary IBD referral center. Results: Case 1: A 34-year-old female with recently diagnosed indeterminate colitis presented with disease exacerbation during her fifth gestational week. Despite treatment with mesalamine, methylprednisolone, and infliximab, she had persistent hematochezia, abdominal pain, and distention. On 11w6d of pregnancy, she underwent an open subtotal colectomy with end ileostomy for severe colitis. Postoperative period was uncomplicated. She then underwent a C-section at 38w5d of gestation. Baby weighed 2.9 kg, Apgar scores 9-9. The newborn had a cleft in the posterior soft palate, micrognathia, tongue tie, and laryngomalacia resulting in dyspnea and dysphagia, which required operative intervention during infancy. The mother ultimately underwent completion proctectomy with IPAA and ileostomy closure at 5- and 7-months following delivery, respectively. Postoperative pouch function was normal. During routine follow-up, pouchoscopy revealed cuffitis, which responded to mesalamine suppository. Case 2: A 28-year-old female with an 8-year history of UC previously treated with prednisone and azathioprine developed disease exacerbation during her 11th gestational week. During 25th week of pregnancy, she underwent an open subtotal colectomy with end ileostomy for acute severe ulcerative colitis. Postoperative period was uncomplicated. She underwent C-section at 39th week of gestation. Baby weighed 3.7 kg, Apgar scores 3-3-8. The newborn developed dyspnea which was resolved following positive pressure ventilation in the NICU for 30 hours. The mother underwent completion proctectomy with IPAA and ileostomy closure 2 years after delivery. Four years following pouch creation, she developed pouchitis, which was controlled with vedolizumab. Case 3: A 20-year-old female with recently diagnosed Crohn’s disease had disease exacerbation at 4 weeks gestation despite treatment with adalimumab and prednisone. A pelvic abscess was identified via ultrasound requiring percutaneous drainage twice. During the ninth week of pregnancy, she underwent a laparoscopic converted to open ileocecectomy due to recurrent abscess and abdominal pain. Postoperative period was uncomplicated. The pregnancy was complicated by pre-eclampsia in the third trimester. The patient had a vaginal delivery at 37w6d of gestation. Baby weighed 2.7 kg, Apgar scores 8-9. The post-delivery course of the mother and infant was uncomplicated. Conclusions: IBD affects females during their childbearing ages. IBD surgery at times needs to be done urgently/emergently; acceptable maternal and fetal outcomes can be achieved.

S2067 Mesalamine Hypersensitivity Induced Hemorrhagic Shock

Introduction: 5-Aminosalicylic acid (mesalamine) rarely induces hypersensitivity. It is first line therapy for treatment of ulcerative proctitis. However, the journal of gastroenterology and hepatology states 12% of patients are unable to tolerate mesalamine or other compounds of 5-aminosalicylic acid. The most common side effects are identified as headache, nausea, abdominal pain, and mild watery diarrhea. This case report highlights the importance of recognizing mesalamine hypersensitivity in patients with ulcerative colitis. Case Description/Methods: A 62-year-old man with history of hypertension, hyperlipidemia, chronic kidney disease stage 3B and ulcerative proctitis presented to the ED with abdominal pain (intensity 9/10), rectal pain, tenesmus, flatulence, persistent bloating, and bright red blood per rectum of 2 months duration. Colonoscopy showed diffuse moderate mucosal changes with congestion, erythema, friability, and loss of vascularity in the rectum extending in a contiguous fashion from 10 cm to anal canal. Pathology reported nonspecific chronic inflammation with hyperplastic epithelial changes but negative for dysplasia or malignancy. He began oral mesalamine and mesalamine suppository therapy. With symptomatic improvement he was discharged home and was readmitted 3 days later with worsening hematochezia. He began intravenous steroids and his mesalamine therapy was changed to balsalazide. During the next 24 – 48 hours, he started having increased hematochezia with blood clots associated with increased rectal pain (pain scale 10/10). His vital signs were recorded as temperature 97.3F, blood pressure 58/32, heart rate 42, respiratory rate 9 and saturation of 86% on room air. His hemoglobin dropped from 9.6 to 7.7. He was resuscitated with IV fluids and PRBC transfusion. His blood pressure and heart rate normalized. At that point he was diagnosed with 5-ASA hypersensitivity. All his mesalamine products were discontinued and hydrocortisone suppositories began with continuation of his IV steroids. He improved and was discharged home with a steroid taper and daily hydrocortisone suppositories (Figure 1). Discussion: 5-aminosalicylic acid (mesalamine) is currently the first line therapy for treatment of ulcerative proctitis. Although mesalamine hypersensitivity is not common, it is important to include it in the differential diagnoses of patients with pertinent inflammatory bowel disorders who present with worsening clinical symptoms after introduction to mesalamine or similar 5-aminosalicylic acid compounds.Figure 1.: A, CT A/P w/o IV contrast demonstrating edematous rectum with perirectal fat stranding suggesting proctitis. B, diffuse area of severely hemorrhagic and ulcerated mucosa in the rectum.

S2438 COVID-19: A Potential Trigger for Inflammatory Bowel Disease?

Introduction: Coronavirus Disease 2019 (COVID-19) has been shown to infect gastrointestinal tissues, and a wide variety of gastrointestinal manifestations have been described including alterations in the composition of the intestinal microbiome. Microbiome changes have been implicated in the pathogenesis of inflammatory bowel disease (IBD), but a clear relationship between viral infection and IBD has not been established. Case description/methods: Case 1 A 45-year-old woman presented to clinic with painless hematochezia and fecal urgency 2 weeks after developing anosmia and being diagnosed with COVID-19. She had a history of constipation but no other gastrointestinal problems. Her vital signs were normal and her exam was unremarkable. Her labs showed iron deficiency anemia with hemoglobin 10.2 and ferritin < 2. Colonoscopy showed 10cm of moderately friable rectal mucosa with erosions and loss of vascular pattern. Rectal pathology showed chronic active proctitis. She was diagnosed with ulcerative proctitis and treated with mesalamine suppositories with resolution of her symptoms. Case 2 A 48-year-old woman was admitted for five months of watery, bloody bowel movements that developed after an initial hospitalization for COVID-19 pneumonia. She reported 10-15 bowel movements daily, diffuse abdominal pain, nausea, and 10kg weight loss. She was initially diagnosed with C. difficile at another hospital but her symptoms did not improve with oral vancomycin. She was mildly tachycardic, but her exam was otherwise unremarkable. Labs showed hemoglobin 6.7, CRP 6.9, ESR 50, and fecal calprotectin 1880. C. difficile testing was negative. Colonoscopy showed pancolitis with moderate inflammation, edema, erosions, erythema, and friability most severe in the distal colon with ileal sparing. Pathology showed crypt architectural distortion and branching with cryptitis and crypt abscesses consistent with ulcerative colitis. After not responding to prednisone, she achieved clinical remission with infliximab. Discussion: Prior research has described the role of abnormal immune response to intestinal microbiota in the pathogenesis of IBD. Some studies have found an increased risk of IBD after infectious gastroenteritis, but no specific causal link has been demonstrated and the role of specific infections in the development of the dysregulated immune response is incompletely understood. These cases of new ulcerative colitis diagnosed after COVID-19 infection have implications for understanding potential viral triggers of IBD.

Suppository treatment in ulcerative proctitis

Ulcerative proctitis (UP) is a common form of ulcerative colitis (UC), the number of patients with UP is increasing. Suppository treatment containing mesalamine is usually the first-line choice for mild to moderate UP, here, we review the publications on mesalamine suppository in UP, to better understand its dosage, duration of therapy and adverse events in both induction and maintenance phases. We also review articles on budesonide, beclomethasone, tacrolimus, herbal medicine and acetarsol suppositories in UP, to present therapeutic strategies for patients with UP refractory to mesalamine suppository.

2055 A Case Report of Rectal Mesalamine-Induced Myopericarditis

INTRODUCTION: Inflammation of the pericardium, myocardium or both is a rare but known side effect of 5-aminosalicyclic acid (5-ASA) containing medications. While most reports in the literature of this side effect have occurred with oral mesalamine, our patient developed myopericarditis approximately 3 weeks after initiation of rectal mesalamine suppositories. CASE DESCRIPTION/METHODS: A 37-year-old man with a history of hypertension, GERD, irritable bowel syndrome and proctitis on rectal mesalamine suppositories presented to the emergency department with acute onset pleuritic chest pain and was found to have elevated troponin and non-specific ST segment changes on electrocardiogram. Initially he was evaluated for possible acute coronary syndrome; however given positional and respirophasic nature of the pain, his symptoms were felt to be more consistent with myopericarditis. Transthoracic echocardiogram showed a small pericardial effusion without tamponade and no significant wall motion abnormities. Cardiac MRI was consistent with myocarditis. Evaluation for infectious or autoimmune etiologies of myopericarditis was unrevealing, including negative ANA and Lyme antibody. He had been started on rectal mesalamine suppositories 3 weeks prior to presentation after colonoscopy showed proctitis concerning for possible ulcerative colitis. Later review of his colonoscopy findings and chronic gastrointestinal symptoms was more consistent with irritable bowel syndrome than ulcerative colitis. The rectal mesalamine was felt to be the most likely etiology of his myopericarditis and was stopped during the hospitalization. He was treated with a course of naproxen and colchicine with rapid resolution of chest pain. DISCUSSION: Myocarditis and pericarditis are well-described and potentially lethal side effects of drugs containing 5-ASA, although the mechanism for cardiac toxicity is not clear. Symptoms usually manifest within 28 days of drug initiation and may resolve with drug cessation alone. While the absorption of oral mesalamine is estimated to be around 20-45%, rectal mesalamine absorption is variable and likely depends of a variety of factors including retention time and degree of underlying rectal disease. Our case suggests that rectal absorption alone may be sufficient to cause cardiac toxicity and that rectal mesalamine may not be safe in patients who have previously had cardiac or other toxicity on oral 5-aminosalicyclic acid containing drugs.

Mesalamine Suppository Treatment in Crohnʼs Disease of the Pouch

Introduction: Mesalamine suppository is used to treat mild or moderate active left-sided colitis, pancolitis, or extensive colitis. However, there are no published data on its efficacy and safety in Crohn's disease (CD) of the pouch. Aim of this study was to evaluate the efficacy and safety of mesalamine suppository in patients with CD of the pouch. Methods: This case series included all patients with CD of the pouch from our prospectively maintained, IRB-approved Pouchitis Registry from 2007 to 2017. All patients were either actively taking mesalamine suppository or had used it in the past. Disease activity in pouch patients can be monitored using the modified Pouchitis Disease Activity Index (mPDAI) scores, consisting of symptom and endoscopy subscores. Pre- and post- treatment (minimum 6 months) pouchoscopy and clinical visits were used to calculate mPDAI symptom (range 0 - 6) and endoscopy (range 0 - 6) subscores. Analysis was performed using the paired nonparametric test, SPSS 22.0. Results: A total of 8 patients were included in this study, who underwent restorative proctocolectomy with ileal pouch anal anastomosis due to medical refractory ulcerative colitis (UC). The mean age at the time of pre-colectomy diagnosis of UC was 25.0±11.5 years. The mean current age was 46.1 ±15.3 years, with 4 (50.0%) being females, 1(12.5%) having smoked and 6 (75.0%) having used anti-tumor necrosis factor agents prior to mesalamine suppository use. The mean duration of mesalamine suppository use was 7.9±3.7 months. Patients on mesalamine suppository noted to have statistically significant lower mPDAI symptom subscores post treatment using univariate analysis (6.38±1.40 and 2.60±0.70, P = 0.011). Numerical improvement in endoscopy subscores was also noted with mesalamine suppository use. The pre- and post- treatment mean endoscopy subscores were 0.77±1.72 and 0.50±1.07 in the afferent limb (P =0.180); 1.56±1.94 and 1.13±1.80 (P =0.279) in the pouch body; and 2.00±1.87 and 1.75±1.98 (P =0.157) in the cuff, respectively. None of the patients experienced side effects throughout the therapy. Demographic and clinical data are depicted in Table 1. Treatment outcomes are demonstrated in Figure 1. Pouchoscopy images before (A) and after (B) mesalamine suppository therapy are shown in Figure 2.2815_A Figure 1. mPDAI symptom sub scores for 8 patients before & after Mesalamine suppository.2815_B Figure 2. Pouchoscopy before (A) and after (B) mesalamine suppository therapyConclusion: Our study suggests that Mesalamine suppository appears to be effective and safe in treating CD of the pouch.2815_C Figure 3. Demographic and Clinical Characteristics in patients with Crohn's Disease (CD) of the Pouch.

Budesonide Suppositories Are Effective and Safe for Treating Acute Ulcerative Proctitis

Although proctitis is the most limited form of ulcerative colitis, it causes unpleasant symptoms. Topical mesalamine, the standard treatment, is not always effective. We conducted a randomized phase 2 trial to determine the efficacy and safety of 2 doses of a budesonide suppository vs mesalamine suppositories vs combined budesonide and mesalamine suppositories for proctitis. We performed a prospective, double-blind, double-dummy, multicenter trial in 337 patients with active proctitis to compare the efficacies of 4 different suppository treatments. Patients were randomly assigned to groups given 2 mg budesonide suppositories (2 mg BUS; n= 89 patients), 4 mg BUS (n= 79), 1 g mesalamine suppositories (1 g MES; n= 81), or the combination of 2 mg BUS and 1 g MES (n= 88). The study was performed from November 2013 through July 2015 at 36 study sites in Europe and Russia. The primary end point was the time to resolution of clinical symptoms, defined as the first of 3 consecutive days with a score of 0 for rectal bleeding and stool frequency. The mean time to resolution of symptoms in the 4 mg BUS (29.8 days) and combination of 2 mg BUS and 1 g MES (29.3 days) groups resembled that of the standard 1 g MES treatment (29.2 days), but was significantly longer in the 2 mg BUS group (35.5 days). Furthermore, proportions of patients with deep, clinical, and endoscopic remission, as well as mucosal healing, were similar among the 1 g MES, 4 mg BUS, and combination therapy groups, but significantly lower in the group that received 2 mg BUS. No safety signals were observed, and the patients' treatment acceptance was high (67%-85% of patients). In a multicenter randomized trial, we found that the efficacy and safety of 4 mg BUS in treatment of active proctitis did not differ significantly from those of 1 g MES. Budesonide suppositories offer an alternative therapy to mesalamine for topical treatment of proctitis. Clinicaltrialsregister.eu no: 2012-003362-41.

Grandmaʼs Home Remedy: A Hydrogen Peroxide Enema You Should Not Try at Home

Introduction Hydrogen peroxide (H2O2) is known to cause colonic injury. H2O2 enemas were a home remedy commonly used to treat meconium ileus and fecal impaction. H2O2 is caustic to the colon and this practice was largely abandoned. Today, self-induced chemical rectal injuries are rare. We are presenting a patient with chemical proctitis secondary to H2O2 enema. Presentation A 34-year-old female with history of constipation presented to the ED with hematochezia for 3 days. The patient had 6 days of constipation before administering an enema of 100ml 3% H2O2 on her grandmother's advice. Immediately after she evacuated the enema and a large, painfully firm bowel movement followed by abdominal pain, cramping and diarrhea with hematochezia. She denied symptoms of systemic infection. Vital signs: BP 96/47, HR 69, RR 20, O2 sat 100% Room Air, Temp 37.4° C. Physical exam revealed a benign abdomen and rectal exam with tenderness but no visual abnormality. CT abdomen/pelvis with oral and intravenous contrast revealed diffuse wall thickening involving the rectum, likely representing proctitis. Free intraperitoneal air and venous or arterial thrombi were not visualized. Hematochezia, lower abdominal cramping, tenesmus and rectal pain continued. Poison control was contacted and instructed to treat as a lower GI bleed unless imaging showed arterial or venous air emboli in rectum or portal venous system. Treatment included IV fluids, morphine and clear liquid diet. Flexible sigmoidoscopy revealed diffuse severe inflammation characterized by erosions, erythema and shallow ulcerations in the rectum up to 10cm. Findings consistent with proctitis secondary to chemical insult. Biopsies showed small fragments of colonic mucosa with chronic inflammation, focal ulcer and mild lamina propria expansion with architectural distortion. Patient improved during admission and discharged with instructions for Mesalamine suppository for 30 days and outpatient follow up.FigureFigureFigureDiscussion Proctitis is the most common complication resulting from H2O2 enema. The damage is caused when H2O2 meets the H2O2 catalase resulting in microbubbles of oxygen which force the blood out of the intramural vasculature resulting in corrosive, lipid peroxidation and oxygen free radial injury. H2O2 enema can result in colonic gangrene, gas embolization and fulminant colitis which can be fatal. Precaution must be taken with home remedies to ensure they will be safe and effective to prevent injury and fatality.

Combined Restitutive Therapy for Treatment of Immunosuppressive Refractory Crohn Disease

Crohn’s Disease (CD) is believed to be the result of dys-regulated interactions between a genetically susceptible host and their commensal gut microbiota (1). CD affects over 600,000 Americans and treatment still faces many challenges (2). Pharmacotherapy centers on the use of anti-inflammatories and immunosuppressants (3). However, a sub-set of patients with CD are refractory to immunosuppressive therapy. Recent studies have implicated defects in autophagy and bacterial killing as a possible etiology leading to host-microbe dysregulation (4). This could explain the lack of response to immunosuppression seen in these CD patients. A recent study in adults with CD showed the potential for granulocyte-macrophage colony stimulating factor (GM-CSF) to enhance bacterial killing and restore intestinal homeostasis (5), but very little data exists in pediatric patients (6). Another study reports a role for low-dose naltrexone (LDN, a mu opioid antagonist) in helping restore the epithelial barrier in active CD (7). The mechanism of action of LDN is thought to be through activation of endogenous opioid signaling (8). Recent murine studies have shown that direct mu opioid receptor (MOR) activation can enhance intestinal epithelial healing and prevent epithelial apoptosis (9). Here, we report a combined intestinal-restitutive approach using GM-CSF and loperamide (a peripheral MOR agonist) to induce and maintain remission in a 17-year-old CD patient.

P-056 Effectiveness of Mesalamine Suppositories for Patients With Proctitis Unresponsive to High-dose (&gt;2.4 g) Oral Mesalamine

P-056 Effectiveness of Mesalamine Suppositories for Patients With Proctitis Unresponsive to High-dose (&gt;2.4 g) Oral Mesalamine

Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity

Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories.

Sa1135 Comparative Effectiveness of Initial Therapy for Ulcerative Proctitis in Real-World Clinical Practice: A Retrospective Study

Background: Ulcerative colitis is a common chronic inflammatory disease of the colon. In approximately 30% of patients, the disease is limited to the rectum as ulcerative proctitis (UP). While the principal medications used to treat UP have been studied extensively in randomized trials, their comparative effectiveness in real-world settings has been examined only in a few small head-to-head studies. This retrospective study examines the comparative effectiveness of oral 5-ASAs, mesalamine suppository (MS), and mesalamine enema (ME) as initial therapy for ulcerative proctitis. Methods: Using a large US integrated healthcare claims database, we identified all persons, aged ≥14 years, with evidence of newly diagnosed UP (ICD-9-CM 556.2, 556.3) between January 1, 2004 and December 31, 2008, based on: (1) ≥2 encounters with diagnoses of UP ≤90 days apart; (2) evidence of colonoscopy within 60 days of first encounter for UP (index visit); (3) evidence of receipt of either oral 5ASAs, MS, or ME as monotherapy on their index visit; and (4) no evidence of receipt of any pharmacotherapy for UP within 365 days preceding their index visit. Patients were followed for 365 days after their index visit for treatment of UP, especially evidence of treatment escalation (a proxy measure of the lack of effectiveness of initial therapy) and/or new encounters with diagnoses of more extensive disease (ICD-9-CM 556.X, excluding 556.2 and 556.3). We also examined total costs of pharmacotherapy for UP over this period. Results: We identified 548 patients with new onset UP who began monotherapy with oral 5-ASAs, MS, or ME. Mean (SD) age was 48 (16) years, and there were approximately equal numbers of men and women. Forty-five percent of patients were seen by a gastroenterologist at their index visit. At their index visit, 327 patients received MS as initial therapy; 138, an oral 5-ASA; and 83, ME. Men were more likely to have received oral 5-ASA as initial therapy than women. By day 90, 21% of patients receiving oral 5-ASAs as initial therapy had evidence of treatment escalation, compared with 9.5% of MS patients and 12% of ME patients; corresponding figures by day 365 were 34.1%, 20.8%, and 20.5%, respectively. By day 365, 9.8% of MS patients, 18.1% of ME patients, and 20.3% of oral 5-ASA patients had new encounters with evidence of more extensive disease. There were no differences in the mean numbers of emergency room visits or hospitalizations among the 3 groups. Mean total costs of pharmacotherapy for UP to day 365 in relation to initial therapy for UP were $526 for MS, $559 for ME, and $1251 for oral 5-ASAs. Summary & Conclusions: Our retrospective study confirms findings from the few existing head-to-head clinical trials that topical mesalamine (suppositories, enema) may yield better treatment outcomes than oral 5-ASAs as initial therapy for UP.

Solitary Rectal Ulcer Syndrome in Children and Adolescents

The aim of this study was to describe the presenting symptoms, endoscopic and histologic findings, and clinical courses of pediatric patients diagnosed with solitary rectal ulcer syndrome (SRUS). We describe 15 cases of SRUS diagnosed at our institution during a 13-year period. Cases were identified by review of a pathology database and chart review and confirmed by review of biopsies. Data were collected by retrospective chart review. Presenting symptoms were consistent but nonspecific, most commonly including blood in stools, diarrhea alternating with constipation, and abdominal/perianal pain. Fourteen of 15 patients had normal hemoglobin/hematocrit, erythrocyte sedimentation rate, and albumin at diagnosis. Endoscopic findings, all limited to the distal rectum, ranged from erythema to ulceration and polypoid lesions. Histology revealed characteristic findings. Stool softeners and mesalamine suppositories improved symptoms, but relapse was common. SRUS in children presents with nonspecific symptoms and endoscopic findings. Clinical suspicion is required, and diagnosis requires histologic confirmation. Response to present treatments is variable.

Development of testicular germ cell cancer following successful infliximab induction therapy for ulcerative colitis

Antitumor necrosis factor alpha (anti-TNFα) agents have substantially altered the management of inflammatory bowel diseases (IBD). Their benefits must however be weighed against increased risks for infections, lymphoma, and possibly other malignancies. We report on a 27-year-old man, with a six-year history of ulcerative colitis maintained on mesalamine suppositories, presenting with clinical, radiographic and biopsy evidence of an acute colitis flare. Due to the refractory nature of his disease, infliximab was started, resulting in induction of remission within six weeks. Three months after the first dose of infliximab, the patient was diagnosed with a testicular mixed germ cell tumor requiring orchiectomy. Four cases of testicular cancer development among patients using anti-TNFα agents have been identified. Given the prevalence of IBD in young men and recent suggestions for “top–down therapy,” testicular cancer as a potential complication of anti-TNFα agents should be further explored on a population basis.

Ulcerative Proctitis Patientsʼ Preferences for Topical Formulations of Mesalamine

Purpose: Ulcerative proctitis (UP) is a common inflammatory bowel disease associated with significant morbidity. Topical mesalamine (5-aminosalicylic acid; 5-ASA) reduces symptoms, disease flares, improves outcomes, and is considered first-line therapy. Dosing oral 5-ASA encumbers a large pill burden and carries increased risk of adverse events, but 5-ASA suppositories have low systemic absorption and fast onset of action (within days). Social factors have prevented patients from using rectal formulations. This study assessed patient perceptions and preferences for 5-ASA suppositories vs. enemas in the management of UP and potential effects of their use on compliance. Methods: Two phases of research were utilized. Phase 1, a qualitative study, used semi-structured, individual-depth methodology to explore UP treatment issues and validated questions asked in phase 2, an online survey of patients with UP on maintenance therapy. Results: Fourteen patients with UP and 21 gastroenterologists were interviewed in phase 1; 250 patients completed phase 2. Of these patients, 60% were female, 74% were Caucasian, 83% were 25-54 years old, and 57% perceived their UP as at least moderate severity. Symptoms (Table) were completely controlled in only 4% of patients despite oral 5-ASA maintenance therapy. Medication convenience was important; 84% of patients reported traveling during the past year, with 33% traveling >3 weeks/year. Patients experienced ˜6 UP flares over the past year. Forty percent of patients perceived their UP had not improved and 12% reported their UP had worsened since diagnosis. Of patients prescribed topical mesalamine, 62% would use a suppository without hesitation, while 38% would use an enema. Among patients who perceived their UP was worsening, >90% were willing to take a suppository compared with ˜50% willing to take an enema. Suppositories were rated by 90% of patients as clean or cleaner than enemas and 87% rated suppositories as being as discrete as or more discrete than enemas. Most patients (82%) reported that suppositories take the same or less time to administer than enemas and 86% rated suppositories as equal or superior to enemas in terms of portability. Conclusion: Mesalamine suppositories are a safe and well-accepted therapeutic option for patients with UP and may improve compliance compared with oral and enema formulations. This research was funded in part by Axcan Pharma Inc, QC, Canada. Disclosure: Dr Barrett and Herbert Swanson are employees of Axcan Pharma Inc. Dr Sanderson does not have a relevant financial relationship. This research was supported by an industry grant from Axcan Pharma.Table

A Multicenter, Randomized Study to Evaluate the Efficacy and Safety of Mesalamine Suppositories 1 g at Bedtime and 500 mg Twice Daily in Patients with Active Mild-to-Moderate Ulcerative Proctitis

A Multicenter, Randomized Study to Evaluate the Efficacy and Safety of Mesalamine Suppositories 1 g at Bedtime and 500 mg Twice Daily in Patients with Active Mild-to-Moderate Ulcerative Proctitis

Treatment of Newly Diagnosed Ulcerative Proctitis in Community-Based Practice

Purpose: Treatment of ulcerative proctitis (UP) is aimed at controlling inflammation and reducing symptoms. While orally administered 5-aminosalicylates (“5-ASAs”) traditionally have been the mainstay of acute and maintenance therapy for UP, 5-ASA suppositories or enemas are generally considered to be first-line therapy, due to evidence that they are more effective at inducing and maintaining remission. Little is known, however, about how UP is typically treated in community-based practice. Methods: Using a large US healthcare claims database, we identified all persons with evidence of newly diagnosed UP (ICD-9-CM 556.2, 556.3) between 1/1/2005 and 12/31/2007, based on: (1) ≥2 encounters for UP ≤90 days apart; (2) evidence of sigmoidoscopy/colonoscopy within 60 days of first visit for UP (“index date”); and (3) no evidence of receipt of any medication used to treat UP (eg, 5-ASA, glucocorticoid, etc.) in the year preceding index date. All patients were followed for 365 days from their index date. We examined pharmacotherapy for UP over post-index periods of 30 days and 365 days alternatively. Results: We identified a total of 518 patients with newly diagnosed UP. Mean (SD) age was 48 (16) years, and there were equal numbers of men and women. Forty-five percent of patients were seen by a gastroenterologist at initial visit. In the 30-day post-index period, 37% of patients had evidence of receipt of mesalamine suppository; 23%, an oral 5-ASA; 12%, mesalamine enema; 12%, rectal hydrocortisone; and 6%, oral prednisone. Antidiarrheals, antimetabolites, and TNF inhibitors were rarely used. Over the entire 365-day post-index period, the number of patients ever-prescribed 5-ASA suppositories increased to 45%; oral 5-ASAs, 38%; 5-ASA enemas, 18%; and systemic glucocorticoids, 20%. Combination and sequential treatment was frequent. Over 365 days, 24% of patients had evidence of receipt of both oral and rectal 5-ASAs; 11%, rectal 5-ASAs and rectal steroids; 2%, rectal 5-ASAs and budesonide; and 11%, rectal 5-ASAs and systemic steroids. Conclusion: While local therapy is commonly prescribed in patients with newly diagnosed UP, approximately one in four patients receive an oral 5-ASA preparation. In the year following diagnosis, one in five patients receive systemic steroids—a marker of failure of conservative therapy and/or disease progression. Our findings suggest that treatment of newly diagnosed UP by community-based physicians largely conforms to guidelines and recommendations. Support: This research was funded by Axcan Pharma Inc., which manufactures and markets a 5-ASA suppository (Canasa®). Disclosure: This research was funded by Axcan Pharma Inc., which manufactures and markets a 5-ASA suppository (Canasa®).